Article

Rebamipide, a gastro-protective and anti-inflammatory drug, promotes gastric ulcer healing following eradication therapy for Helicobacter pylori in a Japanese population: A randomized, double-blind, placebo-controlled trial

September 2007
Journal of Gastroenterology 42(8):690-3

DOI:10.1007/s00535-007-2076-2

Source
PubMed

Authors:

Akira Terano

Dokkyo University

Toshiro Sugiyama

Health Science University of Hokkaido

Hidekazu Suzuki

Tokai University

Show all 10 authorsHide

One week of Helicobacter pylori eradication therapy is insufficient for healing of gastric ulcers. We examined the efficacy of rebamipide in gastric ulcer healing following 1 week of eradication therapy in a randomized, double-blind, placebo-controlled trial. Patients with H. pylori-positive gastric ulcer were enrolled and received 1 week of eradication therapy, followed by 100 mg of rebamipide or placebo for 7 weeks. The primary end point was the gastric ulcer healing rate. Of the 309 patients entered in the trial, 301 completed H. pylori eradication therapy; 154 patients took rebamipide, and 147 took placebo. The healing rate in the rebamipide group was higher than that in the placebo group in the per-protocol analysis-80.0% (104/130) versus 66.1% (82/124) [95% confidence interval (CI), 3.1-24.7; P = 0.013)-and in a full analysis-70.1% (108/154) versus 60.5% (89/147) (95% CI, -1.1 to 20.3; P = 0.080). Compared with placebo, rebamipide significantly promoted gastric ulcer healing following 1 week of eradication therapy.

Peptic ulcer: the current state of the problem

Article

Apr 2022

Peptic ulcer disease (PUD) is a chronic polyetiological recurrent disease of gastroduodenal region. In most cases, the pathogenesis of PU is caused by imbalance between the aggressive factors and protective factors of the gastric or duodenal mucosa. Helicobacter pylori (H. pylori ) infection and the use of non-steroidal anti-inflammatory drugs (NSAIDs), including aspirin, are the major causative factors leading to PUD development. 65% of gastric ulcers and 80% of duodenal ulcers were found to be associated with H. pylori infection. In turn, NSAIDs account for 30% of gastric ulcers and 15% of duodenal ulcers. About 0.1–1% of all PUs are caused by Zollinger-Ellison syndrome. Abdominal pain is the leading symptom in the clinical findings of patients with exacerbation of PUD. Dyspeptic syndrome (vomiting, nausea, belching, abnormal bowel pattern) is much less common in patients with PUD. Endoscopic examination of the upper gastrointestinal tract is currently the gold standard test used in the diagnosis of PUD and is recommended for all patients suspected of having this disease (unless contraindicated). Antisecretory therapy including proton pump inhibitors is the main approach to the treatment of PUD, as well as the prevention of its complications. Integral to the treatment of patients with H. pylori -associated PU is the eradication therapy of the infection. It is reasonable to use a cytoprotector rebamipide, which accelerates ulcer healing and improves the resulting scar quality, as part of the pharmacotherapy of PUD. In addition, the use of rebamipide in H. pylori eradication therapy regimens contributes to increased efficiency of elimination of the microorganisms.

Diagnosis and Treatment of Peptic Ulcer in Adults (Clinical Guidelines of the Russian Gastroenterological Association, Russian Society of Colorectal Surgeons and the Russian Endoscopic Society)

Article

Full-text available

Apr 2020

Aim. These clinical recommendations present up-to-date methods for the diagnosis and treatment of peptic ulcer. The recommendations are intended for gastroenterologists and general practitioners.General provisions. Peptic ulcer (PU) represents a chronic relapsing disease occurring with alternating periods of exacerbation and remission. The main manifestation of the disease is the formation of a defect (ulcer) in the wall of the stomach and duodenum. Most cases of peptic ulcer are pathogenetically associated with the infection of H. pylori. PU can be an independent disease or represent symptomatic ulcers of the stomach and duodenum (medicinal, as a result of stress or endocrine pathologies, associated with chronic diseases of internal organs). In the absence of contraindications, esophagogastroduodenoscopy is recommended for all patients with suspected ulcer with the purpose of confirming the diagnosis. In order to determine indications for eradication therapy, all ulcer patients should be tested for the presence of H. pylori using a 13C-breath test or a stool antigen test. In the case of simultaneous endoscopy, rapid urease test can be used. For the prevention of subsequent relapses of ulcer, all PU patients with confirmed H. pylori should undergo eradication therapy. In addition, in order to achieve ulcer healing, 4–6 week antisecretory therapy with proton pump inhibitors is recommended. Clinical recommendations contain criteria for assessing the quality of medical care, an algorithm of the doctor’s actions, as well as information for patients.Conclusions. These clinical recommendations present modern ideas about the etiology and pathogenesis of peptic ulcer disease, its clinical manifestations, methods of laboratory and instrumental diagnostics and basic approaches to conservative and surgical treatment.

Diagnostics and treatment of Helicobacter pylori infection in adults: Clinical guidelines of the Russian gastroenterological association

Article

Full-text available

Feb 2018

Aim of publication. To present indications for antihelicobacter therapy, methods and sequence of diagnostics and eradication treatment of Helicobacter pylori (H. pylori) infection to general practitioners. Key points. Chronic gastritis caused by H. pylori infection, including that in «asymptomatic» patients can be considered to be an indication for H. pylori eradication therapy both as etiological treatment and opportunistic screening diagnostics for gastric cancer prevention. Indications for obligatory antihelicobacter therapy include stomach and a duodenum peptic ulcer (PU), stomach MALT-lymphoma, early gastric cancer with endoscopic resection. Breath test with 13С-labeled urea, laboratory test for assessment of anti-H. pylori antibodies in feces, rapid urease test and serological method can be recommended for primary diagnostics of infection. Serological test is not applicable after antihelicobacter therapy. According to the bulk of regional studies clarithromycin resistance level of H. pylori strains in Russia does not exceed 15%. Obtained data indicate the absence of high metronidazole-resistance of H. pylori as well as double resistance to clarithromycin and metronidazole. Standard triple therapy including proton pump inhibitor (PPI), clarithromycin and amoxicillin is recommended as first-line treatment for H. pylori eradication. Standard triple therapy should be carried out, applying various means that increase its efficacy. Alternatively to standard triple therapy, first-line eradication treatment may include four-component bismuth tripotassium dicitratebased therapy or non-bismuth quadrotherapy which includes PPI, amoxicillin, clarithromycin and metronidazole. Quadrotherapy with bismuth tripotassium dicitrate can also be applied as a basic mode of the second line treatment at inefficiency of standard triple therapy. Alternative mode of second line eradication treatment includes PPI, levofloxacin and amoxicillin. Levofloxacinbased triple therapy prescription in the presence of strict indications should be limited to gastroenterologists. The third-line eradication treatment is adjusted individually according to the history of previous treatment modes. Eradication efficacy may be increased by prolongation of treatment up to 14 days, applicaiton of modern PPIs or increase of PPI doze, addition of bismuth tripotassium dicitrate or probiotic. Conclusion. In each case of H. pylori detection it is reasonable to consider eradication therapy that is especially actual as H. pylori infection eradication is recognized as effective method of stomach cancer prevention. H. pylori eradication optimization methods can be applied both to standard and alternative modes while combination of these approaches allows to achieve the best result in a given patient.

Determination of the adequate dosage of rebamipide, a gastric mucoprotective drug, to prevent low-dose aspirin-induced gastrointestinal mucosal injury

Article

Full-text available

Nov 2016

Small intestinal mucosal injury caused by low-dose aspirin is a common cause of obscure gastrointestinal bleeding. We aimed to investigate the protective effects and optimal dose of rebamipide for low-dose aspirin-induced gastrointestinal mucosal injury. In this prospective randomized trial, 45 healthy volunteers (aged 20-65 years) were included and divided into three groups. The groups received enteric-coated aspirin 100 mg (low-dose aspirin) plus omeprazole 10 mg (Group A: proton pump inhibitor group), low-dose aspirin plus rebamipide 300 mg (Group B: standard-dose group), or low-dose aspirin plus rebamipide 900 mg (Group C: high-dose group). Esophagogastroduodenoscopy and video capsule endoscopy were performed, and the fecal occult blood reaction and fecal calprotectin levels were measured before and two weeks after drug administration. Although the fecal calprotectin levels increased significantly in Group A, they did not increase in Groups B and C. The esophagogastroduodenoscopic and video capsule endoscopic findings and the fecal occult blood test findings did not differ significantly among the three groups. In conclusion, standard-dose rebamipide is sufficient for preventing mucosal injury of the small intestine induced by low-dose aspirin, indicating that high-dose rebamipide is not necessary.

Efficacy and safety of 1-week Helicobacter pylori eradication therapy and 7-week rebamipide treatment after endoscopic submucosal dissection of early gastric cancer in comparison with 8-week PPI standard treatment: a randomized, controlled, prospective, multicenter study

Article

Aug 2014

Background: Endoscopic submucosal dissection (ESD) has been developed for early gastric cancer (EGC). Helicobacter pylori eradication therapy has been reported to have a preventive effect against metachronous recurrence of EGC after ESD. However, the efficacy and safety of eradication therapy on ESD-induced ulcer healing are not clear. In a randomized control study, we compared the standard therapy (8-week proton pump inhibitor) and eradication therapy combined with subsequent treatment with 7-week rebamipide for healing ESD-induced ulcers. Methods: A multicenter, randomized, open-label study was conducted. In group A, patients received 20 mg of omeprazole for 56 days. In group B, patients received 40 mg of omeprazole, 1,500 mg of amoxicillin, and 800 mg of clarithromycin for 7 days, and then 300 mg of rebamipide for 49 days. The primary end point was to evaluate the scarring ratio. Results: The scarring rate in group A was significantly higher than that in group B [85.0 % (34/40) vs. 56.8 % (21/37), P = 0.011]. The scarring rate of ulcers with an area ≥565.5 mm(2) in group A was significantly higher than that in group B [78.9 % (15/19) vs. 37.5 % (6/16), P = 0.018]. There was no significant difference between the groups in the scarring rate of smaller ulcers. No serious adverse events were observed in any of the patients in either group. Conclusion: H. pylori eradication therapy and 7-week rebamipide monotherapy were not superior to PPI monotherapy, but this combination therapy for smaller sized ulcers was an optimal therapeutic option for healing. Serious adverse events were not observed in either group.

Continuous co-prescription of rebamipide prevents upper gastrointestinal bleeding in NSAID use for orthopaedic conditions: A nested case-control study using the LIFE Study database

Article

Full-text available

Jun 2024
PLOS ONE

Background Rebamipide has been widely co-prescribed with non-steroidal anti-inflammatory drugs (NSAIDs) in Japan for decades. This study aimed to evaluate the effectiveness of rebamipide in preventing upper gastrointestinal bleeding in new users of NSAIDs without risk factors of NSAID-induced ulcers other than age. Methods A nested case-control study was conducted using medical claims data of 1.66 million inhabitants of 17 municipalities participating in Japan’s Longevity Improvement & Fair Evidence study. The cohort entry (t0) corresponded to a new user of NSAIDs for osteoarthritis or low back pain. Patients with risk factors of NSAID-induced ulcers other than age were excluded. Cases were defined as patients who underwent gastroscopy for upper gastrointestinal bleeding (occurrence date was defined as index date). A maximum of 10 controls were selected from non-cases at the index date of each case by matching sex, age, follow-up time, and type and dosage of NSAIDs. Exposure to rebamipide was defined as prescription status from t0 to index date: Non-user (rebamipide was not co-prescribed during the follow-up period), Continuous-user (rebamipide was co-prescribed from t0 with the same number of tablets as NSAIDs), and Irregular-user (neither Non-user nor Continuous-user). Conditional logistic regression analysis was conducted to estimate each category’s odds ratio compared to non-users. Findings Of 67,561 individuals who met the inclusion criteria, 215 cases and 1,516 controls were selected. Compared with that of Non-users, the odds ratios and 95% confidence interval were 0.65 (0.44–0.96) for Continuous-users and 2.57 (1.73–3.81) for Irregular-users. Conclusions Continuous co-prescription of rebamipide significantly reduced the risk of upper gastrointestinal bleeding in an Asian cohort of new users of NSAIDs with osteoarthritis or low back pain without risk factors other than age.

Syndrome of increased epithelial permeability in clinical practice. Multidisciplinary national Consensus

Article

Full-text available

Feb 2021

The purpose of the first multidisciplinary Consensus: to comprehensively analyze the pathophysiological, clinical, and pharmacotherapeutic aspects of the syndrome of increased epithelial permeability (SPEP) as one of the basic mechanisms of the development of human pathology. The Consensus presents the structure of the three main levels of cytoprotection: preepithelial, epithelial and subepithelial, and the structure of intercellular tight contacts in epithelial tissues and endothelium is considered in detail. The clinical sections of the Consensus are devoted to the role of SPEP in diseases of the digestive system, cardio-cardiovascular and other visceral systems. A separate section summarizes the materials illustrating the significant role of SPEP in mental disorders and diseases of the nervous system. A separate chapter of the Consensus is devoted to cytoprotective therapy in SPEP. Cytoprotective effects of such proton pump inhibitor as rabeprazole, bismuth preparations and probiotics have been shown. Special attention is paid to the clinical and pharmacological specialties of the cytoprotector of rebamipide. Clinical the effectiveness of rebamipide shown as in functional, so in organic lesions of the digestive system. Its anti-cancer preventive effects are of practical importance. © 2021 Vserossiiskoe Obshchestvo Kardiologov. All rights reserved.

Rebamipide: Evidence base for use in gastroenterology

Article

Full-text available

Dec 2020

Rebamipide is a cytoprotective drug that has been used in practical gastroenterology for 30 years. This article summarizes the main results of the most relevant clinical studies of rebamipide in diseases of various parts of the gastrointestinal tract, including the esophagus, stomach, small and large intestine.

Pharmacological and clinical feature of rebamipide: New therapeutic targets

Article

Full-text available

Apr 2020

Rebamipide is a cytoprotector developed in Japan where it has been successfully used for the treatment of stomach diseases for 30 years. Initially discovered effects of the drug included the induction of prostaglandins and the elimination of free oxygen radicals. Recent studies discovered new therapeutic targets of the drug, its new forms that made possible using rebamipid for the treatment of such diseases as NSAID enteropathy, ulcerative colitis, radiation colitis, pouchitis, enteropathy with impaired membrane digestion. It is used in endoscopy, ophthalmology, chemotherapy, rheumatology. The aim of this review is to present current information about the pharmacological and clinical feature of rebamipide and to study its therapeutic potential.

Rebamipide potentially mitigates methotrexate‐induced nephrotoxicity via inhibition of oxidative stress and inflammation: A molecular and histochemical study

Article

Full-text available

Jul 2020
ANAT REC

Methotrexate (MTX) is a widely used chemotherapeutic agent; nevertheless, the nephrotoxicity associated with its use has limited its clinical use. Rebamipide (REB) is a gastro‐protective agent with diverse promising biological activities. Here, we investigated the renoprotective effects of REB against MTX‐induced nephrotoxicity in rats. Male Wistar rats were allocated into four groups: the normal control group, the REB group (100 mg kg⁻¹ day⁻¹, PO, for 12 days), the MTX group (which received a single injection of 20 mg/kg, ip), and the REB + MTX group (which received 100 mg kg⁻¹ day⁻¹ REB for 7 days before and 5 days after being injected with 20 mg/kg MTX). Interestingly, MTX triggered kidney injury, characterized by renal dysfunction along with histopathological alterations. Moreover, increased reactive oxygen species level and inflammatory response were detected in the kidney of MTX‐treated rats. However, REB prevented MTX‐induced oxidative kidney injury and boosted an antioxidant balance. Mechanistically, REB markedly activated the NRF‐2 protein and upregulated the expression of both SIRT‐1 and FOXO‐3 genes. Additionally, REB administration strongly inhibited the inflammatory response by downregulating both NF‐κB‐p65 and TLR‐4. Finally, the coadministration of REB and MTX activated the mTOR/PI3K/AKT signaling pathway. Simultaneously, REB treatment attenuated the reduction in glomerular size, the widening of the capsular spaces, and the tubular cell damage due to MTX administration. Taken together, these results indicate the potential of REB as adjuvant therapy to prevent nephrotoxicity in patients receiving MTX treatment.

New Prospects of Cytoprotection in the Treatment and Prevention of Gastric and Intestinal Diseases (Resolution of an Expert Council and Literature Review)

Article

Full-text available

May 2020

Aim. To generalize up-to-date information on the possibilities of cytoprotection in the treatment and prevention of gastric and intestinal diseases, as well as to present the materials of an Expert Council meeting held on February 8, 2020 in Moscow under the support of the Alium company. General provisions. The conducted Expert Council meeting was aimed at discussing the importance of improving the cytoprotective properties of the gastric and intestinal mucous membrane in the treatment of its lesions. It was shown that Rebamipide exhibits positive effects on various parts of the protective barrier of the gastrointestinal tract (GIT), primarily due to its stimulating action on the production of prostaglandins playing a key role in maintaining the cytoprotective properties of the gastrointestinal mucosa. The possibilities of applying Rebamipide for the treatment and prevention of erosive and ulcerative gastrointestinal lesions caused by non-steroidal anti-inflammatory (NSAIDs) and antithrombotic drugs were demonstrated. In the treatment of gastroesophageal reflux disease, Rebamipide is recommended for patients refractory to therapy with proton pump inhibitors (PPIs) and for those with non-acid reflux. The efficacy of Rebamipide in the treatment of Helicobacter pylori ( H.pylori ) infection, as well as functional dyspepsia and chronic gastritis, was confirmed. Conclusions.Rebamipid is a highly effective drug positively affecting various cytoprotection links, thus being suitable for the treatment and prevention of erosive and ulcerative lesions of the gastrointestinal tract, as well as gastroenterological diseases of various etiologies. Conflict of interest: The Expert Council meeting was supported by the Alium company.

Gastroprotection in the treatment of erosive and ulcerative lesions of the stomach and small intestine

Article

Mar 2020

In article the reasons of erosive and ulcer injuries of a stomach, a small intestine are described. Special attention is paid to intake of nonsteroid anti-inflammatory medicines, microcirculation violation. Side effects of nonsteroid anti-inflammatory medicines and inhibitors of a proton pomp are in detail considered. Groups of patients with erosive and ulcer injuries of a stomach, small intestine with dyspepsia to which purpose of inhibitors of a proton pomp is not shown are allocated. Rebamipide can be appointed for prevention and treatment of erosive and ulcer injuries of a stomach, a small intestine with dyspepsia, both with inhibitors of a proton pomp, and in the form of monotherapy for the purpose of a gastroprotection to patients when use of inhibitors of a proton pomp is inexpedient. The gastroprotection algorithm depending on a condition of a gastric acid secretion of patients is offered.

Cytoprotective therapy in the modern gastroenterology: the role and place of the rebamipide

Article

Feb 2020

I. M. Skrypnyk

Оглядова стаття присвячена проблемам лікування та профілактики захворювань органів травлення із застосуванням цитопротектора ребаміпіду, який стимулює продукцію ендогенних простагландинів у слизовій оболонці шлунка і тонкої кишки, прискорюючи загоєння ерозивно‑виразкових уражень, виразкових уражень, спричинених Нelicobacter pylori, прийомом стероїдів і нестероїдних протизапальних засобів. Основними властивостями ребаміпіду є підвищення синтезу простагландинів і захисних глікопротеїнів (фукопротеїнів), пригнічення процесів перекисного окиснення ліпідів, запальних цитокінів. Призначення комбінації інгібітора протонної помпи і цитопротектора ребаміпіду на тлі хіміотерапії дає змогу підвищити резистентність слизового бар’єра, зменшити вираженість процесів вільнорадикального окиснення та метаболічної інтоксикації і може вважатись ефективним методом профілактики ерозивно‑виразкових уражень гастродуоденальної зони у хворих на гострі лейкемії в динаміці цитостатичного лікування.Прямий зв’язок ризику розвитку раку шлунка з тяжкістю і ступенем атрофічного гастриту, кишкової метаплазії і дисплазії, відсутність зворотного розвитку кишкової метаплазії і дисплазії на тлі ерадикації H. pylori передбачає використання в якості засобів первинної і вторинної профілактики препаратів гастропротективної дії. Ребаміпід — високоефективний і безпечний засіб первинної та вторинної профілактики раку шлунка завдяки антигелікобактерному ефекту, протизапальній дії, здатності відновлювати клітинну структуру епітелію шлунка. Перевагою ребаміпіду порівняно з іншими цитопротекторами є доведена його додаткова дія на слизову оболонку тонкої та товстої кишки.

Consenso mexicano sobre diagnóstico, prevención y tratamiento de la gastropatía y enteropatía por antiinflamatorios no esteroideos

Article

Full-text available

Feb 2020

More than 30 million persons worldwide take nonsteroidal anti-inflammatory drugs (NSAIDs) on a daily basis, and annual consumption is increasing. In addition to their analgesic and anti-inflammatory properties, NSAIDs also produce well-known gastrointestinal adverse events. There is no consensus in Mexico on the diagnosis, treatment, and prevention of NSAID-induced gastropathy and enteropathy, and so the Asociación Mexicana de Gastroenterología brought together a group of experts to establish useful recommendations for the medical community. Thirty-three recommendations were formulated in the present consensus, highlighting the fact that the risk for NSAID-induced gastrointestinal toxicity varies according to the drug employed and its pharmacokinetics, which should be taken into account at the time of prescription. The risk factors for gastroduodenal complications due to NSAIDs are: a history of peptic ulcer, age above 65 years, high doses of NSAIDs, Helicobacter pylori infection, and the presence of severe comorbidities. The symptoms and gastroduodenal damage induced by NSAIDs vary, ranging from an asymptomatic course to the presentation of iron-deficiency anemia, bleeding, stricture, and perforation. Capsule endoscopy and enteroscopy are direct diagnostic methods in NSAID enteropathy. Regarding prevention, the minimum dose of an NSAID needed to achieve the desired effect, administered for the shortest period of time, is the recommendation. Finally, proton pump inhibitors are the gold standard for the prophylaxis and treatment of gastroduodenal effects, but they are not useful in enteropathy. Copyright © 2020 Asociación Mexicana de Gastroenterología. Publicado por Masson Doyma México S.A. All rights reserved.

Efficacy and safety of the use of rebamipide in the scheme of triple eradication therapy of Helicobacter pylori infection: A prospective randomized comparative study

Article

Full-text available

Aug 2018

Purpose of the study. To evaluate the effectiveness and safety of the use of rebamipide as part of the triple eradication therapy (ET) scheme of Helicobacter pylori infection. Materials and methods. A prospective, randomized comparative study included 94 patients with uncomplicated H. pylori-associated stomach/duodenal ulcer. In the process of randomization, patients are divided into three groups depending on the intended therapy. The first group (n=36) received a classical triple scheme of the first-line ET (omeprazole 20 mg twice a day, amoxicillin 1000 mg twice a day, clarithromycin 500 mg twice a day) for 10 days. Patients of the second group (n=33) were assigned a classical triple scheme of ET with the inclusion of rebamipide (omeprazole 20 mg twice a day, amoxicillin 1000 mg twice a day, clarithromycin 500 mg twice a day, rebamipide 100 mg 3 times a day day) for 10 days. Patients of the third group (n=25) were assigned a classical triple scheme of ET with the inclusion of rebamipide (omeprazole 20 mg twice a day, amoxicillin 1000 mg twice a day, clarithromycin 500 mg twice a day, rebamipide 100 mg 3 times a day) in for 10 days, with the prolongation of the administration of rebamipide for the next 20 days. The effectiveness of ET was determined by the respiratory test after 6 weeks after the end of treatment. Adverse events were recorded by patients in specially developed diaries. All patients with gastric ulcer at the 6th week underwent a histological examination of the biopsy specimens of the antrum and the body of the stomach, assessing the inflammatory activity of the process on a point system in accordance with the updated Sydney system. Results and discussion. Efficiency of H. pylori eradication in the first group was 77.7% (ITT), 82.3% (PP), in the second group - 81.8% (ITT), 84.4% (PP), and in the third group - 84% (ITT), 87.5% (PP). The use of rebamipide in the triple ET regimen was associated with an increase in H. pylori eradication efficiency, both with simultaneous use with the scheme [odds ratio (OR) 1.16; 95% confidence interval (CI) 0.32-4.24], and with subsequent prolonged admission (OR 1.5, 95% CI 0.34-6.7). A somewhat more pronounced dynamics of the epithelization of erosive and ulcerative changes in the mucous membrane of the stomach and duodenum to the 21st and 28th days in the third group of patients was noted. The incidence of adverse events between the groups was comparable: 22.2% in the first group, 24.2% in the second group and 20% in the third group. In the pathomorphological evaluation of biopsy specimens of patients with gastric ulcer at the 6th week after the treatment, significant differences were revealed between the first and third groups in terms of the inflammatory activity in the antrum stomach (2±0.63 vs. 1.4±0.52; p=0,0399). The conclusion. The inclusion of rebamipide in the classical triple scheme of H. pylori ET increases the effectiveness of treatment and does not affect the safety profile. In the post-eradication period, it is advisable to continue the use of rebamipide to potentiate the repair of the gastric mucosa and regress the inflammatory processes.

The role of mucoprotective agents in endoscopic submucosal dissection‐derived ulcers: a systematic review

Article

Full-text available

Jun 2018

Background Currently, it is still unclear whether adding a mucoprotective agent to a Proton Pump Inhibitor (PPI) results in better outcomes compared to using a PPI alone in patients with post‐gastric endoscopic submucosal dissection (ESD) ulcers. This study aimed to examine the efficacy of PPI alone versus combination treatment in healing of post‐gastric ESD ulcers, as well as on delayed bleeding and amount of blood transfused. Methods A systematic search of MEDLINE, EMBASE, Cochrane, and ISI Web of knowledge databases, up until May 2017, for randomized trials comparing PPI alone versus PPI plus a mucoprotective drug in achieving ulcer healing in patients undergoing gastric ESD was performed. The primary outcome is scarring stage on endoscopic assessment at 4 or 8 weeks after gastric ESD. Results From an initial 3071 citations, eight articles (n= 953 lesions from 934 patients) were analysed. Patients receiving combination treatment achieved a scarring stage significantly more often than those on a PPIs alone at 4 or 8 weeks after ESD, (RR=1.36, 95% CI; 1.06‐1.75). No study reported amount of blood transfused. There were no significant between treatment‐group differences in terms of delayed bleeding (RR= 0.58, 95% CI; 0.17‐1.99). Neither location of ulcer nor H.pylori infection was related to ulcer scarring stage. Conclusion The limited evidences suggested combination treatment may be more effective in accelerating the process of ulcer healing in patients undergoing gastric ESD than the use of PPI alone, but does not appear to alter delayed bleeding risk.

Evaluation of efficacy and safety of rebamipide use in the triple therapy for Helicobacter pylori eradication: a pilot study

Article

Full-text available

Apr 2018

The article presents the results of a pilot prospective randomized study aimed at evaluating the efficacy and safety of rebamipide (Rebagit, PRO.MED.CS Praha a.s., Czech Republic) as part of the triple therapy for helicobacter pylori (H. Pylori) eradication. 54 patients with H. pylori-associated gastric ulcer/duodenal ulcer were enrolled to the study. All patients were randomized to two therapeutic groups depending on the eradication therapy to be received. Group 1 received the standard triple therapy, Group 2 received the standard triple therapy plus rebamipide. The efficacy of H. pylori eradication in Group 1 amounted to 78,2% (ITT), 81,8% (PP), and in Group 2 to 83,8% (ITT), 86,6% (PP). Odd ratio of efficient eradication with the use of rebamipide as part of standard triple therapy for helicobacter pylori eradication was 1,44 (95 CI: 0,36–5,72). The side effect rates between the groups were comparable

Possibilities for optimization of eradication therapy for Helicobacter pylori infection in modern clinical practice

Article

Full-text available

Feb 2017

A steady decline in the effectiveness of standard eradication therapy (ET) regimens for Helicobacter pylori infection necessitates a search for ways of their optimization, by enhancing the efficiency of treatment protocols and by improving their safety and tolerability. The review systematizes the data available in the literature on main accessible methods for optimizing ET regimens. Among the optimization methods that can considerably enhance the efficiency of ET regimens, one may identify their addition of a bismuth agent (by 10-20%), the use of rebamipide (by 11.9%), adjuvant therapy with probiotics (by 8.1-13%), or doubledose proton pump inhibitors (by 8%). Only adjuvant therapy with probiotics results in a significant decrease in the incidence of side effects from ET. In posteradication period, rebamipide should be used to potentiate gastric mucosal repair and to regress inflammatory processes.

Rebamipide ameliorates atherosclerosis by controlling lipid metabolism and inflammation

Article

Full-text available

Feb 2017
PLOS ONE

Atherosclerosis is a chronic inflammatory disease caused by the accumulation of excess lipid in the aorta and the severity is regulated by T lymphocytes subsets. Rebamipide has therapeutic activity in collagen induced arthritis (CIA) by controlling the balance between T helper (Th) 17 and regulatory T (Treg) cells. In this study, we aimed to determine whether rebamipide reduces the development of atherosclerosis. To investigate the therapeutic effect of rebamipide, ApoE-KO mice fed a western diet were administered rebamipide orally for 8 weeks. Mice were sacrificed followed by the evaluation of plaque formation in the aorta or immunohistochemistry for IL-17 and Foxp3. Serum was also prepared to determine the pro-inflammatory cytokine levels. The ability of rebamipide to regulate lipid metabolism or inflammation was confirmed ex vivo. Results The oral administration of rebamipide decreased plaque formation in atherosclerotic lesions as well as the markers of metabolic disorder in ApoE-deficient mice with atherosclerosis. Pro-inflammatory cytokines were also suppressed by rebamapide. In addition, the population of Th17 was decreased, whereas Treg was increased in the spleen of rebamipide-treated ApoE deficient mice. Rebamipide also ameliorated the severity of obese arthritis and has the capability to reduce the development of atherosclerosis by controlling the balance between Th17 and Treg cells. Thus, rebamipide could be a therapeutic agent to improve the progression of inflammation in metabolic diseases.

CLINICAL AND PHARMACOLOGICAL CHARACTERISTICS OF THE USE OF REBAMIPIDE IN DISEASES OF THE GASTROINTESTINAL TRACT LITERATURE REVIEW

Article

Full-text available

Dec 2016

NSAID-induced lesions of the gastrointestinal tract gained wide spread in the recent decade. Their range includes lesion of the esophagus, syndrome of dyspepsia, gastropathy and enteropathy. Diagnosis establishment of enteropathy is complicated and became possible after introduction of the capsule endoscopy. PPI are used for treatment of gastropathy, but they are not effective for treating enteropathy. Cytoprotective prostaglandins play the key role in the development of NSAID lesions of the gastrointestinal tract. Synthetic analogues of prostaglandins of misoprostol type possess cytoprotective action, but cause a significant number of adverse events. Rebamipide, a new gastroprotective agent in Russia stimulates production of endogenous prostaglandins. This drug proved its efficacy during the clinical trials performed according to the standards of the evidence-based medicine.

REBAMIPIDE: EFFECTIVE DRUG PREVENTION OF NSAID ENTEROPATHY IS POSSIBLE

Article

Full-text available

Dec 2016

Prevention of gastrointestinal tract (GIT) complications is the most important element for the rational use of nonsteroidal anti-inflammatory drugs (NSAIDs) and low-dose aspirin (LDA). Proton pump inhibitors (PPIs) have long been the only medication to prevent these complications. However, PPIs are only effective in preventing and treating upper GIT diseases (NSAID gastropathy) rather than small intestinal injury (NSAID enteropathy). Rebamipide has emerged as a novel agent to protect the gastrointestinal mucosa today. The effect of the drug differs from that of PPIs: it is a typical gastroand enteroprotector that enhances the synthesis of endogenous prostaglandins and possesses a significant anti-inflammatory potential. Rebamipide has long been widely used by doctors inJapan,South Korea, andChinaas an effective and safe agent for the treatment of many diseases of the digestive system. There is a strong evidence base for the efficacy of rebamipide in preventing and treating NSAID gastropathy and NSAID enteropathy (including LDA-induced injuries). Controlled studies have found that the drug is not inferior to the classic gastroprotective agent misoprostol, significantly outperforming the latter in its tolerability. This review describes the mechanism of action of rebamipide and main clinical trials of its therapeutic effect in NSAID gastropathy and NSAID enteropathy.

Rebamipide: New opportunities of gastroenteroprotection

Article

Full-text available

Dec 2015

This review paper deals with the prevention and therapy of nonsteroidal anti-inflammatory drug (NSAID)-induced gastrointestinal mucosal injuries in patients with disease of the cardiovascular and locomotor systems. Particular emphasis is laid on the new Russian drug rebamibide that is a stimulant of prostaglandin and glycoprotein synthesis and an inhibitor of the synthesis of oxidative stress products, inflammatory cytokines, and chemokines in the gastrointestinal mucosa. The advantage of rebamipide over classical gastroprotectors is its proven additional effect on the small and large intestinal mucosa. This drug has been registered and is actively used in a number of countries, including Japan, South Korea, and China.

Rebamipide does not protect against naproxen-induced gastric damage: A randomized double-blind controlled trial

Article

Full-text available

Jun 2016
BMC GASTROENTEROL

Background Rebamipide is a gastroprotective agent with promising results against gastric damage induced by non-steroidal anti-inflammatory drugs. The present study evaluated if rebamipide protects against naproxen-induced gastric damage in healthy volunteers. Changes in gastric PGE2 tissue concentration were also evaluated. Methods After a preliminary endoscopy to rule out previous gastric macroscopic damage, twenty-four healthy volunteers of both sexes were divided into 2 groups. One group received sodium naproxen 550 mg b.i.d. plus placebo for 7 days, while the other group received sodium naproxen 550 mg b.i.d. plus rebamipide 100 mg b.i.d. At the end of treatment, a new endoscopy was performed. Gastric macroscopic damage was evaluated by the Cryer score and by the modified Lanza score. The primary outcome measure of the trial was the macroscopic damage observed in each treatment group at the end of treatment. Biopsies were collected at both endoscopies for PGE2 quantification and histopathological analysis (secondary outcomes). Tissue PGE2 was quantified by ELISA. The randomization sequence was generated using 3 blocks of 8 subjects each. Volunteers and endoscopists were blind to whether they were receiving rebamipide or placebo. ResultsAll recruited volunteers completed the trial. Sodium naproxen induced gastric damage in both groups. At the end of the study, median Cryer score was 4 in both groups (Difference = 0; 95%CI = −1 to 0; p = 0.728). In the placebo group, the mean tissue PGE2 concentration was 1005 ± 129 pg/mL before treatment and 241 ± 41 pg/mL after treatment (p < 0.001). In the rebamipide group, the mean tissue PGE2 concentration was 999 ± 109 pg/mL before treatment, and 168 ± 13 pg/mL after treatment (p < 0.001). There was no difference in mean tissue PGE2 between the two groups (difference = 5; 95%CI from −334.870 to 345.650; p = 0.975). No significant change was observed at the histopathological evaluation, despite the evident macroscopic damage induced by naproxen. Conclusion Rebamipide does not protect against naproxen-induced gastric damage in healthy volunteers. Trial registrationClinicalTrials.gov, NCT02632812. Registered 14 December 2015.

Evidence-based clinical practice guidelines for peptic ulcer disease 2015

Article

Feb 2016

The Japanese Society of Gastroenterology (JSGE) revised the evidence-based clinical practice guidelines for peptic ulcer disease in 2014 and has created an English version. The revised guidelines consist of seven items: bleeding gastric and duodenal ulcers, Helicobacter pylori (H. pylori) eradication therapy, non-eradication therapy, drug-induced ulcer, non-H. pylori, non-nonsteroidal anti-inflammatory drug (NSAID) ulcer, surgical treatment, and conservative therapy for perforation and stenosis. Ninety clinical questions (CQs) were developed, and a literature search was performed for the CQs using the Medline, Cochrane, and Igaku Chuo Zasshi databases between 1983 and June 2012. The guideline was developed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system. Therapy is initially provided for ulcer complications. Perforation or stenosis is treated with surgery or conservatively. Ulcer bleeding is first treated by endoscopic hemostasis. If it fails, surgery or interventional radiology is chosen. Second, medical therapy is provided. In cases of NSAID-related ulcers, use of NSAIDs is stopped, and anti-ulcer therapy is provided. If NSAID use must continue, the ulcer is treated with a proton pump inhibitor (PPI) or prostaglandin analog. In cases with no NSAID use, H. pylori-positive patients receive eradication and anti-ulcer therapy. If first-line eradication therapy fails, second-line therapy is given. In cases of non-H. pylori, non-NSAID ulcers or H. pylori-positive patients with no indication for eradication therapy, non-eradication therapy is provided. The first choice is PPI therapy, and the second choice is histamine 2-receptor antagonist therapy. After initial therapy, maintenance therapy is provided to prevent ulcer relapse.

Factors associated with healing of artificial ulcer after endoscopic submucosal dissection with reference to Helicobacter pylori infection, CYP2C19 genotype, and tumor location: Multicenter randomized trial

Article

Sep 2015
DIGEST ENDOSC

The healing speed of peptic ulcer is affected by a number of factors, including Helicobacter pylori (H. pylori) infection and intragastric pH. Acid inhibition exerted by proton pump inhibitors differs by CYP2C19 genotypes. Here, we investigated whether the healing speed of artificial ulcers formed after endoscopic submucosal dissection (ESD) was influenced by H. pylori infection, CYP2C19 genotypes, or other factors. A total of 96 H. pylori-positive patients with gastric tumors scheduled for ESD were randomly assigned to receive eradication therapy for H. pylori before ESD (pre-ESD eradication) (n = 44) or after (post-ESD eradication) (n = 52). Patients received eradication therapy consisting of lansoprazole 30 mg, amoxicillin 750 mg, and clarithromycin 200 mg twice daily for 1 week. After ESD, lansoprazole 30 mg was administered once daily for 8 weeks. Ulcer size was endoscopically measured on the next day and at 4 and 8 weeks after ESD. Mean reduction rate of artificial ulcer area in the pre-ESD eradication group was 94.7% ± 5.5% at 4 weeks, which was similar to that in the post-ESD eradication group (94.7% ± 6.7%, p = 0.987), irrespective of CYP2C19 genotypes. In multivariate analyses, the location of the gastric tumor (middle and upper, odds ratio: 4.05, 95% confidence interval: 1.620-10.23, p = 0.003) was a factor for 97% reduction of artificial ulcer area at 4 weeks post-ESD, but CYP2C19 genotypes and H. pylori infection were not. The healing speed of ESD-induced artificial ulcer was affected by tumor location, but not time of H. pylori eradication, resected size, or CYP2C19 genotypes. This article is protected by copyright. All rights reserved.

Effective healing of endoscopic submucosal dissection-induced ulcers by a single week of proton pump inhibitor treatment: A retrospective study

Article

Full-text available

Apr 2015
BMC Res Notes

Although artificial ulcers generally heal faster than Helicobacter pylori-related or nonsteroidal anti-inflammatory drug-related peptic ulcers, endoscopic submucosal dissection (ESD)-induced gastric ulcers are usually treated with a proton pump inhibitor (PPI) for 4-8 weeks. The effect of oral administration of a PPI for 1 week on ESD-induced gastric ulcers has not yet been evaluated. In the present study, we evaluated the efficacy of oral PPI for 1 week in patients with ESD-induced ulcers. We selected 45 patients who underwent ESD for gastric mucosal tumors between June 2005 and July 2006 at Toyama University Hospital, and who met our inclusion criteria. All patients received omeprazole intravenously for 2 days after ESD and then orally for 1 week to prevent bleeding. Twenty two patients received no further omeprazole therapy (1-week group) and the rest received omeprazole orally for 7 more weeks (8-week group). Follow-up endoscopy was performed at 1 day, 4 weeks, and 8 weeks after ESD. We compared the ulcer healing rates between both groups. There were no significant differences between the groups in the ulcer-healing rate, because ulcers healed in 22 (96%) and 20 (91%) patients from the 8-week and 1-week groups, respectively. In our study, oral administration of omeprazole for 1 week was sufficient to achieve healing of ESD-induced artificial gastric ulcers. A larger prospective trial will be required to confirm these findings.

GC-MS and LC-MS analysis of Kakadu plum fruit extracts displaying inhibitory activity against microbial triggers of multiple sclerosis

Article

Full-text available

Apr 2015

Introduction: Multiple sclerosis is an autoimmune disease which can be triggered in genetic susceptible individuals by Acinetobacter spp. and Pseudomonas aeruginosa infections. Terminalia ferdinandiana (Kakadu plum) fruit has documented therapeutic properties as a general antiseptic agent. Extracts prepared from the leaves have also been shown to block several microbial triggers of autoimmune inflammatory diseases. This study examines the ability of Kakadu plum fruit extracts to inhibit some microbial triggers of multiple sclerosis. Methods: T. ferdinandiana fruit solvent extracts were investigated by disc diffusion assay against reference and clinical strains of A.baylyi and P. aeruginosa. Their MIC values were determined to quantify and compare their efficacies. Toxicity was determined using the Artemia franciscana nauplii bioassay. Active extracts were analysed by non-targeted HPLC-QTOF mass spectroscopy (with screening against 3 compound databases) and by GC-MS (with screening against 1 compound databases) for the identification and characterisation of individual components in crude plant extracts. Results: Methanolic, aqueous and ethyl acetate T. ferdinandiana leaf extracts displayed potent antibacterial activity in the disc diffusion assay against the bacterial triggers of multiple sclerosis (A.baylyi and P. aeruginosa). The methanol and ethyl acetate extracts had the most potent growth inhibitory activity, with MIC values less than 1000 μg/ ml against A. baylyi and P. aeruginosa (both reference and clinical strains). In comparison, the water extract was substantially less potent. Neither the chloroform nor hexane extracts inhibited the growth of any of the bacterial strains tested. All T. ferdinandiana fruit extracts were nontoxic in the Artemia fransiscana bioassay. Non-biased phytochemical analysis of the ethyl acetate extract revealed only low levels of the tannins gallic acid and chebulic acid and no other tannins. Conclusion: The low toxicity of the T. ferdinandiana fruit extracts and their potent inhibitory bioactivity against the bacterial triggers of multiple sclerosis indicates their potential as medicinal agents in the treatment and prevention of this disease. Phytochemical studies indicate that this activity is likely to be due to phytochemicals other than tannins.

Proton pump inhibitor alone vs proton pump inhibitor plus mucosal protective agents for endoscopic submucosal dissection-induced ulcer: A systematic review and meta-analysis

Article

Mar 2015
J CLIN BIOCHEM NUTR

Mucosal protective agents may improve healing of patients with endoscopic submucosal dissection-induced ulcers. The present study systematically evaluated published clinical trials to determine whether combined therapeutic use of mucosal protective agents and proton pump inhibitors can improve the outcome of patients with endoscopic submucosal dissection-induced ulcers compared to treatment with proton pump inhibitors alone. PubMed, the Cochrane Library, and the Igaku-Chuo-Zasshi database were searched to identify eligible randomized trials for systematic review. We identified 11 randomized trials for inclusion in our study (1,160 patients). Pooled endoscopic submucosal dissection-induced ulcer healing rates were 45.8% and 34.4% for patients with or without mucosal protective agents, respectively. The odds ratio was 2.28 (95% confidence interval, 1.57-3.31) with no significant study heterogeneity. In conclusion, the systematic review and meta-analysis showed that the combined therapeutic use of proton pump inhibitors and mucosal protective agents improved healing rates of endoscopic submucosal dissection-induced ulcers compared to treatment with proton pump inhibitor monotherapy.

Small bowel injury in low-dose aspirin users

Article

Full-text available

Dec 2014

The use of low-dose aspirin (LDA) is well known to be associated with an increased risk of serious upper gastrointestinal complications, such as peptic ulceration and bleeding. Until recently, attention was mainly focused on aspirin-induced damage of the stomach and duodenum. However, recently, there has been growing interest among gastroenterologists on the adverse effects of aspirin on the small bowel, especially as new endoscopic techniques, such as capsule endoscopy (CE) and balloon-assisted endoscopy, have become available for the evaluation of small bowel lesions. Preliminary CE studies conducted in healthy subjects have shown that short-term administration of LDA can induce mild mucosal inflammation of the small bowel. Furthermore, chronic use of LDA results in a variety of lesions in the small bowel, including multiple petechiae, loss of villi, erosions, and round, irregular, or punched-out ulcers. Some patients develop circumferential ulcers with stricture. In addition, to reduce the incidence of gastrointestinal lesions in LDA users, it is important for clinicians to confirm the differences in the gastrointestinal toxicity between different types of aspirin formulations in clinical use. Some studies suggest that enteric-coated aspirin may be more injurious to the small bowel mucosa than buffered aspirin. The ideal treatment for small bowel injury in patients taking LDA would be withdrawal of aspirin, however, LDA is used as an antiplatelet agent in the majority of patients, and its withdrawal could increase the risk of cardiovascular/cerebrovascular morbidity and mortality. Thus, novel means for the treatment of aspirin-induced enteropathy are urgently needed.

Protective Effects of Garlic Extract, PMK-S005, Against Nonsteroidal Anti-inflammatory Drugs-Induced Acute Gastric Damage in Rats

Article

Full-text available

Oct 2014
DIGEST DIS SCI

Background: PMK-S005 is synthetic s-allyl-L-cysteine (SAC), a sulfur-containing amino acid, which was initially isolated from garlic. The antioxidant and anti-inflammation activities of SAC have been demonstrated in diverse experimental animal models. Aims: The purpose of this study was to investigate the gastroprotective effects of PMK-S005 against NSAIDs-induced acute gastric damage in rats. Methods: Eight-week SD rats were pretreated with PMK-S005 (1, 5, or 10 mg/kg) or rebamipide (50 mg/kg) 1 h before administration of NSAIDs including aspirin (200 mg/kg), diclofenac (80 mg/kg), and indomethacin (40 mg/kg). After 4 h, the gross ulcer index, histological index, and gastric mucus level were determined. Myeloperoxidase (MPO), TNF-α, IL-1β, PGE2, and LTB4 levels were estimated in the gastric mucosal tissue by ELISA. Protein expressions of cPLA2, COX-1, and COX-2 were assessed by Western blot analysis. Results: Pretreatment with PMK-S005 significantly attenuated the NSAIDs-induced gastric damage and increased the gastric mucus level. In addition, PMK-S005 attenuated increases in MPO, TNF-α, and IL-1β production. The expressions of cPLA2 and COX-2 induced by NSAIDs were decreased by PMK-S005 pretreatment. PMK-S005 did not cause suppression of PGE2 synthesis induced by NSAIDs, but LTB4 production was significantly suppressed by PMK-S005. The effects of PMK-S005 were consistently maximized at a concentration of 5 mg/kg, which were frequently superior to those of rebamipide. Conclusions: These results strongly suggest that PMK-S005 can be a useful gastroprotective agent against acute gastric mucosal damage by suppressing proinflammatory cytokines, down-regulating cPLA2, COX-2 and LTB4 expression, and increasing the synthesis of mucus.

Rebamipide Plus Proton Pump Inhibitor Versus Proton Pump Inhibitor Alone in the Treatment of Endoscopic Submucosal Dissection-Induced Gastric Ulcer: A Meta-Analysis of Randomized Controlled Trials

Article

Full-text available

Sep 2014

Proton pump inhibitor (PPI) was the main prescription for gastric ulcer after endoscopic submucosal dissection (ESD). Some randomized controlled trials showed that a combination of rebamipide and PPI appears to be more efficient than PPI alone for the treatment of ESD-induced gastric ulcer. However, the sample sizes in these trials were limited and the conclusions were underpowered.This meta-analysis was conducted with 5 randomized controlled trials using the combination of rebamipide and PPI for healing ESD-induced ulcer compared with PPI monotherapy. Relevant studies were searched via MEDLINE, PubMed, Embase, and Cochrane Library databases by using terms such as "rebamipide," "proton pump inhibitor," "endoscopic submucosal dissection," "drug therapy," and "gastric ulcer or artificial ulcer."Five studies were included in this meta-analysis. The number of total patients was 626, with 317 patients in the combination group and 309 patients in the PPI alone group. The heterogeneity among these 5 studies was low (I = 22%, P = 0.28). All 5 studies considered scarring stage 1 rate as a primary endpoint, and the scarring stage 1 rate in combination group (115/317) was higher than that in PPI alone group (63/309) (odds ratio 2.61, 95% confidence interval [CI] 1.76-3.88). The mean difference of initial ulcer size between 2 groups was -4.46 (95% CI -266.61 to -257.69, P = 0.97), but it enlarged to 68.38 (95% CI 35.72-101.05, P < 0.00001) in the 4th week.This meta-analysis demonstrates that combination therapy is more efficient than PPI monotherapy in healing ESD-induced gastric ulcer.

Comparative study of esomeprazole and lansoprazole in triple therapy for eradication of Helicobacter pylori in Japan

Article

Full-text available

Apr 2014
WORLD J GASTROENTERO

To evaluate the efficacy and safety of esomeprazole-based triple therapy compared with lansoprazole therapy as first-line eradication therapy for patients with Helicobacter pylori (H. pylori) in usual post-marketing use in Japan, where the clarithromycin (CAM) resistance rate is 30%. For this multicenter, randomized, open-label, non-inferiority trial, we recruited patients (≥ 20 years of age) with H. pylori infection from 20 hospitals in Japan. We randomly allocated patients to esomeprazole therapy (esomeprazole 20 mg, CAM 400 mg, amoxicillin (AC) 750 mg for the first 7 d, with all drugs given twice daily) or lansoprazole therapy (lansoprazole 30 mg, CAM 400 mg, AC 750 mg for the first 7 d, with all drugs given twice daily) using a minimization method with age, sex, and institution as adjustment factors. Our primary outcome was the eradication rate by intention-to-treat (ITT) and per-protocol (PP) analyses. H. pylori eradication was confirmed by a urea breath test from 4 to 8 wk after cessation of therapy. ITT analysis revealed the eradication rates of 69.4% (95%CI: 61.2%-76.6%) for esomeprazole therapy and 73.9% (95%CI: 65.9%-80.6%) for lansoprazole therapy (P = 0.4982). PP analysis showed eradication rate of 76.9% (95%CI: 68.6%-83.5%) for esomeprazole therapy and 79.8% (95%CI: 71.9%-86.0%) for lansoprazole therapy (P = 0.6423). There were no differences in adverse effects between the two therapies. Esomeprazole showed non-inferiority and safety in a 7 day-triple therapy for eradication of H. pylori compared with lansoprazole.

Efficacy of treatment with rebamipide for endoscopic submucosal dissection-induced ulcers

Article

Full-text available

Sep 2013
WORLD J GASTROENTERO

To prospectively compare the healing rates of endoscopic submucosal dissection (ESD)-induced ulcers treated with either a proton-pump inhibitor (PPI) or rebamipide. We examined 90 patients with early gastric cancer who had undergone ESD. All patients were administered an intravenous infusion of the PPI lansoprazole (20 mg) every 12 h for 2 d, followed by oral administration of lansoprazole (30 mg/d, 5 d). After 7-d treatment, the patients were randomly assigned to 2 groups and received either lansoprazole (30 mg/d orally, n = 45; PPI group) or rebamipide (300 mg orally, three times a day; n = 45; rebamipide group). At 4 and 8 wk after ESD, the ulcer outcomes in the 2 groups were compared. No significant differences were noted in patient age, underlying disease, tumor location, Helicobacter pylori infection rate, or ESD-induced ulcer size between the 2 groups. At both 4 and 8 wk, the healing rates of ESD-induced ulcers were similar in the PPI-treated and the rebamipide-treated patients (4 wk: PPI, 27.2%; rebamipide, 33.3%; P = 0.5341; 8 wk: PPI, 90.9%; rebamipide, 93.3%; P = 0.6710). At 8 wk, the rates of granulation lesions following ulcer healing were significantly higher in the PPI-treated group (13.6%) than in the rebamipide-treated group (0.0%; P = 0.0103). Ulcer-related symptoms were similar in the 2 treatment groups at 8 wk. The medication cost of 8-wk treatment with the PPI was 10945 yen vs 4889 yen for rebamipide. No ulcer bleeding or complications due to the drugs were observed in either treatment group. The healing rate of ESD-induced ulcers was similar with rebamipide or PPI treatment; however, rebamipide treatment is more cost-effective and prevents granulation lesions following ulcer healing.

Gastric healing effect of methanolic and alkaloidic fraction from Strychnos pseudoquina

Article

Full-text available

Jul 2009

Combination of proton pump inhibitor and rebamipide, a free radical scavenger, promotes artificial ulcer healing after endoscopic submucosal dissection with dissection size >40 mm

Article

Full-text available

Nov 2012
J CLIN BIOCHEM NUTR

In our previous study, the healing effect of proton pump inhibitor plus rebamipide for endoscopic submucosal dissection-related artificial ulcer smaller than 40 mm showed statistical significance. However, such effect of the combination was not yet clear for ulcers with dissected diameter more than 40 mm. The aim of this present study was to resolve this problem under sufficient statistical power, with adequate sample size. We conducted a randomized controlled study. Either the proton pump inhibitor mono-therapy or the combination therapy was prescribed for 28 days after endoscopic submucosal dissection. Eighty-seven patients were eligible for outcome evaluation. Combination therapy was significantly superior to mono-therapy, 27.8% vs 0% reached healing stage (scar stage) in cases with ulcers of dissection diameter more than 40 mm. In conclusion, the combination therapy with rebamipide was favorable regimen in patients with larger artificial ulcer after endoscopic submucosal dissection.

Diagnostics and Treatment of Peptic Ulcer in Adults (Clinical Guidelines of the Russian Gastroenterological Association, the Russian Society of Colorectal Surgeons, the Russian Endoscopic Society and the Scientific Society for the Clinical Study of Human Microbiome)

Article

Full-text available

May 2024

Aim . The guidelines set out the modern methods of diagnostics and treatment of peptic ulcer and are created for gastroenterologists, primary care physicians, general practitioners, surgeons, endoscopists. Key points . The clinical guidelines contain modern views on the etiology and pathogenesis of peptic ulcer, its clinical features, methods of laboratory and instrumental diagnostics, the main approaches to conservative and surgical treatment. They include the criteria for assessment of the quality of medical care, the algorithm of the doctor's actions, as well as information for the patient. Conclusion . Knowledge of modern methods of diagnostics and therapy of peptic ulcers will contribute to improving the results of its treatment.

Rebamipide and Derivatives are Potent, Selective Inhibitors of Histidine Phosphatase Activity of the Suppressor of T Cell Receptor Signaling Proteins

Article

Jan 2024
J MED CHEM

Gastroprotectant Rebamipide: review of action mechanisms and clinical applications

Article

Mar 2022

Rebamipide has a long history of use as a gastroprotective drug. However, a large amount of recent experimental data has made it possible to identify the multiple effects of rebamipide and expand the scope of its application. The purpose of this publication is to review and systematize knowledge about the mechanisms of action of rebamipide and discuss the field of its clinical application, which has an evidence base.

Rebamipide using in gastroesophageal reflux disease treatment

Article

Full-text available

May 2020

Rebamipide is a mucoprotective drug which was developed in Japan in 1990. The therapeutic effect of rebamipide based on the induction of cyclooxygenase-2 and increasing level of prostaglandins, inhibition of oxygen free radicals production, epidermal growth factor stimulation, vascular endothelial growth factor, nitric oxide, and decreasing of lipid peroxidation and neutrophils migration. The combination of proton pump inhibitors and rebamipide is more effective in relieving of gastroesophageal reflux disease symptoms and reducing recurrence rate of disease. Using rebamipide in the treatment of gastroesophageal reflux disease is justified because this drug has a unique mechanism of action, which eliminating the main stages of pathogenesis of the disease.

The Mexican consensus on the diagnosis, treatment, and prevention of NSAID-induced gastropathy and enteropathy

Article

Full-text available

Mar 2020

Comparison of efficacy of pharmacological therapies for gastric endoscopic submucosal dissection-induced ulcers: a systematic review and network meta-analysis

Article

Feb 2020

Objectives: The efficacy of various anti-ulcer medications in the healing of post-gastric endoscopic submucosal dissection (ESD)-induced ulcers has not been fully evaluated. This study aimed to compare the efficacy of various anti-ulcer medications in preventing delayed bleeding and promoting ulcer healing after ESD. Methods: A systematic search was conducted for articles up to August 2019. The treatments of iatrogenic ulcer were analyzed by Bayesian network meta-analysis. Results: The analysis included 28 studies. Six treatments were compared. For prevention of delayed bleeding, potassium-competitive acid blocker (P-CAB) alone was superior to proton-pump inhibitor (PPI) alone [RR=1.02, 95%CI (1.00, 1.05)]. Treatments based on P-CAB tended to be better than the non-P-CAB groups [RR=1.05, 95%CI (1.03, 1.07)]. Concerning the ulcer healing rate at 4 weeks after ESD, the combined treatment of PPI and mucoprotective agent (MP) was superior to PPI alone [RR=1.81, 95%CI (1.19, 2.76)] and P-CAB alone [RR=2.75, 95%CI (1.02, 7.44)]. At 8 weeks, PPI+MP was superior to MP alone [RR=1.19, 95%CI (1.00, 1.40)], histamine-2 receptor antagonist (H2RA) alone [RR=1.20, 95%CI (1.03, 1.40)], P-CAB alone [RR=1.20, 95%CI (1.02, 1.41)], and PPI alone [RR=1.23, 95%CI (1.10, 1.37)]. P-CAB+MP was superior to PPI alone [RR=1.23, 95%CI (1.04, 1.46)]. The healing effect of MP-based therapies was better than that of non-MP groups [RR=1.63, 95%CI (1.32, 2.01)] at 4 weeks and better than that of non-MP groups at 8 weeks [RR=1.06, 95%CI (1.02, 1.11)]. Conclusion: P-CAB may prevent delayed bleeding, but not significantly. MP agents have potential to heal post-ESD ulcers. The results of this study will help in the selection of treatment options for patients with iatrogenic ulcers.

Rebamipide suppresses 5-fluorouracil-induced cell death via the activation of Akt/mTOR pathway and regulates the expression of Bcl-2 family proteins

Article

Oct 2017
TOXICOL IN VITRO

Oral mucositis is a common adverse effect of chemotherapy that limits the required dose of chemotherapeutic agents. Numerous attempts to mitigate chemotherapy-induced oral mucositis have failed to identify an appropriate treatment. Recently, it has been indicated that rebamipide prevents chemoradiotherapy-induced oral mucositis in patients. However, the details of the underlying mechanism involved in the cytoprotective effect of rebamipide remain obscure. In the present study, we investigated the mechanism behind rebamipide cytoprotective effect in the oral mucosa using primary normal human oral keratinocytes (NHOK cells). We found that rebamipide prevented 5-fluorouracil (5-FU)-induced cell death in NHOK cells. In addition, rebamipide increased the levels of phosphorylated Akt and mTOR, enhanced the Bcl-2 and Bcl-xL expressions, and suppressed the expression of Bax and Bim. This is in contrast to 5-FU-induced suppression of Akt and mTOR activation, Bcl-2 and Bcl-xL expressions, and the enhanced expression of Bax and Bim. These findings suggest that rebamipide can potentially be used for the protection of oral mucosa from chemotherapy-induced mucositis. This is the first study that elucidates the specific molecular pathway for the cytoprotective effect of rebamipide.

Prostaglandins and other mucosal protecting agents

Chapter

Jan 2014

Prostaglandins are derived from arachidonic acid, which originates from cell membrane phospholipids by the action of phospholipase A2. These compounds were found to be crucial for the maintenance of gastroduodenal mucosal integrity, so-called “cytoprotection,” and Vane suggested that the inhibition of prostaglandin biosynthesis by NSAIDs may underlie the ability of this class of drugs to induce ulceration in the gastrointestinal tract. Misoprostol is a synthetic prostaglandin E1 (PGE1) analog, which despite its beneficial cytoprotective properties, is clinically effective only at doses high enough to reduce gastric acid secretion. It is used principally in the prevention of NSAID-related gastroduodenal ulcer and its complications. Sucralfate, a basic aluminum salt of sucrose octasulfate, is effective in the treatment and prophylaxis of non-NSAID duodenal ulcers and appears to be as effective as H2-antagonists in the healing of non-NSAID gastric ulcers. However, this agent has no proven benefit in the treatment of NSAID-related gastric ulcers. Rebamipide was developed in Japan as a gastroprotective drug and is used in the treatment of gastroduodenal ulcers. Its precise mechanisms of action have not been clearly elucidated.

Protective effect and mechanism of rebamipide on human gastric mucosal epithelial cell injury induced by clopidogrel

Article

Jan 2015

Background: Long-term use of clopidogrel may cause gastrointestinal injury. Rebamipide is a novel mucoprotective drug, however, its protective effect on gastric mucosal injury induced by clopidogrel has not been clarified. Aims: To investigate the protective effect and potential mechanism of rebamipide on human gastric mucosal epithelial cell injury induced by clopidogrel. Methods: In clopidogrel group, human gastric mucosal epithelial cell line GES-1 was treated with clopidogrel; GES-1 cells in rebamipide group were pretreated with different concentrations of rebamipide (0.2, 0.5 and 1.0 mmol/L) before clopidogrel treatment, and a negative control group was established simultaneously. Inhibition of cell proliferation was measured by MTT assay. Morphological change of cell was observed by inverted phase contrast microscope. Expressions of trefoil factor family 1 (TFF1) and phosphorylated extracellular signal regulated kinase 1/2 (p-ERK1/2) were determined by Western blotting. Results: MTT assay showed that cell proliferation inhibition rates of GES-1 cells in rebamipide 0.2, 0.5 and 1.0 mmol/L groups were significantly lower than that in clopidogrel group (P<0.05). Injury of GES-1 cells was seen in clopidogrel group by inverted phase contrast microscope and rebamipide could reduce the cell injury. Expression of TFF1 in GES-1 cells in clopidogrel group was significantly higher than that in negative control group (P<0.05), while those in rebamipide 0.2, 0.5 and 1.0 mmol/L groups were further increased in a dose-dependent manner as compared with that in clopidogrel group (P<0.05). Expression of p-ERK1/2 in GES-1 cells in clopidogrel group was significantly higher than that in negative control group (P<0.05), while those in rebamipide 0.2, 0.5 and 1.0 mmol/L groups were significantly lower than that in clopidogrel group in a dose-dependent manner (P<0.05). Conclusions: Rebamipide has a protective effect on GES-1 cells injury induced by clopidogrel, probably through inhibiting ERK signaling pathway, up-regulating TFF1 expression and promoting mucosal healing. COPYRIGHT © 2015 by the Editorial Office of Chinese Journal of Gastroenterology.

Epidemiology of Low Dose Aspirin Damage in the Lower Gastrointestinal Tract

Article

Sep 2015
CURR PHARM DESIGN

Low dose aspirin (ASA), commonly defined as the cardiovascular (CV) dose of 75 to 325 mg daily, is one of the most widely prescribed drugs in the world and the cornerstone of therapy and prophylaxis for CV disease. However, the use of low dose ASA is well known to be associated with an increased risk of different upper and lower gastrointestinal (GI) complications, such as peptic ulceration and bleeding. In the recent past, clinical research was mainly focused on ASA-related injury of the upper GI tract. However, the introduction of new endoscopic techniques, such as capsule endoscopy and balloon-assisted endoscopy for the evaluation of small bowel lesions have resulted in an increasing interest among gastroenterologists about the side effects of ASA on the large and small bowel. Furthermore, it has been demonstrated that chronic use of low dose ASA results in a variety of lesions in the lower GI tract, including multiple petechiae, erosions, ulcers, diverticular bleeding and even circumferential ulcers with stricture. The ideal treatment for small bowel injury in low dose ASA users would be withdrawal of ASA, however, this withdrawal could increase the risk of CV/cerebrovascular morbidity and mortality in high percentage of patients. Therefore, several drugs have been evaluated to identify the best choice to prevent or treat ASA-induced small bowel injury with different results. Nevertheless, further specifically designed studies with more sample size are needed to determine the best treatment for low dose ASA related GI injury.

Efficacy of proton pump inhibitors plus rebamipide for endoscopic submucosal dissection-induced ulcers: A Meta-analysis of randomized controlled trials

Article

Jan 2015

Ye-Zhou Ding

The effect of short-term proton pump inhibitor plus anti-ulcer drug on the healing of endoscopic submucosal dissection-derived artificial ulcer: A randomized controlled trial

Article

Apr 2015
HEPATO-GASTROENTEROL

Artificial ulcers remain a major complication after Endoscopic submucosal dissection (ESD). The development of more effective treatment regimen for this ulcer is required than the use of proton pump inhibitor (PPI) alone. Patients with ESD-derived artificial ulcers were randomly assigned to two groups: a group of patients who received rabeprazole 20 mg daily for 8 weeks (PPI group) and a group of patients who received a combination of rebamipide 300 mg daily for 8 weeks and rabeprazole 20 mg dairy for the first 4 weeks (reb+PPI group). The area reduction ratio and healing status of ulcers were evaluated endoscopically on postoperative 7, 28 and 56 days. The overall ulcer area reduction ratio was higher in the reb+PPI group than in the PPI group, especially at an early stage. The ratio of progression to the H1 stage in the reb+PPI group was significantly higher than that in the PPI group, especially at an early stage. Treatment with 8 weeks of rebamipide plus the first 4 weeks of PPI demonstrated a reduction ratio of artificial ulcers superior to that with 8 weeks of PPI mono-therapy. This combination treatment is, therefore, one of the candidate treatment strategies against ESD-derived artificial ulcers.

Effect of supplementation with rebamipide for Helicobacter pylori eradication therapy: A systematic review and meta-analysis

Article

Dec 2014

Several studies have reported that the application of rebamipide during the eradication of Helicobacter pylori can improve the eradication rate. However, the efficacy and safety are controversial. The present study systematically evaluated whether rebamipide improves the eradication rate of H. pylori by conducting a meta-analysis based on randomized controlled trials (RCTs). Literature searches were conducted in the following database: PubMed, the Cochrane Library, and the Igaku-chuo-zasshi database in Japan. A meta-analysis of all RCTs comparing rebamipide supplementation with non-rebamipide-containing therapy was performed. We identified six randomized trials (611 patients). Pooled H. pylori eradication rates by per-protocol analysis were 73.3% and 61.4% for patients with or without rebamipide, respectively. The odds ratio was 1.74 (95% confidence interval. 1.19-2.53). Supplementation with rebamipide might be effective in increasing the H. pylori eradication rates of proton-pump inhibitor-amoxicillin dual therapy. © 2014 Journal of Gastroenterology and Hepatology Foundation and Wiley Publishing Asia Pty Ltd.

Efficacy and Safety of Proton Pump Inhibitors (PPIs) Plus Rebamipide for Endoscopic Submucosal Dissection-induced Ulcers: A Meta-analysis

Article

Jun 2014

Objective: To compare the efficacy of proton pump inhibitors (PPIs) with rebamipide versus PPIs alone for the treatment of ulcers after endoscopic submucosal dissection (ESD). Methods: PubMed, Web of Science, Medline, Embase, the Cochrane Central Register of Controlled Trials and China Naitonal Knowledge Infrastructure were searched up to the end of October 2013 in order to identify all randomized controlled trials reporting the effects of PPIs plus rebamipide on healing ulcers after ESD. The outcome measurement was complete ulcer healing. Results: A total of six studies involving 724 patients were included. The pooled data suggested a significantly higher rate of ulcer healing after endoscopic therapy among patients treated with PPIs plus rebamipide than among those treated with PPIs alone [odds ratio (OR)=2.40, 95% confidence interval (CI): 1.68-3.44]. The subgroup analysis showed PPI plus rebamipide therapy to be more effective in healing ESD-induced ulcers than treatment with PPIs alone after both four (OR=2.22, 95%CI: 1.53-3.24) and eight weeks of treatment (OR=3.19, 95%CI: 1.22-8.31). In addition, the combination therapy was found to be significantly more effective than the use of PPIs alone for all ESD ulcers greater than 20 mm in size (OR=4.77, 95%CI: 2.22-10.26). There were no significant differences between the treatment groups with regard to ulcer location (low, middle or upper stomach) or the presence of absence of H. pylori infection. No serious adverse events were observed in either group. Conclusion: The results of this meta-analysis suggest that treatment with PPIs plus rebamipide is superior to PPI monotherapy for healing ESD-induced ulcers over four weeks, particularly large ulcers. However, more well-designed trials are needed to confirm these findings.

Strategies for peptic ulcer healing after 1 week proton pump inhibitor-based triple Helicobacter pylori eradication therapy in Japanese patients: Differences of gastric ulcers and duodenal ulcers

Article

Full-text available

Nov 2012
J CLIN BIOCHEM NUTR

Helicobacter pylori (H. pylori) eradication therapy alone is insufficient to ensure healing of large ulcers with H. pylori-positive gastric ulcer (GU). The question of what is the optimum antiulcer treatment following H. pylori eradication therapy has not been fully elucidated. Furthermore, the ulcer healing effects of eradication therapy itself with H. pylori-positive duodenal ulcer (DU) have not been investigated. In GU study, the eradication therapy + proton pump inhibitor (PPI) group (group A) were administered eradication therapy followed by 7 weeks of a PPI, and the eradication therapy + gastroprotective drug (GP) group (group B) eradication therapy followed by 7 weeks of a GP. In DU study, the eradication therapy + PPI group (group C) were administered eradication therapy followed by 5 weeks of a PPI, and the eradication therapy only group (group D) was eradication therapy alone. In GU study, healing rates for ulcer of ≥15 mm in diameter were significant greater in the group A. In DU study, high healing rates were seen both the group C and D. In conclusion, a PPI could significantly heal GU than a GP after eradication therapy in GU. Meanwhile, the eradication alone is sufficient for DU.

Rebamipide Activates Genes Encoding Angiogenic Growth Factors and Cox2 and Stimulates Angiogenesis: A Key to Its Ulcer Healing Action?

Article

Full-text available

Mar 2004

Clinical and experimental data indicate that rebamipide accelerates ulcer healing, improves scar quality, and prevents ulcer recurrence. However, the mechanisms responsible for these rebamipides' actions are not fully elucidated. We studied, using gene expression microarray analysis, which of the ulcer healing genes are activated by rebamipide treatment. Normal rat gastric epithelial cells (RGM1) were treated with either vehicle or rebamipide. Gene expression was determined using Affymetrix rat genome U34A gene chip arrays and data were analyzed using the GeneSpring program. Activation of some of the genes and protein translation were also examined by RT/PCR and Western blotting. Rebamipide significantly upregulated the proangiogenic genes encoding vascular endothelial growth factor (VEGF), by 7.5-fold, heparin binding epidermal growth-like factor (HB-EGF), by approximately 5-fold, fibroblast growth factor receptor-2 (FGFR2), by 4.4-fold, and cyclooxygenase-2 (Cox2), by 9.3-fold, as well as growth promoting genes, e.g., insulin growth factor-1 (IGF-1), by 5-fold. RT/PCR and Western blotting demonstrated that Cox2 mRNA and protein were upregulated; the latter, approximately 6-fold. Treatment of rat gastric mucosal endothelial cells with rebamipide stimulated in vitro angiogenesis by approximately 240% (vs. controls, P < 0.001). Conclusions are as follows. (1) Rebamipide activates in gastric epithelial RGM-1 cells a genetic program that promotes angiogenesis and signals cell growth and tissue regeneration. (2) In addition, rebamipide treatment directly stimulates angiogenesis in gastric microvascular endothelial cells. Thus rebamipide has two separate and distinct mechanisms of proangiogenic action: one through activation in gastric epithelial cells of proangiogenic growth factor genes and the second a direct angiogenic action on microvascular endothelial cells.

Current concepts in the management of Helicobacter pylori infection-The Maastricht 2-2000 Consensus Report

Article

Feb 2002

Significant progress and new insights have been gained in the 4 years since the first Maastricht Consensus Report, necessitating an update of the original guidelines. To achieve this, the European Helicobacter Pylori Study Group organized a meeting of specialists and experts from around the world, representatives from National Gastroenterology Societies and general practitioners from Europe to establish updated guidelines on the current management of Helicobacter pylori infection. The meeting took place on 21–22 September 2000. A ‘test and treat’ approach is recommended in adult patients under the age of 45 years (the age cut‐off may vary locally) presenting in primary care with persistent dyspepsia, having excluded those with predominantly gastro‐oesophageal reflux disease symptoms, non‐steroidal anti‐inflammatory drug users and those with alarm symptoms. Diagnosis of infection should be by urea breath test or stool antigen test. As in the previous guidelines, the eradication of H. pylori is strongly recommended in all patients with peptic ulcer, including those with complications, in those with low‐grade gastric mucosa‐associated lymphoid tissue lymphoma, in those with atrophic gastritis and following gastric cancer resection. It is also strongly recommended in patients who are first‐degree relatives of gastric cancer patients and according to patients’ wishes after full consultation. It is advised that H. pylori eradication is considered to be an appropriate option in infected patients with functional dyspepsia, as it leads to long‐term symptom improvement in a subset of patients. There was consensus that the eradication of H. pylori is not associated with the development of gastro‐oesophageal reflux disease in most cases, and does not exacerbate existing gastro‐oesophageal reflux disease. It was agreed that the eradication of H. pylori prior to the use of non‐steroidal anti‐inflammatory drugs reduces the incidence of peptic ulcer, but does not enhance the healing of gastric or duodenal ulcer in patients receiving antisecretory therapy who continue to take non‐steroidal anti‐inflammatory drugs. Treatment should be thought of as a package which considers first‐ and second‐line eradication therapies together. First‐line therapy should be with triple therapy using a proton pump inhibitor or ranitidine bismuth citrate, combined with clarithromycin and amoxicillin or metronidazole. Second‐line therapy should use quadruple therapy with a proton pump inhibitor, bismuth, metronidazole and tetracycline. Where bismuth is not available, second‐line therapy should be with proton pump inhibitor‐based triple therapy. If second‐line quadruple therapy fails in primary care, patients should be referred to a specialist. Subsequent failures should be handled on a case‐by‐case basis by the specialist. In patients with uncomplicated duodenal ulcer, eradication therapy does not need to be followed by further antisecretory treatment. Successful eradica‐ tion should always be confirmed by urea breath test or an endoscopy‐based test if endoscopy is clinically indicated. Stool antigen test is the alternative if urea breath test is not available.

Gastric mucosal protection by OPC-12759, a novel antiulcer compound, in the rat

Article

Nov 1987
EUR J PHARMACOL

OPC-12759, 2-(4-chlorobenzoylamino)-3-[2(1H)-quinolinon-4-yl]-propionic acid, was studied for its efficacy to prevent the gastric mucosal damage induced by several necrotizing agents. Experiments were also performed to elucidate the mechanism of this mucosal protective activity. OPC-12759 dose dependently prevented the formation of mucosal necrosis induced by absolute ethanol, 0.2 N NaOH or 0.6 N HCl. PGE2 was also shown to prevent the gastric mucosal erosion induced by necrotizing agents. The mucosal protective effect of OPC-12759 was completely counteracted by pretreatment with indomethacin while that of PGE2 was not. In addition, OPC-12759 given alone increased the generation of gastric mucosal PGE2-like activity. OPC-12759 dose dependently reduced the volume, acid output and pepsin output of the gastric juice in pylorus-ligated rats. The inhibitory effect of OPC-12759 but not of cimetidine or atropine on gastric secretion was also abolished by concurrent administration of indomethacin. These findings suggest that the mucosal protective effect and antisecretory effect of OPC-12759 presumably result from enhancement of the generation of endogenous PGs.

Prevention of ulcer recurrence after eradication of Helicobacter pylori: A prospective long-term follow-up study

Article

Oct 1997
GASTROENTEROLOGY

Short-term follow-up studies show lower relapse rates of duodenal and gastric ulcers after successful Helicobacter pylori eradication. The aim of this study was to determine the long-term outcome of ulcer disease after successful H. pylori eradication. We prospectively studied the long-term effect of H. pylori eradication on ulcer recurrence rates in patients after endoscopically proven healing of duodenal or gastric ulcers between 1984 and 1995. Patients using nonsteroidal anti-inflammatory drugs (NSAIDs), aspirin, or maintenance antisecretory therapy were excluded. H. pylori infection was assessed by culture and histopathology of gastric biopsy specimens. After endoscopically proven ulcer healing and successful H. pylori eradication, 186 patients with ulcers underwent elective endoscopy every 3 months during the first year of follow-up and were advised to contact us at symptom recurrence. Thereafter, 96 patients were available for elective half-yearly endoscopies. The 89 patients who did not choose to undergo the repeated endoscopies were asked about symptom recurrence and to undergo elective endoscopy in 1995. Successful H. pylori eradication was achieved in 141 patients with duodenal ulcers and 45 patients with gastric ulcers. None of the 141 H. pylori-eradicated patients with duodenal ulcers had an ulcer relapse after follow-up of 367 patient-years. Ulcer relapses were also absent in the 45 H. pylori-eradicated patients with gastric ulcers after 113 patient-years of follow-up. Excluding patients taking aspirin or NSAIDs, recurrence of duodenal or gastric ulcers is completely prevented after successful H. pylori eradication for up to 9.8 years.

Rebamipide prevents recurrence of gastric ulcers without affecting Helicobacter pylori status

Article

Oct 1998

Rebamipide, a gastroprotective drug developed in Japan, accelerates ulcer healing and reduces recurrence of experimental gastric ulcers. We examined the effects of rebamipide, given during healing of human gastric ulcers infected with Helicobacter pylori, on the quality of ulcer healing and ulcer recurrence. Sixty H. pylori-positive patients with gastric ulcers were randomly allocated to three treatment groups: group O (N = 20) received 20 mg of omeprazole every day for eight weeks, group OR (N = 20) received the same dose of omeprazole and 300 mg of rebamipide three times a day for eight weeks, and group OA (N = 20) received the same dose of omeprazole for eight weeks and 1500 mg of amoxicillin three times a day for the first two weeks. After this treatment was completed no other medication was given. Endoscopic examinations were performed at the end of therapy (for healing rate), one month later (for rate of H. pylori eradication) and every three months for follow-up (for ulcer recurrence rate). At the end of therapy, biopsy specimens were taken from the gastric ulcer scar and examined under the microscope for neutrophil and mononuclear cell infiltration. The ulcer healing rate of the three groups was almost the same; H. pylori in group OA was 65% and that of the other two groups was 0%. The number of patients with a flat ulcer scar pattern (good quality of ulcer healing) was increased and the neutrophil infiltration was significantly improved in groups OR and OA compared to group O. The ulcer recurrence rate was significantly lower in group OA and group OR than in group O. In conclusion, rebamipide is almost equipotent to amoxicillin plus omeprazole for the reduction of ulcer recurrence. The decreased recurrence rate by rebamipide may be due to improvement of the quality of ulcer healing, reflected as in the suppression of inflammatory cell infiltration in the scar, which results from either cure of H. pylori infection and/or treatment with a gastroprotective drug such as rebamipide.

Guidelines in the Management of Helicobacter pylori Infection in Japan

Article

Oct 2001

In preparation of the approval of Helicobacter pylori therapy by the Japanese national health system, the board of directors of the Japanese Society for Helicobacter Research decided to prepare guidelines on the diagnosis and treatment of H. pylori infection for physicians in routine medical practice. A guidelines preparation committee was formed and six meetings were held. Then, in December 1999, a consensus meeting was held in Kobe to obtain the opinions of general practitioners as well as experts from Europe, North America, and Asia. Helicobacter pylori eradication therapy is recommended in gastric or duodenal ulcer patients. Helicobacter pylori eradication therapy is recommended or gastric mucosa associated lymphoid tissue (MALT) lymphoma but it should be done at specialist institutions. The significance of H. pylori eradication therapy is still under evaluation in patients with hyperplastic polyps, chronic atrophic gastritis, non-ulcer dyspepsia and in patients after endoscopic mucosal resection of gastric cancer and after gastrectomy for gastric cancer. When diagnosing H. pylori infection, at least one of the tests requiring endoscopic biopsy (e.g. rapid urease test, histology, or culture) and tests not requiring biopsy (e.g. measurement of H. pylori antibody or urea breath test) should be used. Multiple tests are recommended to increase the accuracy. The drugs of first choice currently covered by the national health insurance system in Japan are: lansoprazole (30 mg) 1 capsule twice daily, amoxicillin (250 mg) 3 capsules twice daily, and clarithromycin (200 mg) 1-2 tablets twice daily. These three drugs should be administered after breakfast and dinner for 1 week. These guidelines are intended for utilization in routine medical practice after the Japanese national health system begins to cover the management of H. pylori infection.

Drug combinations with amoxycillin reduce selection of clarithromycin resistance during Helicobacter pylori eradication therapy

Article

Feb 2002
INT J ANTIMICROB AG

This study investigated the relationship between the drug combinations of the eradication regimens and the prevalence of acquired resistance to clarithromycin. Of 540 patients treated with anti-Helicobacter pylori regimens containing clarithromycin, 55 patients (31 males, mean age, 45.6 years) with failed eradication of H. pylori that was susceptible to clarithromycin before treatment were included. The E test was used to test for susceptibility to clarithromycin (minimum inhibitory concentration (MIC) <1 mg/l). Of the 55 patients, 33 (60.0%) developed clarithromycin resistance after failed eradication. Of the dual therapies, the combination of a proton pump inhibitor (PPI) and clarithromycin resulted in 88.9% (8/9) of the patients acquiring clarithromycic-resistance. With the triple therapies, the percentages of patients acquiring clarithromycin resistant strains after using a PPI+clarithromycin+amoxycillin or a PPI+clarithromycin+metronidazole were 38.7% (12/31) and 90.0% (9/10), respectively (P<0.01). These data suggest that regimens containing amoxycillin may prevent the selection of secondary clarithromycin resistance.

Is eradication sufficient to heal gastric ulcers in patients infected with Helicobacter pylori? A randomized, controlled, prospective study

Article

Feb 2003

In Helicobacter pylori infection, the effect of short-term triple therapy with proton pump inhibitor plus two antibiotics on gastric ulcer healing is not well known. To compare 1-week triple therapy with 8-week proton pump inhibitor therapy on gastric ulcer healing in infected patients. We randomly assigned 120 patients with H. pylori and gastric ulcers to proton pump inhibitor plus amoxicillin and clarithromycin for 1 week (n = 61) or proton pump inhibitor alone for 8 weeks (n = 59), with endoscopic assessment of ulcer healing 8 weeks after the start of treatment. Triple therapy eradicated H. pylori in 51 patients [intention-to-treat, 84%; 95% confidence interval (CI), 75-93%]. At 8 weeks, gastric ulcers were healed in 30 patients given triple therapy (49%; 95% CI, 37-62%) and in 49 patients given proton pump inhibitor (83%; 95% CI, 73-93%, P < 0.001). Healing rates in the triple therapy and proton pump inhibitor-only groups were 89% and 100%, respectively, for ulcers of < 1.0 cm in diameter, 54% and 77% for ulcers of 1.0 to < 1.5 cm in diameter, and 5% and 77% (P < 0.001) for ulcers of > or = 1.5 cm in diameter. One-week triple therapy healed most ulcers of < 1.0 cm, but not ulcers of > or = 1.5 cm. Short-term therapy is effective for gastric ulcers of < 1.0 cm, but, for larger ulcers, follow-up therapy to suppress acid is needed.

Influence of anti-ulcer drugs used in Japan on the result of C-13-urea breath test for the diagnosis of Helicobacter pylori infection

Article

Feb 2003

The (13)C-urea breath test (UBT) is a simple breath test for the diagnosis of Helicobacter pylori infection, but several factors have been reported to affect the results of this test. In this study, the effects of the antiulcer drugs used in Japan on the results of UBT were determined. The subjects of the study were 64 adult volunteers who tested positive for H. pylori infection by the serum antibody method. Eight classes of anti-ulcer drugs used in Japan were administered at their usual doses to these subjects: lansoprazole, a proton pump inhibitor (PPI); nizatidine, an H(2)-receptor antagonist (H(2)RA); and polaprezinc, ecabet sodium, rebamipide, teprenone, cetraxate hydrochloride, and sucralfate, all mucoprotective agents. The study drugs were randomized for administration to the subjects, and each of the drugs was administered for 14 consecutive days. The UBT was performed on days 0, 14, and 21. The mean Delta(13)C per thousand in the lansoprazole group was significantly decreased on day 14, to below 10 per thousand, in 4 of 16 subjects, and in 1 of the 4 subjects, the test result was negative, with the Delta(13)C per thousand falling to 1.7 per thousand. The value returned to baseline 1 week after the discontinuation of lansoprazole. The other drugs administered had no significant effect on the result of the UBT, except that the mean Delta(13)C per thousand showed a tendency to decrease after the administration of ecabet sodium and rebamipide. Administration of a PPI may produce a false-negative UBT result, while other anti-ulcer drugs, for the most part, have little effect on the result of the UBT when used alone. The (13)C-urea breath test (UBT) is a simple test for the diagnosis of Helicobacter pylori infection, but several factors have been reported to affect the results of this test. In this study, the effects of the anti-ulcer drugs used in Japan on the results of the UBT were determined.

Recurrent Peptic Ulcers in Patients Following Successful Helicobacter pylori Eradication: A Multicenter Study of 4940 Patients

Article

Mar 2004

Although curative treatment of Helicobacter pylori infection markedly reduces the relapse of peptic ulcers, the details of the ulcers that do recur is not well characterized. The aim of this study is to describe the recurrence rate and specific features of peptic ulcers after cure of H. pylori infection. This was a multicenter study involving 4940 peptic ulcer patients who were H. pylori negative after successful eradication treatment and were followed for up to 48 months. The annual incidence of ulcer relapse in H. pylori-cured patients, background of patients with relapsed ulcers, time to relapse, ulcer size, and site of relapsed ulcers were investigated. Crude peptic ulcer recurrence rate was 3.02% (149/4940). The annual recurrence rates of gastric, duodenal and gastroduodenal ulcer were 2.3%, 1.6%, and 1.6%, respectively. Exclusion of patients who took NSAIDs led annual recurrence rates to 1.9%, 1.5% and 1.3%, respectively. The recurrence rate was significantly higher in gastric ulcer. Recurrence rates of patients who smoked, consumed alcohol, and used NSAIDs were significantly higher in those with gastric ulcer recurrence compared to duodenal ulcer recurrence (e.g. 125 of 149 [83.9%] relapsed ulcers recurred at the same or adjacent sites as the previous ulcers). Curative treatment of H. pylori infection is useful in preventing ulcer recurrence. Gastric ulcer is more likely to relapse than duodenal ulcer. Recurrent ulcer tended to recur at the site of the original ulcers.

Systematic review and meta-analysis: Is 1-week proton pump inhibitor-based triple therapy sufficient to heal peptic ulcer?

Article

May 2005

To systematically review the efficacy on ulcer healing of 1-week combination of a proton pump inhibitor plus two antibiotics and to perform a meta-analysis of randomized clinical trials to evaluate whether 7 days of proton pump inhibitor-based triple therapy is sufficient to heal peptic ulcer. Studies where 1-week proton pump inhibitor-based triple therapy was administered to heal peptic ulcer were included. Randomized clinical trials comparing the efficacy on ulcer healing of 7-day proton pump inhibitor-based triple therapy versus this same regimen but prolonging the proton pump inhibitor for several more weeks were included in the meta-analysis. Electronic and manual bibliographical searches were conducted. Meta-analysis was performed combining the odds ratios of the individual studies. Twenty-four studies (2342 patients) assessed ulcer healing with 1-week proton pump inhibitor-based triple therapy. Mean healing rate was 86%, and 95% in Helicobacter pylori-eradicated patients. Six studies (862 patients), were included in the meta-analysis. Mean ulcer healing rate with a 7-day treatment was 91% versus 92% when proton pump inhibitor was prolonged for 2-4 more weeks (odds ratio = 1.11; 95% confidence interval = 0.71-1.74). In patients with peptic ulcer and H. pylori infection, prolonging therapy with proton pump inhibitor after a triple therapy for 7 days with a proton pump inhibitor and two antibiotics is not necessary to induce ulcer healing.

A pilot study to evaluate a new combination therapy for gastric ulcer: Helicobacter pylori eradication therapy followed by gastroprotective treatment with rebamipide

Article

Feb 2006

Controversies remain over the need for antiulcer treatment following 1-week eradication triple therapy for Helicobacter pylori-positive peptic ulcers. The usefulness of combination therapy for gastric ulcers in Japanese patients, which consists of H. pylori eradication followed by gastroprotective therapy with rebamipide, was therefore evaluated. The study was conducted in 52 H. pylori-positive patients with an endoscopically-proven open gastric ulcer. All patients received 1-week triple therapy (lansoprazole, amoxicillin and clarithromycin) followed by 7-week rebamipide therapy. After completion of the combination therapy, all patients underwent evaluation of ulcer healing by endoscopy, gastric ulcer symptoms and H. pylori eradication by rapid urease test and (13)C-urea breath test. The ulcer healing rates were 85.7% (36/42) at 8 weeks, 83.3% (30/36) in eradicated patients and 100% (6/6) in non-eradicated patients. The overall gastrointestinal symptom-free rate improved from 19.0% at baseline to 88.1% at 8 weeks. H. pylori was effectively eradicated in 85.7% (36/42) of patients. The results suggested that the combination therapy for open gastric ulcer was safe, well-tolerated and effective. However, data from a double-blind placebo-controlled study is necessary to confirm these findings.

Rebamipide, a gastro-protective and anti-inflammatory drug, promotes gastric ulcer healing following eradication therapy for Helicobacter pylori in a Japanese population: A randomized, double-blind, placebo-controlled trial

Abstract

No full-text available

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