Greenberg ER, Anderson GL, Morgan DR, et al.. 14-day triple, 5-day concomitant, and 10-day sequential therapies for Helicobacter pylori infection in seven Latin American sites: a randomised trial

SWOG Statistical Center, Cancer Research and Biostatistics, Seattle, WA 98101-1468, USA.
The Lancet (Impact Factor: 45.22). 08/2011; 378(9790):507-14. DOI: 10.1016/S0140-6736(11)60825-8
Source: PubMed

ABSTRACT Evidence from Europe, Asia, and North America suggests that standard three-drug regimens of a proton-pump inhibitor plus amoxicillin and clarithromycin are significantly less effective for eradication of Helicobacter pylori infection than are 5-day concomitant and 10-day sequential four-drug regimens that include a nitroimidazole. These four-drug regimens also entail fewer antibiotic doses than do three-drug regimens and thus could be suitable for eradication programmes in low-resource settings. Few studies in Latin America have been done, where the burden of H pylori-associated diseases is high. We therefore did a randomised trial in Latin America comparing the effectiveness of four-drug regimens given concomitantly or sequentially with that of a standard 14-day regimen of triple therapy.
Between September, 2009, and June, 2010, we did a randomised trial of empiric 14-day triple, 5-day concomitant, and 10-day sequential therapies for H pylori in seven Latin American sites: Chile, Colombia, Costa Rica, Honduras, Nicaragua, and Mexico (two sites). Participants aged 21-65 years who tested positive for H pylori by a urea breath test were randomly assigned by a central computer using a dynamic balancing procedure to: 14 days of lansoprazole, amoxicillin, and clarithromycin (standard therapy); 5 days of lansoprazole, amoxicillin, clarithromycin, and metronidazole (concomitant therapy); or 5 days of lansoprazole and amoxicillin followed by 5 days of lansoprazole, clarithromycin, and metronidazole (sequential therapy). Eradication was assessed by urea breath test 6-8 weeks after randomisation. The trial was not masked. Our primary outcome was probablity of H pylori eradication. Our analysis was by intention to treat. This trial is registered with, registration number NCT01061437.
1463 participants aged 21-65 years were randomly allocated a treatment: 488 were treated with 14-day standard therapy, 489 with 5-day concomitant therapy, and 486 with 10-day sequential therapy. The probability of eradication with standard therapy was 82·2% (401 of 488), which was 8·6% higher (95% adjusted CI 2·6-14·5) than with concomitant therapy (73·6% [360 of 489]) and 5·6% higher (-0·04% to 11·6) than with sequential therapy (76·5% [372 of 486]). Neither four-drug regimen was significantly better than standard triple therapy in any of the seven sites.
Standard 14-day triple-drug therapy is preferable to 5-day concomitant or 10-day sequential four-drug regimens as empiric therapy for H pylori infection in diverse Latin American populations.
Bill & Melinda Gates Foundation, US National Institutes of Health.

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    • "They obtained better eradication rates with 14-day sequential therapy when compared to the other two regimens, indicating the importance of the duration of the treatment. On the other hand, a large Latin American trial [18] found a 5.6% higher eradication rate with a 14-day triple therapy when compared to a 10-day sequential therapy. That was a multicenter study of seven sites and sequential therapy was not significantly better in any of the sites. "
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    ABSTRACT: Sequential treatment scheme has been developed to overcome resistance problem in H. pylori eradication and favorable results have been obtained. This study compared the results of standard triple therapy with a sequential schema consisting of pantoprazole, amoxicillin, clarithromycin, and metronidazole in a high anti-microbial resistance setting. This retrospective study included subjects that underwent standard or sequential eradication treatment after a diagnosis of biopsy-documented H. pylori infection. Patients either received pantoprazole 40 mg bid, amoxicillin 1000 mg bid and clarithromycin 500 mg bid (PAC) for 10 days, or pantoprazole 40 mg bid and amoxicillin 1000 mg bid (PA) for the first 5 days of the treatment period and were then given pantoprazole 40 mg bid, clarithromycin 500 mg bid, and metronidazole 500 mg bid (PCM) in the remaining 5 days. Eradication was tested using urea breath test. The two treatment groups did not differ with regard to H. pylori eradication rate for both ITT population (63.9% versus 71.4% for standard and sequential therapy respectively, P = 0.278) and per protocol population (65.9% versus 74.1% for standard and sequential therapy respectively, P = 0.248). Although a sequential treatment appears to represent a plausible alternative, our findings suggest that alternative schedules may be required in certain populations to achieve higher success rates.
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    • "Subsequent meta-analysis including reports published after October 2008 and including studies from other countries have reported eradication rates of the ST to be of 80.6%.19 In addition, studies from Latin America showed that ST was not better than TT.20 These findings suggest that the relative effectiveness of ST regimen varies between geographical regions. "
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    ABSTRACT: Sequential therapy (ST) for Helicobacter pylori infection in countries other than Korea has shown higher eradication rates than triple therapy (TT). The aim of this study was to evaluate the efficacy of ST in Korea by performing a meta-analysis. We performed a comprehensive literature search on the efficacy of ST as a first-line therapy. The odds ratios (ORs) of eradicating H. pylori infection after ST compared with TT were pooled. Pooled estimates of the eradication rates of ST and TT were also calculated. A total of six studies provided data on 1,759 adult patients. The ORs for the intention to treat (ITT) and the per-protocol (PP) eradication rate were 1.761 (95% confidence interval [CI], 1.403 to 2.209) and 1.966 (95% CI, 1.489 to 2.595). Pooled estimates of the ITT and PP eradication rate were 79.4% (95% CI, 76.3% to 82.2%) and 86.4% (95% CI, 83.5% to 88.8%), respectively, for the ST group, and 68.2% (95% CI, 62.1% to 73.8%) and 78.9% (95% CI, 68.9% to 81.7%), respectively, for the TT group. Although ST presented a higher eradication rate than TT in Korea, the pooled eradication rates were lower than expected. Further studies are needed to validate ST as a first-line treatment for H. pylori in Korea.
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    • "Autor y año Calv et 2000 Cata lano 2000 Chan 2001 Choi 2011 Greenberg 2011 Kim 2011 Kongcha yanu n 2 011a Kongchayanun 2011b Kwon 2011a Kwon 2011b Molina-Infante 2011 Moon 2011 Nagahara 200 0 Nagahara 200 1 Neville 1999 Okada 1998 Okada 1999 Tor os 2011 Tre iber 1998 Tre iber 2002a Tre iber 2002b Wu 2010 "
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