[Show abstract][Hide abstract] ABSTRACT: We determined the efficacy and safety of pelvic floor myofascial physical therapy compared to global therapeutic massage in women with newly symptomatic interstitial cystitis/painful bladder syndrome.
A randomized controlled trial of 10 scheduled treatments of myofascial physical therapy vs global therapeutic massage was performed at 11 clinical centers in North America. We recruited women with interstitial cystitis/painful bladder syndrome with demonstrable pelvic floor tenderness on physical examination and a limitation of no more than 3 years' symptom duration. The primary outcome was the proportion of responders defined as moderately improved or markedly improved in overall symptoms compared to baseline on a 7-point global response assessment scale. Secondary outcomes included ratings for pain, urgency and frequency, the O'Leary-Sant IC Symptom and Problem Index, and reports of adverse events. We compared response rates between treatment arms using the exact conditional version of the Mantel-Haenszel test to control for clustering by clinical center. For secondary efficacy outcomes cross-sectional descriptive statistics and changes from baseline were calculated.
A total of 81 women randomized to the 2 treatment groups had similar symptoms at baseline. The global response assessment response rate was 26% in the global therapeutic massage group and 59% in the myofascial physical therapy group (p=0.0012). Pain, urgency and frequency ratings, and O'Leary-Sant IC Symptom and Problem Index decreased in both groups during followup, and were not significantly different between the groups. Pain was the most common adverse event, occurring at similar rates in both groups. No serious adverse events were reported.
A significantly higher proportion of women with interstitial cystitis/painful bladder syndrome responded to treatment with myofascial physical therapy than to global therapeutic massage. Myofascial physical therapy may be a beneficial therapy in women with this syndrome.
The Journal of urology 04/2012; 187(6):2113-8. DOI:10.1016/j.juro.2012.01.123 · 4.47 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Bladder pain syndrome/interstitial cystitis is a poorly understood condition that can cause serious disability. We provide the first population based symptom prevalence estimate to our knowledge among United States adult females.
We developed and validated 2 case definitions to identify bladder pain syndrome/interstitial cystitis symptoms. Beginning in August 2007 we telephoned United States households, seeking adult women with bladder symptoms or a bladder pain syndrome/interstitial cystitis diagnosis. Second stage screening identified those subjects who met case definition criteria. Each completed a 60-minute interview on the severity and impact of bladder symptoms, health care seeking and demographics. Data collection ended in April 2009. Using population and nonresponse weights we calculated prevalence estimates based on definitions spanning a range of sensitivity and specificity. We used United States Census counts to estimate the number of affected women in 2006. The random sample included 146,231 households, of which 131,691 included an adult female. Of these households 32,474 reported an adult female with bladder symptoms or diagnosis, of which 12,752 completed the questionnaire.
Based on the high sensitivity definition 6.53% (95% CI 6.28, 6.79) of women met symptom criteria. Based on the high specificity definition 2.70% (95% CI 2.53, 2.86) of women met the criteria. These percentages translated into 3.3 to 7.9 million United States women 18 years old or older with bladder pain syndrome/interstitial cystitis symptoms. Symptom severity and impact were comparable to those of adult women with established diagnoses. However, only 9.7% of the women reported being assigned a bladder pain syndrome/interstitial cystitis diagnosis.
Bladder pain syndrome/interstitial cystitis symptoms are widespread among United States women and associated with considerable disability. These results suggest bladder pain syndrome/interstitial cystitis may be underdiagnosed.
The Journal of urology 06/2011; 186(2):540-4. DOI:10.1016/j.juro.2011.03.132 · 4.47 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To provide a clinical framework for the diagnosis and treatment of interstitial cystitis/bladder pain syndrome.
A systematic review of the literature using the MEDLINE® database (search dates 1/1/83-7/22/09) was conducted to identify peer reviewed publications relevant to the diagnosis and treatment of interstitial cystitis/bladder pain syndrome. Insufficient evidence-based data were retrieved regarding diagnosis and, therefore, this portion of the Guideline is based on Clinical Principles and Expert Opinion statements. The review yielded an evidence base of 86 treatment articles after application of inclusion/exclusion criteria. These publications were used to create the majority of the treatment portion of the Guideline. When sufficient evidence existed, the body of evidence for a particular treatment was assigned a strength rating of A (high), B (moderate) or C (low). Additional treatment information is provided as Clinical Principles and Expert Opinion when insufficient evidence existed. See text and algorithm for definitions, and detailed diagnostic management, and treatment frameworks.
The evidence-based guideline statements are provided for diagnosis and overall management of interstitial cystitis/bladder pain syndrome as well as for various treatments. The panel identified first through sixth line treatments as well as developed guideline statements on treatments that should not be offered.
Interstitial cystitis/bladder pain syndrome is best identified and managed through use of a logical algorithm such as is presented in this Guideline. In the algorithm the panel identifies an overall management strategy for the interstitial cystitis/bladder pain syndrome patient. Diagnosis and treatment methodologies can be expected to change as the evidence base grows in the future.
The Journal of urology 06/2011; 185(6):2162-70. DOI:10.1016/j.juro.2011.03.064 · 4.47 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: We evaluated the efficacy and tolerability of mycophenolate mofetil in patients with treatment refractory interstitial cystitis/painful bladder syndrome.
A total of 210 patients with interstitial cystitis/painful bladder syndrome were to be randomized into a multicenter, placebo controlled trial using a 2:1 randomization. Participants in whom at least 3 interstitial cystitis/painful bladder syndrome specific treatments had failed and who had at least moderately severe symptoms were enrolled in a 12-week treatment study. The primary study end point was the global response assessment. Secondary end points were general and disease specific symptom questionnaires, and voiding diaries.
Only 58 subjects were randomized before a black box warning regarding mycophenolate mofetil safety was issued by the manufacturer in October 2007. The trial was halted, and interim analysis was performed and presented to an independent data and safety monitoring board. Six of the 39 subjects (15%) randomized at study cessation were considered responders for mycophenolate mofetil compared to 3 of 19 controls (16%, p=0.67). Secondary outcome measures reflected more improvement in controls.
In a randomized, placebo controlled trial that was prematurely halted mycophenolate mofetil showed efficacy similar to that of placebo to treat symptoms of refractory interstitial cystitis/painful bladder syndrome. The results of this limited study cannot be used to confirm or refute the hypothesis that immunosuppressive therapy may be beneficial to at least a subgroup of patients with interstitial cystitis/painful bladder syndrome. Despite study termination lessons can be gleaned to inform future investigations.
The Journal of urology 03/2011; 185(3):901-6. DOI:10.1016/j.juro.2010.10.053 · 4.47 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Evidence suggests that the urogenital pain of chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) may be neuropathic.
This randomized, double-blind, placebo-controlled trial was conducted across 10 tertiary care centers in North America to determine whether pregabalin, which has been proved effective in other chronic pain syndromes, is effective in reducing CP/CPPS symptoms. In 2006-2007, 324 men with pelvic pain for at least 3 of the previous 6 months were enrolled in this study. Men were randomly assigned to receive pregabalin or placebo in a 2:1 ratio and were treated for 6 weeks. Pregabalin dosage was increased from 150 to 600 mg/d during the first 4 weeks. The primary outcome was a 6-point decrease in the National Institutes of Health Chronic Prostatitis Symptom Index (NIH-CPSI) total score. Multiple secondary outcomes were assessed.
Of 218 men assigned to receive pregabalin, 103 (47.2%) reported at least a 6-point decrease in the NIH-CPSI total score at 6 weeks compared with 35.8% (38 of 106 men) assigned to receive placebo (P = .07, exact Mantel-Haenszel test, adjusting for clinical sites). Compared with the placebo group, men assigned to receive pregabalin experienced reductions in the NIH-CPSI total score and subscores (P < .05), a higher Global Response Assessment response rate (31.2% and 18.9%; P = .02), and improvement in total McGill Pain Questionnaire score (P = .01). Results for the other outcomes did not differ between groups.
Pregabalin therapy for 6 weeks was not superior to placebo use in the rate of a 6-point decrease (improvement) in the NIH-CPSI total score in men with CP/CPPS.
clinicaltrials.gov Identifier: NCT00371033.
Archives of internal medicine 09/2010; 170(17):1586-93. DOI:10.1001/archinternmed.2010.319 · 17.33 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: No standard case definition exists for interstitial cystitis/painful bladder syndrome for patient screening or epidemiological studies. As part of the RAND Interstitial Cystitis Epidemiology study, we developed a case definition for interstitial cystitis/painful bladder syndrome with known sensitivity and specificity. We compared this definition with others used in interstitial cystitis/painful bladder syndrome epidemiological studies.
We reviewed the literature and performed a structured, expert panel process to arrive at an interstitial cystitis/painful bladder syndrome case definition. We developed a questionnaire to assess interstitial cystitis/painful bladder syndrome symptoms using this case definition and others used in the literature. We administered the questionnaire to 599 women with interstitial cystitis/painful bladder syndrome, overactive bladder, endometriosis or vulvodynia. The sensitivity and specificity of each definition was calculated using physician assigned diagnoses as the reference standard.
No single epidemiological definition had high sensitivity and high specificity. Thus, 2 definitions were developed. One had high sensitivity (81%) and low specificity (54%), and the other had the converse (48% sensitivity and 83% specificity). These values were comparable or superior to those of other epidemiological definitions used in interstitial cystitis/painful bladder syndrome prevalence studies.
No single case definition of interstitial cystitis/painful bladder syndrome provides high sensitivity and high specificity to identify the condition. For prevalence studies of interstitial cystitis/painful bladder syndrome the best approach may be to use 2 definitions that would yield a prevalence range. The RAND Interstitial Cystitis Epidemiology interstitial cystitis/painful bladder syndrome case definitions, developed through structured consensus and validation, can be used for this purpose.
The Journal of urology 03/2010; 183(5):1848-52. DOI:10.1016/j.juro.2009.12.103 · 4.47 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Amitriptyline is frequently used to treat patients with interstitial cystitis/painful bladder syndrome. The evidence to support this practice is derived mainly from a small, single site clinical trial and case reports.
We conducted a multicenter, randomized, double-blind, placebo controlled clinical trial of amitriptyline in subjects with interstitial cystitis/painful bladder syndrome who were naïve to therapy. Study participants in both treatment arms received a standardized education and behavioral modification program. The drug dose was increased during a 6-week period from 10 up to 75 mg once daily. The primary outcome was a patient reported global response assessment of symptom improvement evaluated after 12 weeks of treatment.
A total of 271 subjects were randomized and 231 (85%) provided a global response assessment at 12 weeks of followup. Study participants were primarily women (83%) and white (74%), with a median age of 38 years. In an intent to treat analysis (271) the rate of response of subjects reporting moderate or marked improvement from baseline in the amitriptyline and placebo groups was 55% and 45%, respectively (p = 0.12). Of the subgroup of subjects (207) who achieved a drug dose of at least 50 mg, a significantly higher response rate was observed in the amitriptyline group (66%) compared to placebo (47%) (p = 0.01).
When all randomized subjects were considered, amitriptyline plus an education and behavioral modification program did not significantly improve symptoms in treatment naïve patients with interstitial cystitis/painful bladder syndrome. However, amitriptyline may be beneficial in persons who can achieve a daily dose of 50 mg or greater, although this subgroup comparison was not specified in advance.
The Journal of urology 03/2010; 183(5):1853-8. DOI:10.1016/j.juro.2009.12.106 · 4.47 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The Bladder Pain Syndrome Committee of the International Consultation on Incontinence was assigned the task by the consultation of reviewing the syndrome, formerly known as interstitial cystitis, in a comprehensive fashion. This included the topics of definition, nomenclature, taxonomy, epidemiology, etiology, pathology, diagnosis, symptom scales, outcome assessment, principles of management, specific therapies, and future directions in research. The emphasis was on new information developed since the last consultation 4 years previously. Where possible, existing evidence was assessed and a level of recommendation was developed according to the Oxford system of classification. The consultation decided to refer to the condition as “bladder pain syndrome” (BPS) because the designation is more descriptive of the clinical condition and better fits standard classification taxonomy. Reasonable definitions of BPS include the definition of the ESSIC European group and a slight modification made at a SUFU sponsored Miami meeting in early 2008. Males or females with pain, pressure, or discomfort that they perceive to be related to the bladder with at least one urinary symptom, such as frequency not obviously related to high fluid intake, or a persistent urge to void should be evaluated for possible BPS. The initial assessment consists of a frequency/volume chart, focused physical examination, urinalysis, and urine culture. Urine cytology and cystoscopy are recommended if clinically indicated. Treatment progresses from conservative management through various oral and intravesical therapies, with most surgical therapies reserved for unresponsive cases. Pain management is critical throughout the treatment process. The consultation believes that the disorder is best viewed as one of a group of chronic pain syndromes, rather than as primarily an inflammatory bladder disorder. Recommendations for future research pathways are suggested. Neurourol. Urodynam. 29: 191–198, 2010.
Neurourology and Urodynamics 12/2009; 29(1):191-8. DOI:10.1002/nau.20847 · 2.87 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Benign prostatic hyperplasia (BPH), a common condition among older men, confers its morbidity through potentially bothersome lower urinary tract symptoms. Treatments for BPH include drugs such as alpha-adrenergic receptor blockers and 5-alpha reductase inhibitors, minimally invasive therapies that use heat to damage or destroy prostate tissue, and surgery including transurethral resection of the prostate. Complementary and alternative medicines are gaining popularity in the US. Two phytotherapies commonly used for BPH are extracts of the fruit of Serenoa repens, the Saw palmetto dwarf palm that grows in the Southeastern US, and extracts of the bark of Pygeum africanum, the African plum tree.
The objective of the Complementary and Alternative Medicines for Urological Symptoms (CAMUS) clinical trial is to determine if phytotherapy is superior to placebo in the treatment of BPH.
CAMUS was originally designed as a 3300-participant, four-arm trial of S. repens, P. africanum, an alpha-adrenergic blocking drug, and placebo with time to clinical progression of BPH, a measure of long-term efficacy, as the primary endpoint. Before enrollment started, a randomized, double-blind, placebo-controlled, single institution clinical trial showed that S. repens at the usual dose did not demonstrate any benefit over placebo with respect to symptom relief at 1 year. Consequently, the focus of CAMUS shifted from evaluating long-term efficacy to determining if any short-term (6-18 months) symptom relief could be achieved with increasing doses of S. repens, the phytotherapy most commonly used in the US for BPH.
Results are anticipated in 2011.
Trial design occurs in an environment of continually evolving information. In this case, emerging results from another trial suggested that a study of long-term efficacy was premature, and that an effective dose and preparation of S. repens had to be established before proceeding to a long-term clinical trial.
[Show abstract][Hide abstract] ABSTRACT: In men with chronic prostatitis-chronic pelvic pain syndrome, treatment with alpha-adrenergic receptor blockers early in the course of the disorder has been reported to be effective in some, but not all, relatively small randomized trials.
We conducted a multicenter, randomized, double-blind, placebo-controlled trial to evaluate the efficacy of alfuzosin, an alpha-adrenergic receptor blocker, in reducing symptoms in men with chronic prostatitis-chronic pelvic pain syndrome. Participation in the study required diagnosis of the condition within the preceding 2 years and no previous treatment with an alpha-adrenergic receptor blocker. Men were randomly assigned to treatment for 12 weeks with either 10 mg of alfuzosin per day or placebo. The primary outcome was a reduction of at least 4 points (from baseline to 12 weeks) in the score on the National Institutes of Health Chronic Prostatitis Symptom Index (NIH-CPSI) (range, 0 to 43; higher scores indicate more severe symptoms). A 4-point decrease is the minimal clinically significant difference in the score.
A total of 272 eligible participants underwent randomization, and in both study groups, 49.3% of participants had a decrease of at least 4 points in their total NIH-CPSI score (rate difference associated with alfuzosin, 0.1%; 95% confidence interval, -11.2 to 11.0; P=0.99). In addition, a global response assessment showed similar response rates at 12 weeks: 33.6% in the placebo group and 34.8% in the alfuzosin group (P=0.90). The rates of adverse events in the two groups were also similar.
Our findings do not support the use of alfuzosin to reduce the symptoms of chronic prostatitis-chronic pelvic pain syndrome in men who have not received prior treatment with an alpha-blocker. (ClinicalTrials.gov number, NCT00103402.)
New England Journal of Medicine 07/2009; 359(25):2663-73. DOI:10.1056/NEJMoa0803240 · 55.87 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: We determined the feasibility of conducting a randomized clinical trial designed to compare 2 methods of manual therapy (myofascial physical therapy and global therapeutic massage) in patients with urological chronic pelvic pain syndromes.
We recruited 48 subjects with chronic prostatitis/chronic pelvic pain syndrome or interstitial cystitis/painful bladder syndrome at 6 clinical centers. Eligible patients were randomized to myofascial physical therapy or global therapeutic massage and were scheduled to receive up to 10 weekly treatments of 1 hour each. Criteria to assess feasibility included adherence of therapists to prescribed therapeutic protocol as determined by records of treatment, adverse events during study treatment and rate of response to therapy as assessed by the patient global response assessment. Primary outcome analysis compared response rates between treatment arms using Mantel-Haenszel methods.
There were 23 (49%) men and 24 (51%) women randomized during a 6-month period. Of the patients 24 (51%) were randomized to global therapeutic massage, 23 (49%) to myofascial physical therapy and 44 (94%) completed the study. Therapist adherence to the treatment protocols was excellent. The global response assessment response rate of 57% in the myofascial physical therapy group was significantly higher than the rate of 21% in the global therapeutic massage treatment group (p = 0.03).
We judged the feasibility of conducting a full-scale trial of physical therapy methods and the preliminary findings of a beneficial effect of myofascial physical therapy warrants further study.
The Journal of urology 07/2009; 182(2):570-80. DOI:10.1016/j.juro.2009.04.022 · 4.47 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To determine risk factors for, and long-term effects of, glycemic control on urinary incontinence among women with type 1 diabetes enrolled in the Epidemiology of Diabetes Interventions and Complications study.
The Diabetes Control and Complications Trial (1982-1993) cohort follow-up, Epidemiology of Diabetes Interventions and Complications trial, began in 1994. In 2004, the female participants (n = 550) completed a self-administered questionnaire on incontinence. Our primary outcome was weekly or greater incontinence, overall and by type. Multivariate regression models were used to determine independent predictors of weekly urinary incontinence, both overall and by type.
Overall, 38% of women reported any incontinence and 17% reported weekly or greater incontinence. An increasing body mass index (odds ratio 1.1, 95% confidence interval 1.1-1.2) was significantly associated with weekly incontinence, overall and by type. Advancing age and >/=2 urinary tract infections in the previous year were associated with weekly urge incontinence (odds ratio 1.4, 95% confidence interval 1.0-2.0 per 5 years, and odds ratio 4.9, 95% confidence interval 1.8-13.5, respectively). Weaker evidence was seen for increased risk with age for overall weekly incontinence (22% per 5 years, P = .06) and stress incontinence (21% per 5 years, P = .08).
Urinary incontinence is common among women with type 1 diabetes and the risk factors, including advancing age, increased weight, and previous urinary tract infection, are important. Weight reduction and the treatment of urinary tract infections might have the additional benefit of preventing incontinence or reducing its severity.
[Show abstract][Hide abstract] ABSTRACT: The Urinary Incontinence Treatment Network (UITN) was established in 2000 as a multi-disciplinary, multi-institutional network by the National Institute for Diabetes, Digestive, and Kidney Diseases (NIDDK) to investigate treatments for urinary incontinence in women.
Over 8 years this network composed of urologists, urogynecologists, geriatricians, behavioral psychologists, physical therapists, nurses, epidemiologists, social scientists and statisticians from nine academic sites and a Data Coordinating Center has been effective in designing and completing prospective randomized clinical trials for treatments of urinary incontinence in women.
Two major clinical trials have been completed and a third has completed recruitment. The focus of the completed trials was a comparison of surgical methods to treat stress urinary incontinence whereas the third examined the potential benefit of combined behavioral intervention and antimuscarinic drug therapy to eliminate the need for long-term use of drug therapy alone to manage urge urinary incontinence. The scientific output of the network measured by abstracts, original papers and presentations demonstrates the productivity of the network.
Many unique challenges are posed by a multi-disciplinary team located at sites across the United States undertaking several clinical trials. This review presents some of the logistics, barriers, tactics, and strategies used to create this successful clinical trials network focused on urinary incontinence.
Neurourology and Urodynamics 03/2009; 28(3):170-6. DOI:10.1002/nau.20653 · 2.87 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: We compared the prevalence, level of bother and effect on daily activities of urinary incontinence among women with type 1 diabetes enrolled in the Epidemiology of Diabetes Interventions and Complications study to a population based sample of women with normal glucose.
We performed a cross-sectional analysis of women with type 1 diabetes and normal glucose tolerance using 2 study populations. The Diabetes Control and Complications Trial cohort followup, Epidemiology of Diabetes Interventions and Complications, began in 1994. In 2004 women participants (550) completed a self-administered questionnaire on urinary incontinence. Our primary outcome was weekly or greater incontinence, overall and by type. Prevalence of urinary incontinence was compared to a subgroup of women with normal glucose in the 2001 to 2002 National Health and Nutrition Examination Survey (NHANES).
Overall 65% of women with type 1 diabetes reported any urinary incontinence (17% reported weekly incontinence). Nearly 40% of these women were greatly bothered by their incontinence and 9% believed it affected their day-to-day activities. Women with type 1 diabetes had a nearly 2-fold greater prevalence of weekly urge incontinence compared to those without diabetes in the NHANES cohort (8.8% vs 4.5%, p = 0.01).
Urinary incontinence is common in women with type 1 diabetes and the prevalence of weekly urge incontinence is far greater compared to that in women with normal glucose levels. Moreover, the prevalence of urinary incontinence in women with type 1 diabetes was greater than that of neuropathy, retinopathy and nephropathy. These findings highlight the importance of screening for urinary incontinence among women with type 1 diabetes. Studies examining factors associated with urinary incontinence in women with type 1 diabetes are warranted.
The Journal of urology 02/2009; 181(3):1224-30; discussion 1230. DOI:10.1016/j.juro.2008.11.024 · 4.47 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Although diabetes is known to result in lower urinary tract symptoms (LUTS) in men, it remains unclear if glycemic control can mitigate urinary symptoms. We studied how diabetic characteristics are related to LUTS in the men who completed the urological assessment component (UroEDIC) of the Epidemiology of Diabetes Interventions and Complications (EDIC) follow-up study of the Diabetes Control and Complications Trial (DCCT) participants.
Study participants were men who completed the UroEDIC questionnaire at the year 10 DCCT/EDIC follow-up examination, which included data on genitourinary tract function and the American Urological Association Symptom Index (AUASI). Analyses were conducted to assess how treatment arm and diabetes characteristics were associated with LUTS using logistic regression.
Of the 591 men who completed the AUASI questions, nearly 20% (n = 115) had AUASI scores in the moderate to severe category for LUTS (AUASI score >or=8). No associations were observed between LUTS and treatment arm, or A1C levels at the DCCT baseline or end-of-study or at the year 10 EDIC (UroEDIC) examination. Of the diabetes complications studied, only erectile dysfunction at the UroEDIC examination was associated with LUTS.
These data from the UroEDIC cohort do not support the assumption that intensive glycemic control results in decreased lower urinary tract symptom severity in men with type 1 diabetes. This result may be due to a true lack of effect, or it may be due to other factors, for example, the relatively young age of the cohort.
Diabetes care 02/2009; 32(4):664-70. DOI:10.2337/dc07-2375 · 8.42 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Because of the frequency of urinary tract infections in children, off-label use of antimicrobial prophylaxis is often the usual treatment of children with vesicoureteral reflux, and such use is increasingly being called into question; hence, a definitive study to determine the value of antimicrobial prophylaxis with regard to the recurrence of urinary tract infection and the incidence of renal scarring is essential. The currently recommended follow-up procedures (repeated urine cultures, renal and genitourinary imaging, antimicrobial therapy and prophylaxis, as well as other factors including cleanliness, adequate bladder and bowel emptying, and compliance with protocols) are expensive (in terms of time, attention to detail, and cost) and cumbersome. Such recommendations should be evidence-based.
[Show abstract][Hide abstract] ABSTRACT: Our goal is to determine if antimicrobial prophylaxis with trimethoprim/sulfamethoxazole prevents recurrent urinary tract infections and renal scarring in children who are found to have vesicoureteral reflux after a first or second urinary tract infection. DESIGN, PARTICIPANTS, AND METHODS: The Randomized Intervention for Children With Vesicoureteral Reflux (RIVUR) study is a double-blind, randomized, placebo-controlled trial. Six hundred children aged 2 to 72 months will be recruited from both primary and subspecialty care settings at clinical trial centers throughout North America. Children who are found to have grades I to IV vesicoureteral reflux after the index febrile or symptomatic urinary tract infection will be randomly assigned to receive daily doses of either trimethoprim/sulfamethoxazole or placebo for 2 years. Scheduled follow-up contacts include in-person study visits every 6 months and telephone interviews every 2 months. Biospecimens (urine and blood) and genetic specimens (blood) will be collected for future studies of the genetic and biochemical determinants of vesicoureteral reflux, recurrent urinary tract infection, renal insufficiency, and renal scarring.
The primary outcome is recurrence of urinary tract infection. Secondary outcomes include time to recurrent urinary tract infection, renal scarring (assessed by dimercaptosuccinic acid scan), treatment failure, renal function, resource utilization, and development of antimicrobial resistance in stool flora.
The RIVUR study will provide useful information to clinicians about the risks and benefits of prophylactic antibiotics for children who are diagnosed with vesicoureteral reflux after a first or second urinary tract infection. The data and specimens collected over the course of the study will allow researchers to better understand the pathophysiology of recurrent urinary tract infection and its sequelae.