Methenamine Hippurate Versus Trimethoprim in the Prevention of Recurrent UTIs

Study Overview
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Brief Summary
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Several methods are available for use in the prevention of recurrent urinary tract infections (UTIs) over the past few decades. These methods include suppressive antibiotics, estrogen cream, methenamine hippurate, d-mannose, cranberry, probiotics, and vitamin C. Of these, the majority of the literature is in favor of use of suppressive antibiotics for preventing UTIs. However, this data is now about 10 years old. Increasing use of antibiotics over the years has lead to increased resistance of bacteria. In addition, long-term antibiotic use has several adverse effects, some life-threatening. There is recent literature evaluating the use of several of the alternatives to suppressive antibiotics with mixed results. A comparative study of the efficacy of methenamine hippurate to suppressive antibiotics is lacking in the current literature. Several early partly-randomized trials done with methenamine hippurate have shown promising results, but are only as recent as 1987. The primary objective of this prospective, randomized study is to determine whether there is a significant difference in the prevention of recurrent UTIs when given either methenamine hippurate or daily suppressive antibiotics. The secondary objective of this study is to determine how well patients are able to tolerate each of these medications and what adverse effects are observed in a given 1 year time period. The long-term goals of this study are to find an alternative to using suppressive antibiotics, potentially with a lower adverse effect profile and less of the dangers of long term antibiotic use. Finding an alternative to suppressive antibiotics would also tackle the issue of antibiotic resistance.

Detailed Description
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Hypothesis: The hypothesis of this study is that the group taking trimethoprim will have a lower recurrence rate than those taking methenamine hippurate based on the literature. The investigators aim to identify to what degree that difference is and whether or not it is an acceptable difference given the greater degree of an antibiotic resistance. Objectives: The primary objective of this prospective, randomized study is to determine whether there is a significant difference in the prevention of recurrent UTIs when given either methenamine hippurate or daily suppressive antibiotics independent of vaginal estrogen use. The secondary objective of this study is to determine how well patients are able to tolerate each of these medications and what adverse effects are observed in a 1 year time period. Specific Aims: Identify if there is a differential impact on prevention of recurrent UTIs when treated with either trimethoprim or methenamine hippurate in a 6 and 12 month period. Identify adverse reactions in each group. Determine whether or not estrogen has a more additive effect to trimethoprim or methenamine hippurate in post-menopausal women. Identify how well tolerated the study medications are and whether or not the size of the pills or the frequency of taking them prevents patients from continuing therapy.

Official Title
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Methenamine Hippurate Versus Trimethoprim in the Prevention of Recurrent UTIs

Conditions
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Urinary Tract Infections, Recurrent

Intervention / Treatment
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* Drug: Trimethoprim
* Drug: Methenamine hippurate


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: recurrent UTI: at least 2 in the past 6 months or 3 in past year (culture positive) must have been symptomatic with dysuria, urgency, frequency, suprapubic pain, hematuria, malodorous urine treated for last UTI and negative urine culture on entry into study English speaking Exclusion Criteria: pregnancy urinary tract abnormalities (eg kidney stones) acute pyelonephritis renal insufficiency or failure known allergy to medications prophylaxis for post-coital recurrent UTIs

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 99 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Patients diagnosed with recurrent urinary tract infections are recruited into this study.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Patients with recurrent UTIs arm 1<br>Patients are randomized to receive methenamine hippurate in one arm if they are diagnosed with recurrent urinary tract infections. | Drug: Methenamine hippurate<br>* antiseptic used in the prevention of recurrent UTIs. Estrogen cream may be prescribed if the patient is post-menopausal (but not as a part of this study).<br>* Other names: Hiprex;|
| Active Comparator: Patients with recurrent UTIs arm 2<br>Patients are randomized to receive trimethoprim in the other arm if they are diagnosed with recurrent urinary tract infections. | Drug: Trimethoprim<br>* suppressive antibiotic. Estrogen cream may be prescribed if the patient is post-menopausal (but not as a part of this study).<br>* Other names: Trimpex;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to Subsequent Infection as Defined From Time of Treatment Initiation to Recurrence of UTI | Patients will be advised to follow up with any symptoms of a recurrence or at 6 and 12 month intervals if symptom-free. | up to 12 months | 
| Recurrent UTI | The number of patient who had a recurrence of UTI within 12 months | up to 12 months | 
| Number of Infections | The number of infections at a 12 month follow up time period as defined by symptoms and positive urine culture. | up to 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Adverse Effects | The percentage of patients complaining of adverse effects of each medication, including dyspepsia, dysuria, rash, pruritus, nausea, epigastric pain, vomiting, glossitis, taste changes, fever, and photosensitivity. | up to 12 months | 
| Morisky Medication Adherence Survey | Morisky Medication Adherence Scale-8 (MMAS-8). Patient tolerability of medications using a tolerability survey. Minimum and maximum scores are 0 and 8 respectively. 0 means no adherence and 8 is maximal adherence. Low adherence corresponds to a score less than 6, medium adherence is between 6 and <8, and 8 is high adherence. | up to 12 months | 
| Bacterial Infection Prevalence and Types | Urine cultures and sensitivities for positive urine cultures | up to 12 months |