Methenamine Hippurate Versus Trimethoprim in the Prevention of Recurrent UTIs

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.

Study Overview

• Status: Completed
• Conditions: Urinary Tract Infections, Recurrent
• Intervention / Treatment: Drug: Methenamine hippurate; Drug: Trimethoprim

Detailed Description

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:

1. 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.
2. Identify adverse reactions in each group.
3. Determine whether or not estrogen has a more additive effect to trimethoprim or methenamine hippurate in post-menopausal women.
4. 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.

• Study Type: Interventional
• Enrollment (Actual): 92
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • Illinois
    • Skokie, Illinois, United States, 60076
      • NorthShore Univeristy HealthSystem

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 97 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: NorthShore University HealthSystem

Study record dates

Study Major Dates

• Study Start (Actual): June 1, 2016
• Primary Completion (Actual): June 21, 2019
• Study Completion (Actual): June 21, 2019

Study Registration Dates

• First Submitted: February 27, 2017
• First Submitted That Met QC Criteria: March 7, 2017
• First Posted (Actual): March 13, 2017

Study Record Updates

• Last Update Posted (Actual): January 14, 2020
• Last Update Submitted That Met QC Criteria: January 10, 2020
• Last Verified: January 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Infections; Urologic Diseases; Disease Attributes; Recurrence; Urinary Tract Infections; Reinfection; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Anti-Bacterial Agents; Cytochrome P-450 Enzyme Inhibitors; Antiprotozoal Agents; Antiparasitic Agents; Antimalarials; Folic Acid Antagonists; Anti-Dyskinesia Agents; Anti-Infective Agents, Urinary; Renal Agents; Cytochrome P-450 CYP2C8 Inhibitors; Trimethoprim; Methenamine; Methenamine hippurate; Methenamine mandelate
• Other Study ID Numbers: EH16-216

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No
• IPD Plan Description: The investigators are currently only recruiting at one institution and only researchers on the original institutional review board will have access to data. Only the principal investigator and research coordinator will have the data to be analyzed.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No