Methenamine Hippurate Versus Trimethoprim in the Prevention of Recurrent UTIs

• ClinicalTrials.gov Identifier: NCT03077711
• Recruitment Status: Active, not recruiting
• First Posted: March 13, 2017
• Last Update Posted: September 5, 2018
• Sponsor: NorthShore University HealthSystem
• Information provided by (Responsible Party): Carolyn Botros, NorthShore University HealthSystem

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Urinary Tract Infections, Recurrent	Drug: Trimethoprim; Drug: Methenamine hippurate	Phase 4

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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 106 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Intervention Model Description: Patients diagnosed with recurrent urinary tract infections are recruited into this study.
• Masking: None (Open Label)
• Primary Purpose: Prevention
• Official Title: Methenamine Hippurate Versus Trimethoprim in the Prevention of Recurrent UTIs
• Actual Study Start Date: June 2016
• Estimated Primary Completion Date: June 2019
• Estimated Study Completion Date: June 2019

Arms and Interventions

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 Name: 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 Name: Trimpex

Outcome Measures

Primary Outcome Measures :

1. Time to subsequent infection as defined from time of treatment initiation to recurrence of UTI [ Time Frame: up to 12 months ]
   Patients will be advised to follow up with any symptoms of a recurrence or at 6 and 12 month intervals if symptom-free.
2. Infection free patients [ Time Frame: up to 12 months ]
   The number of patient infection free after 12 months as defined by no symptoms and negative urine cultures if symptomatic.
3. Number of infections [ Time Frame: up to 12 months ]
   The number of infections in both a 6 month and 12 month follow up time period as defined by symptoms and positive urine culture.

Secondary Outcome Measures :

1. Adverse effects [ Time Frame: up to 12 months ]
   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.
2. Estrogen effect [ Time Frame: up to 12 months ]
   The additive effect of estrogen cream to prevention (which is also a known protective agent to recurrent UTIs in postmenopausal women), which will be determined using logistic regression at the conclusion of the study.
3. Morisky Medication Adherence Survey [ Time Frame: up to 12 months ]
   Patient tolerability of medications using a tolerability survey.
4. Bacterial infection prevalence and types [ Time Frame: up to 12 months ]
   Urine cultures and sensitivities for positive urine cultures

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 99 Years (Adult, Older Adult)
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: Yes

Criteria

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

Contacts and Locations

Locations

United States, Illinois

NorthShore Univeristy HealthSystem

Skokie, Illinois, United States, 60076

Sponsors and Collaborators

NorthShore University HealthSystem

More Information

• Responsible Party: Carolyn Botros, Female Pelvic Medicine and Reconstructive Surgery, NorthShore University HealthSystem
• ClinicalTrials.gov Identifier: NCT03077711 History of Changes
• Other Study ID Numbers: EH16-216
• First Posted: March 13, 2017
• Last Update Posted: September 5, 2018
• Last Verified: September 2018

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No
• 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.

• 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

Additional relevant MeSH terms:

Urinary Tract Infections; Infection; Urologic Diseases; Trimethoprim; Methenamine; Methenamine hippurate; Methenamine mandelate; Anti-Infective Agents, Urinary; Anti-Infective Agents; Renal Agents; Antimalarials; Antiprotozoal Agents; Antiparasitic Agents; Folic Acid Antagonists; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Anti-Dyskinesia Agents; Cytochrome P-450 CYP2C8 Inhibitors; Cytochrome P-450 Enzyme Inhibitors; Anti-Bacterial Agents