Is Methenamine Prophylaxis for Urinary Tract Infection After Midurethral Sling As Effective As Antibiotic Prophylaxis?

Is Methenamine Prophylaxis for Urinary Tract Infection After Midurethral Sling As Effective As Antibiotic Prophylaxis? a Randomized Controlled Trial

Stress urinary incontinence (SUI) affects at least 40% of women in the United States. Synthetic polypropylene mid-urethral slings (MUS) are the gold standard treatment for SUI. Post-operative urinary tract infections (UTI) are one of the most common complications after MUS placement. Some studies have demonstrated that MUS placement can increase the risk of UTI up to 21-34%.

Post-operative UTI can lead to significant healthcare and patient burden. This additional burden further contributes to an estimated annual cost of $1.6 billion for UTI management in the United States. With increased antibiotic usage, there is simultaneous increase in bacterial resistance leading to treatment refractory UTI.

The investigators prescribe post-operative antibiotics prophylactically for 3 days after MUS placement with or without concurrent pelvic reconstructive surgery based on prior literature recommending post-operative prophylaxis. There is a greater emphasis on limiting antibiotic use given the trend of development of bacterial resistance. There are studies supporting alternatives such as methenamine for recurrent UTI prophylaxis treatment, but there are limited studies evaluating methenamine for UTI prophylaxis after MUS.

Study Overview

• Status: Recruiting
• Conditions: Urinary Tract Infection (Diagnosis)
• Intervention / Treatment: Drug: Methenamine Hippurate 1g BD; Other: Antibiotic prophylaxis

Detailed Description

Synthetic polypropylene mid-urethral slings (MUS) are the gold standard for treatment of stress urinary incontinence (SUI). The most common post-operative complications are urinary tract infection (UTI), bladder injury, bleeding, and mesh erosion. Amongst these complications, post-operative urinary tract infections are the most common complication with incidences up to 21-34%. With high incidences in post-operative UTI, previous studies have shown evidence for the use of prophylactic antibiotics after MUS placement. Previous studies have demonstrated prophylactic antibiotics after MUS placement decreased the incidence of post-operative UTI in the treated groups. While the use of post-operative prophylactic antibiotics may decrease the risk of post-operative UTI, it is essential to consider the broader implication of such antibiotic use.

Along with increased antibiotic use, there is an increase in multidrug resistant uropathogens. This has led to an increased emphasis on antibiotic stewardship to optimize patient care by minimizing the risk of developing antibiotic resistant organisms, preserving effectiveness of currently used antibiotics, and promoting appropriate prescribing practices. There are no studies evaluating post-operative UTI prophylaxis after MUS with methenamine.

Methenamine is a urinary antiseptic that acts when methenamine is converted to ammonia and formaldehyde, which denatures bacterial proteins and nucleic acids. There is no evidence of bacterial resistance to methenamine. Methenamine has been shown to be non-inferior to antibiotic prophylaxis in the setting of recurrent UTI. Methenamine has most commonly been used as long-term UTI prophylaxis treatment, but there are studies demonstrating benefit from short-term methenamine use for prophylaxis.

The investigator's aim is to evaluate whether methenamine is non-inferior to antibiotic prophylaxis after MUS procedure in preventing post-operative UTI.

• Study Type: Interventional
• Enrollment (Estimated): 190
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Rena Ow, MD; Phone Number: 9739717267; Email: rena.ow@atlantichealth.org

Study Locations

• United States
  • New Jersey
    • Morristown, New Jersey, United States, 07928
      • Recruiting
      • Atlantic Health
      • Contact: Rena Ow, MD; Phone Number: 9739717267; Email: rena.ow@atlantichealth.org
      • Contact: Shaun Adair, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

1. Female
2. Age ≥ 18
3. Patients undergoing mid-urethral sling procedure

Exclusion Criteria:

1. Medication intolerance or allergy to study medications
2. Renal impairment with GFR <30
3. Breast feeding
4. Pregnancy
5. Recurrent urinary tract infections
6. Active urinary tract infection
7. Immunosuppressive disease
8. Interstitial cystitis

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
Experimental: Methenamine prophylaxis; Methenamine will be prescribed for urinary tract infection prophylaxis	Drug: Methenamine Hippurate 1g BD; Antibiotic prophylaxis
Active Comparator: Antibiotic prophylaxis; Antibiotic prophylaxis chosen per physician preference	Other: Antibiotic prophylaxis; Antibiotic prophylaxis

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of urinary tract infection	Urinary tract infection (Positive urine culture) within 6 weeks post-operatively after completing 3 days of antibiotics or methenamine	Within 6 weeks after the procedure

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of participants with adverse effects	Adverse effects or side effects of treatment	within 6 weeks after the procedure
Occurrence of additional treatment of UTI	Further treatment antibiotics given to participants	Within 6 weeks after the procedure

Collaborators and Investigators

• Sponsor: Atlantic Health System

Study record dates

Study Major Dates

• Study Start (Actual): January 30, 2025
• Primary Completion (Estimated): July 30, 2027
• Study Completion (Estimated): January 30, 2028

Study Registration Dates

• First Submitted: January 31, 2025
• First Submitted That Met QC Criteria: January 31, 2025
• First Posted (Actual): March 25, 2025

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: February 5, 2025
• Last Verified: January 1, 2025

More Information

Terms related to this study

• Keywords: prophylaxis; urinary tract infection; midurethral sling; methenamine
• Additional Relevant MeSH Terms: Urogenital Diseases; Pathologic Processes; Male Urogenital Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Disease Attributes; Infections; Communicable Diseases; Urinary Tract Infections; Anti-Infective Agents; Anti-Infective Agents, Urinary; Anti-Bacterial Agents; Methenamine; Methenamine hippurate; Methenamine mandelate
• Other Study ID Numbers: 2248168-1

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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