Short-course Methenamine Hippurate for Prevention of Post-operative UTI

Study Overview
=================
Brief Summary
-----------------
The investigators will determine the efficacy of an innovative short regimen of methenamine hippurate on prevention of post-operative UTI in patients requiring short-term catheterization after pelvic reconstructive surgery through a single-blind, randomized controlled trial. Primary outcome will be the rate of symptomatic UTI within 3 weeks of catheter removal. The investigators will study cost-effectiveness, antibiotic resistance profiles, and adverse drug effects. Findings may reduce antibiotic use and nosocomial UTIs.

Detailed Description
-----------------
Prevention of post-operative urinary tract infections (UTI) is becoming important for both the individual patient and the health system. Complications of UTI include pyelonephritis and bacteremia, requiring hospitalization and parenteral antibiotics. Additionally, recurrent exposure to antibiotics commonly given for UTIs increases the risk of antibiotic resistance to uropathogens. UTIs also increase economic burdens on the health care system, with each episode costing nearly 600 dollars. UTIs associated with catheterization are particularly costly for hospitals, resulting in decreased hospital quality measures and lack of compensation. This is particularly important after pelvic reconstructive surgery, as reported rates of UTI reach up to 20-25%. Urinary retention requiring short-term indwelling catheterization, common in these women, contributes to the risk of UTIs by increasing the risk of bacteriuria by 5-10% per day and through the dislodging of bacterial colonies during catheter removal. Balancing prevention and resistance and cost is key. A meta-analysis by Marschall et al indicated the benefit of a short dose of antibiotic prophylaxis at catheter removal in general post-surgical patients. However, data is lacking on the effects of daily antibiotic prophylaxis on resistance and cost. A possible alternative to antibiotics presents itself in methenamine hippurate, a urinary antiseptic which forms formaldehyde in the presence of acidic urine. It is relatively inexpensive, and does not induce resistance in vivo. Prior studies have shown that daily use of methenamine can decrease the risk of post-operative UTI. The purpose of our study was to investigate the efficacy of a short course of methenamine hippurate at catheter removal to that of a short course of ciprofloxacin in prevention of UTIs after short-term indwelling catheterization. Additionally, we investigated factors that influence post-operative UTIs, the rate of culture-proven UTIs after prophylaxis, the antibiotic resistance profile of those undergoing prophylaxis, and the cost effectiveness of prophylaxis.

Official Title
-----------------
The Efficacy and Cost-effectiveness of a 24-hour Course of metheNamine Hippurate for Preventing Post-Operative Urinary Tract Infection

Conditions
-----------------
Urinary Tract Infections, Catheter-Related Infections

Intervention / Treatment
-----------------
* Drug: methenamine hippurate
* Drug: Ciprofloxacin


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: female; patients who are able to read and write English; 18 years of age or older; underwent surgery for pelvic organ prolapse, urinary incontinence, or both; require post-operative short-term transurethral catheterization for greater than 24 hours. Exclusion Criteria: patients undergoing surgical intervention for sacral neuromodulation, or mesh excision; patients requiring long-term catheterization secondary to injury to the urinary tract; patients who pass their post-operative trial void and thus, do not require additional catheterization; patients requiring catheterization for less than 24 hours; pregnant patients; patients who are breast-feeding; allergy to methenamine hippurate or fluroquinolones (either ciprofloxacin or levofloxacin); impaired renal or hepatic function; pre-operative urinary retention; patients who are currently using sulfonamides; patients who have severe dehydration; patients using tizanidine; patients sensitive to quinolones class; patients using theophylline; patients with myasthenia gravis; patients with prolongation of QT interval.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
Female

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Methenamine<br>Methenamine hippurate is a medication that exhibits antibacterial activity by converting to formaldehyde in the presence of acidic urine. It is currently FDA approved for the prophylaxis of recurrent urinary tract infections. It has been previously used in studies for prevention of UTI after gynecologic surgery. Dosage will be methenamine hippurate 1g, 1 tablet by mouth every 12 hours for 24 hours (total of two doses), with the first dose taken at least one hour prior to catheter removal. | Drug: methenamine hippurate<br>* A urinary antiseptic used for prevention of UTI<br>* Other names: Hiprex;|
| Active Comparator: Ciprofloxacin<br>Ciprofloxacin is a commonly used antibiotic commonly used for prevention of UTI after catheterization. It belongs to a class of antibiotics known as the fluoroquinolones. Dosage will be ciprofloxacin 500 mg, 1 tablet by mouth every 12 hours for 24 hours (total of two doses), with the first dose taken at least one hour prior to catheter removal. | Drug: Ciprofloxacin<br>* An antibiotic used for treatment and prevention of UTI<br>* Other names: Cipro;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Treatment of Clinically Suspected UTI - Using Intent to Treat Analysis | This is defined as any symptomatic UTI requiring treatment with antibiotics as determined by the development of 2 or more of the following symptoms, in the absence of vaginal symptoms: urinary frequency; urinary urgency; dysuria; fever over 38oC/100.4oF; suprapubic, flank, or back pain; and/or chills. | 3 weeks post-operative | 
| Treatment of Clinically Suspected UTI - Per Protocol | This is defined as any symptomatic UTI requiring treatment with antibiotics as determined by the development of 2 or more of the following symptoms, in the absence of vaginal symptoms: urinary frequency; urinary urgency; dysuria; fever over 38oC/100.4oF; suprapubic, flank, or back pain; and/or chills. | 3 weeks post-operative | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Culture-positive Symptomatic UTI | All patients will be encouraged to submit urine cultures prior to treatment, but this is not always possible. Amongst patients who undergo urine culture as part of standard of care for UTI, the rate of positive cultures will be identified. | 3 weeks post-operative | 
| Antibiotic Resistance of Culture-positive Symptomatic UTI | All patients who submit urine cultures that are positive will have sensitivities performed as per standard care. The prevalence of bacterial species and sensitivities will be collected | 3 weeks post-operative | 
| Cost-effectiveness of Prophylaxis With Methenamine Hippurate for Prevention of Post-operative UTI Compared to Prophylaxis With Fluoroquinolones | Routine costs of prevention of UTI with methenamine hippurate prophylaxis will be compared with costs of prevention of UTI with fluoroquinolone prophylaxis. We plan to capture costs for each direct medical service use, direct non-medical items, and indirect items related to post-operative UTIs in each arm of the trial. | 3 weeks post-operative | 
| Prevalence of Side Effects | Adverse effects from the administration of methenamine and fluoroquinolones will be collected. | within 24 hours of administration | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Urinary Tract Infections, Catheter-Related Infections, Pelvic Reconstructive Surgery, Urogynecology, Urinary catheterization, Post-operative Infections, Methenamine hippurate