Clinical trial NCT02358993: Short-course Methenamine Hippurate for Prevention of Post-operative UTI
Official title: The Efficacy and Cost-effectiveness of a 24-hour Course of metheNamine Hippurate for Preventing Post-Operative Urinary Tract Infection
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Urinary Tract Infections
Catheter-Related Infections
Keywords: Urinary Tract Infections
Catheter-Related Infections
Pelvic Reconstructive Surgery
Urogynecology
Urinary catheterization
Post-operative Infections
Methenamine hippurate
Lead sponsor: University of Pennsylvania
Sponsor class: OTHER
First posted: 2015-02-09
Enrollment: 201
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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.

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.

Primary outcomes:
measure: Treatment of Clinically Suspected UTI - Using Intent to Treat Analysis
timeFrame: 3 weeks post-operative
measure: Treatment of Clinically Suspected UTI - Per Protocol
timeFrame: 3 weeks post-operative
Secondary outcomes:
measure: Number of Participants With Culture-positive Symptomatic UTI
timeFrame: 3 weeks post-operative
measure: Antibiotic Resistance of Culture-positive Symptomatic UTI
timeFrame: 3 weeks post-operative
measure: Cost-effectiveness of Prophylaxis With Methenamine Hippurate for Prevention of Post-operative UTI Compared to Prophylaxis With Fluoroquinolones
timeFrame: 3 weeks post-operative
measure: Prevalence of Side Effects
timeFrame: within 24 hours of administration
Other outcomes:
measure: Rate of UTI Consistent With NHSN Criteria
timeFrame: 3 weeks post-operative
Locations:
city: Philadelphia
country: United States
facility: Hospital of the University of Pennsylvania
state: Pennsylvania
city: Philadelphia
country: United States
facility: Penn Presbyterian Medical Center
state: Pennsylvania
city: Philadelphia
country: United States
facility: Pennsylvania Hospital
state: Pennsylvania
city: Philadelphia
country: United States
facility: Chestnut Hill Hospital
state: Pennsylvania
Study officials:
affiliation: University of Pennsylvania
name: Christine M Chu, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Pennsylvania
name: Lily Arya, MD, MS
role: STUDY_DIRECTOR
affiliation: University of Pennsylvania
name: Daniel Lee, MD
role: PRINCIPAL_INVESTIGATOR
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