Nitrofurantoin Administration for the Prevention of Short-Term Catheter Associated Urinary Tract Infection After Pelvic Surgery

Study Overview
=================
Brief Summary
-----------------
The specific aim of this randomized double-blind placebo-controlled trial is to evaluate the efficacy of administration of nitrofurantoin prophylaxis after catheter discontinuation for the prevention of catheter-associated urinary tract infections in patients with postoperative short-term catheterization following pelvic reconstructive surgery and/or urinary incontinence surgery. Patients that undergo pelvic organ prolapse and/or urinary incontinence surgery and fail their post-operative voiding trial will be included in the study. Upon successfully passing and in-office voiding trial at the time of catheter removal, they will be randomized to either nitrofurantoin 100mg twice daily or an identical appearing placebo capsule twice daily for 5 days following catheter removal. The primary outcome will be the treatment of clinically suspected and/or culture-proven UTI within 30 days of surgery. Secondary outcomes include adverse events associated with nitrofurantoin use and medication compliance. Primary and secondary outcomes will be evaluated with Student t test and chi squared or Fisher exact test as appropriate. Assuming a decrease in symptomatic UTIs attributable to nitrofurantoin prophylaxis from 32% to 14%, with 80% power, and a two-sided alpha of 0.05, we should recruit a total of 164 patients.

Detailed Description
-----------------
Urinary tract infections (UTI) are the most common hospital-acquired infections, accounting for nearly 30% of cases of nosocomial infections and affecting nearly 1 million people per year. Following pelvic reconstructive and urinary incontinence surgery, UTIs are one of the most common complications with a risk between 8.9%-34%. The baseline risk of UTI associated with pelvic floor surgery ranges between 5-35%, increasing greatly with catheterization. Postoperative voiding dysfunction and incomplete bladder emptying is common following pelvic reconstructive and incontinence surgeries, with incidence ranging from 2.5 % to 31%. As a result, these women may have additional catheterization for a short period of time, which increases the risk of UTI. There is a 15-20% risk of developing a postoperative UTI with short-term catheterization, even if the catheter remains in place for merely 24 hours. The risk of UTI increases 5-10% each day the catheter is left in place. Numerous studies have been conducted to evaluate different prophylactic antibiotic regimens to help decrease the rate of postoperative catheter-associated UTIs. Many of these studies have shown precedent for the use of antibiotic prophylaxis. Nitrofurantoin has been evaluated as a prophylactic regimen for use during short-term catheterization. These studies had favorable results, decreasing the incidence of UTI postoperatively. Although there are a few studies showing favorable results for the use of prophylactic nitrofurantoin during catheterization after pelvic surgery, the optimal timing of antibiotic administration and length of dosing regimen is not well defined. The American Urological Association (AUA) recommends empiric antibiotic treatment at the time of external urinary catheter removal in patients with risk factors, such as tobacco use, advanced age, and anatomic abnormalities of the urinary tract. The AUA Panel does cite that bacteriuria in the setting of noninfectious urinary tract disease is a risk factor for bacteremia, and, thus, prophylactic antibiotic treatment at time the of catheter removal may be indicated. The AUA does recommend empiric antibiotic treatment at the removal of an external urinary catheter in patients with risk factors. However, there is no standardization concerning the type of antibiotic to be used or treatment duration. Although there are a few studies showing favorable results for use of nitrofurantoin during catheterization after pelvic surgery, there are no clearly defined recommendations regarding its use for urinary tract infection prevention after catheter removal. Therefore, the objective of our study is to examine the effects of administration of nitrofurantoin therapy at the time of Foley catheter removal for the prevention of catheter-associated UTI in patients undergoing POP and/or urinary incontinence surgery. Primary Objective: To evaluate the efficacy of administration of nitrofurantoin prophylaxis after catheter discontinuation for the prevention of catheter-associated urinary tract infections in patients with postoperative short-term catheterization following pelvic reconstructive surgery. The primary outcome will be the treatment of clinically suspected and/or culture-proven UTI within 30 days of surgery. Secondary Objective: To evaluate adverse outcomes related to study medications in each group and to evaluate medication compliance Null Hypothesis: The null hypothesis is that the administration of nitrofurantoin will not reduce the rate of UTI compared with placebo.

Official Title
-----------------
Nitrofurantoin Administration for the Prevention of Short-Term Catheter Associated Urinary Tract Infection After Pelvic Surgery (NAUTICA): A Randomized Controlled Trial

Conditions
-----------------
Catheter-Associated Urinary Tract Infection

Intervention / Treatment
-----------------
* Drug: Nitrofurantoin 100 MG
* Drug: Placebo Oral Tablet


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Age greater than 18 Creatinine clearance greater than 30 ml/min Failed postoperative hospital voiding trial Exclusion Criteria: Pregnant History of glucose-6-phosphate dehydrogenase deficiency History of renal insufficiency, renal transplant, or nephropathy Allergy to nitrofurantoin History of recurrent UTI (defined as greater than two culture-proven infections in six months or three infections in one year) Urinary Tract Infection (UTI) within 14 days one month of surgery Non-English speaking Urinary tract infection while Foley catheter is in place On antibiotic therapy for other non-urological reasons Sustained intraoperative bladder injury requiring prolonged catheterization greater than 5 days Undergoing mesh excision from within the bladder, fistula repair, cystotomy repair, urethral diverticulectomy, sacral neuromodulation, urethral surgery, or any other procedure requiring prolonged catheterization and bladder decompression Placement of a suprapubic catheter Participants that request intermittent self-catheterization Neurologic conditions affecting urinary tract system and normal voiding mechanisms History of hepatic impairment due to prior nitrofurantoin use Inability to provide consent/decisionally impaired More than two in-office voiding trials

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: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Nitrofurantoin<br>Receives twice daily 100mg nitrofurantoin for 5 days following catheter removal | Drug: Nitrofurantoin 100 MG<br>* Patients will receive nitrofurantoin 100mg twice daily by mouth for 5 days<br>|
| Placebo Comparator: Placebo<br>Receives twice daily matching placebo for 5 days following catheter removal | Drug: Placebo Oral Tablet<br>* Matching placebo<br>|

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| UTI | Number of participants with a urinary tract infection in the first 30 days following pelvic reconstructive surgery | within 30 days of surgery | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Adverse Events | Number of participants with an adverse event only related to study drug administration | within 30 days of surgery | 
| Medication Compliance | Compliance assessed by use of a medication diary during treatment period | within 30 days of surgery | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Nitrofurantoin, Prolapse, Pelvic Organ Prolapse, Anti-incontinence procedure, Urinary retention, Urinary Tract Infection, Short-term catheterization