Prophylactic Antibiotics for Urinary Tract Infections After Robot-Assisted Radical Cystectomy

Study Overview
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Brief Summary
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This trial investigates whether a one-month course of preventative (prophylactic) antibiotics helps to reduce urinary tract infections after robot-assisted surgery to remove all of the bladder as well as nearby tissues and organs (radical cystectomy). Urinary tract infections are a common occurrence after robot-assisted radical cystectomy. Antibiotics such as trimethoprim-sulfamethoxazole or nitrofurantoin may prevent or control infections in patients with urinary tract infection and may help improve their response to radical cystectomy. Information gained from this study may help researchers to predict patient complications and identify better ways to manage these complications.

Detailed Description
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PRIMARY OBJECTIVE: I. To determine if the utilization of a prophylactic antibiotic during the postoperative period will decrease the rate of urinary tract infection (UTI) post robot-assisted radical cystectomy. SECONDARY OBJECTIVE: I. To identify pre- and post-operative factors that may be associated with the development of a 90-day UTI following radical cystectomy. OUTLINE: Patients are randomized to 1 of 2 groups. GROUP I (ANTIBIOTIC): Patients receive ertapenem orally (PO), levofloxacin PO, or clindamycin PO induction therapy per standard of care. At the time of full diet, patients receive trimethoprim-sulfamethoxazole PO daily or nitrofurantoin PO daily on days 1-30. Patients complete a drug diary for each day they receive the antibiotic. GROUP II (CONTROL): Patients receive ertapenem PO, levofloxacin PO, or clindamycin PO induction therapy per standard of care. After surgery, patients are followed up to 120 days.

Official Title
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Does Prophylactic Antibiotic Decrease the Rate of Urinary Tract Infection After Robot Assisted Radical Cystectomy

Conditions
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Bladder Carcinoma, Refractory Bladder Carcinoma, Urinary Tract Infection

Intervention / Treatment
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* Drug: Clindamycin
* Other: Diary
* Drug: Ertapenem
* Drug: Levofloxacin
* Drug: Nitrofurantoin
* Drug: Trimethoprim-Sulfamethoxazole


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Any patient that electively chooses to have a cystectomy is eligible to participate in the study. Indications for a person who may undergo a cystectomy include having a diagnosis of muscle-invasive bladder cancer (MIBC) or refractory non-muscle invasive bladder cancer (NMIBC) Any patient that will electively choose to have a robot-assisted radical cystectomy and is able to provide consent Participant or legal representative must understand the investigational nature of this study and sign an Independent Ethics Committee/Institutional Review Board approved written informed consent form prior to receiving any study related procedure Exclusion Criteria: Patients with a history of myasthenia gravis Patients with a history of QT prolongation or taking other drugs that prolong corrected QTc (QTc) should be excluded Patients with renal dysfunction, creatinine clearance (mL/min) < 30 Pregnant or nursing female participants Females who receive a fertile sex sparing robot-assisted radical cystectomy (RARC) Unwilling or unable to follow protocol requirements Patients who receive a prophylactic antibiotic or antibiotic for any other reason prior to discharge Any condition which in the investigator's opinion deems the participant an unsuitable candidate to receive study drug

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Group I (trimethoprim-sulfamethoxazole, nitrofurantoin)<br>Patients receive ertapenem PO, levofloxacin PO, or clindamycin PO induction therapy per standard of care. At the time of full diet, patients receive trimethoprim-sulfamethoxazole PO daily or nitrofurantoin PO daily on days 1-30. Patients complete a drug diary for each day they receive the antibiotic. | Drug: Clindamycin<br>* Given PO<br>* Other names: Cleocin;Other: Diary<br>* Complete drug diary<br>Drug: Ertapenem<br>* Given PO<br>Drug: Levofloxacin<br>* Given PO<br>* Other names: Quixin;Drug: Nitrofurantoin<br>* Given PO<br>* Other names: Macrodantin;Drug: Trimethoprim-Sulfamethoxazole<br>* Given PO<br>* Other names: Uroplus;|
| Active Comparator: Group II (standard of care)<br>Patients receive ertapenem PO, levofloxacin PO, or clindamycin PO induction therapy per standard of care. | Drug: Clindamycin<br>* Given PO<br>* Other names: Cleocin;Drug: Ertapenem<br>* Given PO<br>Drug: Levofloxacin<br>* Given PO<br>* Other names: Quixin;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 90-day urinary tract infection (UTI) status | Will be treated as dichotomous data and will be summarized by group using frequencies and relative frequencies. | At 90 days after surgery | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Identify pre-operative factors associated with the development of UTI | stratified logistic regression models (stratified by antibiotic use) | Up to 120 days after surgery | 
| Development of Clostridium difficile (C Diff) | Will be evaluated in patients who received prophylactic antibiotics. | up to 120 days after surgery | 
| Infections occurring during antibiotic use | To identify which antibiotic is better suited as a prophylactic, comparisons will be made using two-sided Mann-Whitney U and Fisher's exact tests for continuous and categorical variables, respectively. | Up to 120 days after surgery | 
| Identify post operative factors associated with the development of UTI | stratified logistic regression models (stratified by antibiotic use) | Up to 120 days after surgery |