Comparison of Methods for Prevention of Urinary Tract Infection Following Botox Injection

Comparison of Methods for Prevention of Urinary Tract Infection Following Botox Injection: a Non-Inferiority Trial

Injection of OnabotulinumtoxinA (BTX-A) into the bladder is a widely used treatment option for patients with overactive bladder who have failed medical therapy. Urinary tract infection is the most common side effect of this procedure and therefore antibiotics are given around the time of injection in order to prevent these events. While antibiotics are commonly given at the time of injection, the duration of these antibiotic regimens are variable. The investigators propose a study to investigate different antibiotic protocols and their affect on the rate of urinary tract infection after injection.

Study Overview

• Status: Terminated
• Conditions: Overactive Bladder; Urinary Tract Infections
• Intervention / Treatment: Procedure: Injection of OnabotulinumtoxinA (BTX-A); Drug: Extended Antibiotics; Drug: Periprocedural Antibiotics

Detailed Description

Intravesical injection of OnabotulinumtoxinA (BTX-A) is a widely practiced third line therapy for non-neurogenic overactive bladder (OAB). However, a paucity of data exists regarding urinary tract infections (UTI), the most common adverse event following injection. The investigators propose a randomized, controlled cross-over trial to investigate the utility of commonly practiced antibiotic protocols and simultaneously derive information regarding risk factors for post-procedural UTIs and their affect on treatment efficacy.

The investigators plan to initiate a prospective, randomized non-inferiority cross-over trial, in which a participant receives peri-procedural antibiotics exclusively at the time of one injection, and then at a subsequent injection, completes a three-day course of antibiotics post-operatively in addition to the peri-procedural dose. Enrollment is planned to achieve a total of 68 participants. Participants will be evaluated at 3 weeks and 3 months following injection to identify adverse events and treatment success. Inter-injection time will be measured and used a surrogate for efficacy over multiple injections.

These results, in addition to filling a void in current literature regarding the increasingly utilized treatment with BTX-A, have the potential to modify clinical practice regarding antibiotic use and decrease rates of adverse events. The means to stratify patients based on their specific risk of UTI may be used to facilitate antibiotic stewardship and improve patient outcomes.

• Study Type: Interventional
• Enrollment (Actual): 22
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • Tennessee
    • Nashville, Tennessee, United States, 37232
      • Vanderbilt University Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion criteria:

• ≥ 18 years of age
• Medication refractory OAB, identified per American Urological Association guidelines

Exclusion criteria:

• Post void residual urine >150ml on two occasions
• Untreated, symptomatic UTI
• Comorbid neurological conditions, including spinal cord injury, systemic neurologic illnesses (i.e. multiple sclerosis, Parkinson's disease) or central nervous system disease (i.e. brain tumor, stroke)
• Prior pelvic irradiation
• Current or prior bladder malignancy
• Hematuria lacking a clinically appropriate evaluation
• Chronic indwelling or intermittent catheterization

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: Periprocedural Antibiotics Only; Patients receive a one-time dose of antibiotics at the time of injection, prior to injection.	Procedure: Injection of OnabotulinumtoxinA (BTX-A); Patients will receive injection of OnabotulinumtoxinA (BTX-A) per standard clinic practice protocol. All patients will undergo injection per a standardized protocol of 1ml injection per site at a concentration of 10 units/ml.; Drug: Periprocedural Antibiotics; One the day of injection, after eligibility is determined and consent obtained, research staff will refer to the randomization list to determine to which arm the patient is randomized. Patients randomized to the "Procedural Antibiotics Only" arm will receive a single dose of trimethoprim/sulfamethoxazole (800/160mg) peri-procedurally at the time of the first injection.; Other Names: trimethoprim/sulfamethoxazole
Experimental: Extended Antibiotics; Patients receive a peri-procedural dose of antibiotics and an extended (3-day) course of antibiotics to be taken post-procedurally.	Procedure: Injection of OnabotulinumtoxinA (BTX-A); Patients will receive injection of OnabotulinumtoxinA (BTX-A) per standard clinic practice protocol. All patients will undergo injection per a standardized protocol of 1ml injection per site at a concentration of 10 units/ml.; Drug: Extended Antibiotics; Patients randomized to the "Extended Antibiotics" arm will receive one dose of trimethoprim/sulfamethoxazole peri-procedurally and additionally be prescribed trimethoprim/sulfamethoxazole twice daily for three days. Patients who are allergic will receive amoxicillin/clavulanic acid (875/125mg) twice daily for three days. If allergic to both of the above antibiotics, patients will receive 100mg nitrofurantoin BID for three days. For their second injection, they will receive peri-procedural antibiotics only.; Other Names: trimethoprim/sulfamethoxazole; Drug: Periprocedural Antibiotics; One the day of injection, after eligibility is determined and consent obtained, research staff will refer to the randomization list to determine to which arm the patient is randomized. Patients randomized to the "Procedural Antibiotics Only" arm will receive a single dose of trimethoprim/sulfamethoxazole (800/160mg) peri-procedurally at the time of the first injection.; Other Names: trimethoprim/sulfamethoxazole

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Post Procedural- Urinary Tract Infection	Number of participants with post procedural- urinary tract infection 3 weeks after injections, measured by a urine culture and defined as a urine culture with >10^5 bacterial colonies in the setting of urinary symptoms.	3 weeks post-injection

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Urinary Retention	Number of participants with urinary retention > 250 cc post-procedurally as measured by post void residual volume using a bladder scanner in clinic.	3 weeks post-injection
Recurrent Urinary Tract Infection	Number of participants with 3 or greater post procedural- urinary tract infection after injections, measured by a urine culture and defined as a urine culture with >10^5 bacterial colonies in the setting of urinary symptoms.	3 weeks post injection

Collaborators and Investigators

• Sponsor: Vanderbilt University Medical Center
• Collaborators: Society of Urodynamics, Female Pelvic Medicine and Urogenital Reconstruction; The Allergan Foundation
• Investigators: Principal Investigator: Melissa Kaufman, MD, PhD, Vanderbilt University Medical Center

Study record dates

Study Major Dates

• Study Start (Actual): July 1, 2018
• Primary Completion (Actual): June 1, 2022
• Study Completion (Actual): June 1, 2022

Study Registration Dates

• First Submitted: March 13, 2018
• First Submitted That Met QC Criteria: April 24, 2018
• First Posted (Actual): April 26, 2018

Study Record Updates

• Last Update Posted (Actual): November 2, 2023
• Last Update Submitted That Met QC Criteria: October 31, 2023
• Last Verified: October 1, 2023

More Information

Terms related to this study

• Keywords: Onabotulinumtoxin
• Additional Relevant MeSH Terms: Pathologic Processes; Urologic Diseases; Urinary Bladder Diseases; Lower Urinary Tract Symptoms; Urological Manifestations; Disease Attributes; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Urinary Bladder, Overactive; Infections; Communicable Diseases; Urinary Tract Infections; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Peripheral Nervous System Agents; Cholinergic Agents; Enzyme Inhibitors; Membrane Transport Modulators; Cytochrome P-450 Enzyme Inhibitors; Antiprotozoal Agents; Antiparasitic Agents; Acetylcholine Release Inhibitors; Neuromuscular Agents; Antitubercular Agents; Antimalarials; Folic Acid Antagonists; Anti-Dyskinesia Agents; Anti-Infective Agents, Urinary; Cytochrome P-450 CYP2C8 Inhibitors; Botulinum Toxins, Type A; abobotulinumtoxinA; Anti-Bacterial Agents; Antibiotics, Antitubercular; Trimethoprim; Sulfamethoxazole
• Other Study ID Numbers: 00011112222

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