Overactive Bladder, Urinary Tract Infections
Conditions
Keywords
Onabotulinumtoxin
Brief summary
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.
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.
Interventions
DRUGPeriprocedural 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.
DRUGExtended 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.
PROCEDUREInjection 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.
Sponsors
The Allergan Foundation
Society of Urodynamics, Female Pelvic Medicine & Urogenital Reconstruction
Vanderbilt University Medical Center
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Post Procedural- Urinary Tract Infection | 3 weeks post-injection | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Urinary Retention | 3 weeks post-injection | Number of participants with urinary retention \> 250 cc post-procedurally as measured by post void residual volume using a bladder scanner in clinic. |
| Recurrent Urinary Tract Infection | 3 weeks post injection | 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. |
Countries
United States
Participant flow
Recruitment details
Enrollment halted
Pre-assignment details
22 participants were randomized. Data is reported only for the 17 participants who fully completed both injections and all follow-up visits.
Participants by arm
| Arm | Count |
|---|---|
| Periprocedural Antibiotics Only, Then Extended Antibiotics All patients will undergo an intravesical injection of OnabotulinumtoxinA (Botox ®, BTX-A) per a standardized protocol of 1ml injection per site at a concentration of 10 units/ml at Visit 1 and a second injection at visit 2.
Participants will also receive:
* Periprocedural Antibiotics Only: At Visit 1, patients will receive a single dose of trimethoprim/sulfamethoxazole (800/160mg) peri-procedurally
* Extended antibiotics: At Visit 2, patients will receive one dose of trimethoprim/sulfamethoxazole periprocedurally 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 | 6 |
| Extended Antibiotics, Then Periprocedural Antibiotics Only All patients will undergo an intravesical injection of OnabotulinumtoxinA (Botox ®, BTX-A) per a standardized protocol of 1ml injection per site at a concentration of 10 units/ml at Visit 1 and a second injection at visit 2.
Participants will also receive:
* Extended antibiotics: At Visit 1, patients will receive one dose of trimethoprim/sulfamethoxazole periprocedurally 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
* Periprocedural Antibiotics Only: At Visit 2, patients will receive a single dose of trimethoprim/sulfamethoxazole (800/160mg) peri-procedurally | 11 |
| Total | 17 |
Baseline characteristics
| Characteristic | Periprocedural Antibiotics Only, Then Extended Antibiotics | Extended Antibiotics, Then Periprocedural Antibiotics Only | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 3 Participants | 4 Participants | 7 Participants |
| Age, Categorical Between 18 and 65 years | 3 Participants | 7 Participants | 10 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 6 Participants | 11 Participants | 17 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 2 Participants | 2 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 6 Participants | 9 Participants | 15 Participants |
| Region of Enrollment United States | 6 participants | 11 participants | 17 participants |
| Sex: Female, Male Female | 5 Participants | 11 Participants | 16 Participants |
| Sex: Female, Male Male | 1 Participants | 0 Participants | 1 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 17 | 0 / 17 |
| other Total, other adverse events | 0 / 17 | 0 / 17 |
| serious Total, serious adverse events | 0 / 17 | 0 / 17 |
Outcome results
Primary
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.
Time frame: 3 weeks post-injection
Population: Data is reported only for the 17 participants who fully completed both injections and all follow-up visits.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Periprocedural Antibiotics Only, Then Extended Antibiotics | Post Procedural- Urinary Tract Infection | Visit 1: 3 weeks post-injection | 0 participants |
| Periprocedural Antibiotics Only, Then Extended Antibiotics | Post Procedural- Urinary Tract Infection | Visit 2: 3 weeks post-injection | 0 participants |
| Extended Antibiotics, Then Periprocedural Antibiotics Only | Post Procedural- Urinary Tract Infection | Visit 1: 3 weeks post-injection | 1 participants |
| Extended Antibiotics, Then Periprocedural Antibiotics Only | Post Procedural- Urinary Tract Infection | Visit 2: 3 weeks post-injection | 2 participants |
Secondary
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.
Time frame: 3 weeks post injection
Population: Data is reported only for the 17 participants who fully completed both injections and all follow-up visits.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Periprocedural Antibiotics Only, Then Extended Antibiotics | Recurrent Urinary Tract Infection | Visit 1: 3 weeks post-injection | 0 participants |
| Periprocedural Antibiotics Only, Then Extended Antibiotics | Recurrent Urinary Tract Infection | Visit 2: 3 weeks post-injection | 0 participants |
| Extended Antibiotics, Then Periprocedural Antibiotics Only | Recurrent Urinary Tract Infection | Visit 1: 3 weeks post-injection | 0 participants |
| Extended Antibiotics, Then Periprocedural Antibiotics Only | Recurrent Urinary Tract Infection | Visit 2: 3 weeks post-injection | 0 participants |
Secondary
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.
Time frame: 3 weeks post-injection
Population: Data is reported only for the 17 participants who fully completed both injections and all follow-up visits.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Periprocedural Antibiotics Only, Then Extended Antibiotics | Urinary Retention | Visit 1: 3 weeks post-injection | 1 participants |
| Periprocedural Antibiotics Only, Then Extended Antibiotics | Urinary Retention | Visit 2: 3 weeks post-injection | 0 participants |
| Extended Antibiotics, Then Periprocedural Antibiotics Only | Urinary Retention | Visit 1: 3 weeks post-injection | 3 participants |
| Extended Antibiotics, Then Periprocedural Antibiotics Only | Urinary Retention | Visit 2: 3 weeks post-injection | 3 participants |