Antibiotic Strategy and Asymptomatic Bacteriuria in the Context of Intra-vesical Botulinum Toxin A Injections.

Study Overview
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Brief Summary
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The study aims to demonstrate that the thrifty antibiotic strategy applied to MS or SCI patients with asymptomatic bacteriuria prior to BoNTA intravesical injections does not increase the rate of symptomatic post-injection UTIs compared to the current peri-operative antibiotic strategy. Patients included in the study will be randomized in two balanced-parallel groups, 4 days (+/- 2 days) before intra-vesical BoNTA injections. Group 1: Experimental group: Sparing antibiotic strategy No antibiotic therapy will be administered during the peri-operative period. Group 2: Control group: Recommendations - Peri-operative antibiotic strategy An antibiotic therapy will be administered during the peri-operative period. The antibiotic will be selected according to the type of bacteria isolated and the antibiotic susceptibility testing, and started two days before and pursued until two days following intra-vesical BoNTA injections. The main objective is to demonstrate the non-inferiority of antibiotic saving strategy compared to peri-operative antibiotic strategy (current recommendations) for occurrence of symptomatic UTI after intra-vesical BoNTA injections in the management of asymptomatic bacteriuria (AB) among multiple sclerosis (MS) and spinal cord injured (SCI) patients undergoing clean intermittent self-catheterization (CISC).

Official Title
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Assessment of the Interest of a Peri-operative Antibiotic Strategy Applied to Patients With Asymptomatic Bacteriuria Undergoing Intra-vesical Botulinum Toxin A Injections

Conditions
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Urinary Tract Disease

Intervention / Treatment
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* Procedure: Intra-vesical BoNTA injections


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: MS or SCI (traumatic or non-traumatic) Refractory OAB and/or DO (failure, intolerance or contra-indication to anti-muscarinic therapy) Treated with intra-vesical botulinum toxin A injections having proved efficacy CISC as the exclusive bladder management AB on pre-operative urine analysis (performed 10 days (+/- 2 days) before intra-vesical BoNTA injections) Exclusion of morphologic urinary tract abnormalities considered as a risk factor for recurrent symptomatic UTI. Exclusion Criteria: Having already participated to the study Augmentation cystoplasty Bladder compliance disorders (<20 mL/cmH2O) Ongoing cyclic antibiotic therapy Ongoing corticosteroid therapy Modification of immunosuppressive or immunomodulatory therapy in the 3 months before inclusion (MS patients) Antibiotic therapy in the month before inclusion Surgical procedure in the 3 months before and the 6 weeks following inclusion Symptomatic UTI at the time of inclusion Associated neurologic disease Pregnancy or breast feeding Individuals especially in need of protection No informed consent Patients incapable to follow the trial, e.g. because of language problems, psychiatric disorders, dementia and so on Immunocompromised patients

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: Sparing antibiotic strategy<br>No antibiotic therapy will be administered during the peri-operative period | Procedure: Intra-vesical BoNTA injections<br>* Intra-vesical BoNTA injections will be performed according to the protocol currently applied by the department. They will be performed in the operating room or in the outpatient clinic under strict asepsis, including the wearing of sterile gloves by the surgeon associated with an antiseptic brushing of the patient and the establishment of sterile fields. A rigid or a flexible cystoscope will be used. After the introduction of the cystoscope under visual control, complete bladder emptying will be performed. The bladder will be filled again, slowly and at low pressure to allow the bladder mucosa to expand. BoNTA (BOTOX® 200 U) will be diluted as follows: BOTOX® 200 U: in 30 mL of saline solution The solution obtained will be injected all along the bladder wall, sparing the trigone in 20 (BOTOX® 200 U) points using a Bonee®-type needle. A complete bladder emptying will be performed at the end of the procedure.<br>|
| Sham Comparator: Peri-operative antibiotic strategy<br>Recommendations - An antibiotic therapy will be administered during the peri-operative period. The antibiotic will be selected according to the type of bacteria isolated and the antibiotic susceptibility testing, and started two days before and pursued until two days following intra-vesical BoNTA injections | Procedure: Intra-vesical BoNTA injections<br>* Intra-vesical BoNTA injections will be performed according to the protocol currently applied by the department. They will be performed in the operating room or in the outpatient clinic under strict asepsis, including the wearing of sterile gloves by the surgeon associated with an antiseptic brushing of the patient and the establishment of sterile fields. A rigid or a flexible cystoscope will be used. After the introduction of the cystoscope under visual control, complete bladder emptying will be performed. The bladder will be filled again, slowly and at low pressure to allow the bladder mucosa to expand. BoNTA (BOTOX® 200 U) will be diluted as follows: BOTOX® 200 U: in 30 mL of saline solution The solution obtained will be injected all along the bladder wall, sparing the trigone in 20 (BOTOX® 200 U) points using a Bonee®-type needle. A complete bladder emptying will be performed at the end of the procedure.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rate of patients with symptomatic UTI occurring within the 6 weeks following the injections. | Symptomatic UTI will be defined according to the National Institute on Disability and Rehabilitation Research (NIDRR, 1992) as a significant bacteriuria with tissue invasion and resultant tissue response with signs and/or symptoms of UTI | During the 6 weeks following the injections | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rate of patients with febrile symptomatic UTI occurring within the 6 weeks following BoNTA injections.occurring within the 6 weeks following the injections. | Symptomatic UTI will be defined according to the National Institute on Disability and Rehabilitation Research (NIDRR, 1992) as a significant bacteriuria with tissue invasion and resultant tissue response with signs and/or symptoms of UTI | During the 6 weeks following the injections | 
| Rate of patients with non-febrile symptomatic UTI occurring within the 6 weeks following BoNTA injections | Symptomatic UTI will be defined according to the National Institute on Disability and Rehabilitation Research (NIDRR, 1992) as a significant bacteriuria with tissue invasion and resultant tissue response with signs and/or symptoms of UTI | During the 6 weeks following the injections | 
| Rate of patients with symptomatic UTI within the 6 weeks following BoNTA injections finally needing the administration of an antibiotic therapy. | Symptomatic UTI will be defined according to the National Institute on Disability and Rehabilitation Research (NIDRR, 1992) as a significant bacteriuria with tissue invasion and resultant tissue response with signs and/or symptoms of UTI | During the 6 weeks following the injections | 
| Rate of patients with complication (other than symptomatic UTI) related to* BoNTA injections occurring within the 6 weeks following the injections. | Any complication leading to an admission in an emergency unit : macroscopic hematuria persisting for more than 48 hours after injections, painful catheterization lasting more than 48 hours after intra-vesical BoNTA injections, pseudo-botulism, botulism. | During the 6 weeks following the injections | 
| Rate of patients with complication not related to** BoNTA injections occurring within the 6 weeks following the injections. | Any complication not listed in the complications related to the injections | During the 6 weeks following the injections | 
| Rate of patients with admission to an emergency unit related to* BoNTA injections occurring within the 6 weeks following the injections. | Any complication leading to an admission in an emergency unit : macroscopic hematuria persisting for more than 48 hours after injections, painful catheterization lasting more than 48 hours after intra-vesical BoNTA injections, pseudo-botulism, botulism. | During the 6 weeks following the injections | 
| Rate of patients with admission to an emergency unit not related** to BoNTA occurring within the 6 weeks following the injections | Any complication not listed in the complications related to the injections. | During the 6 weeks following the injections | 
| Rate of patients with admission in a non-scheduled hospitalization related to* BoNTA injections occurring within the 6 weeks following the injections. | Any complication leading to an admission in an emergency unit : macroscopic hematuria persisting for more than 48 hours after injections, painful catheterization lasting more than 48 hours after intra-vesical BoNTA injections, pseudo-botulism, botulism. | During the 6 weeks following the injections | 
| Rate of patients with admission in a non-scheduled hospitalization not related to* BoNTA injections occurring within the 6 weeks following the injections. | Any complication not listed in the complications related to the injections. | During the 6 weeks following the injections | 
| Maximal cystometric capacity (MCC) | Maximal cystometric capacity (MCC) measured during the urodynamic multichannel study | 6 weeks after BoNTA injections. | 
| Rate of patients with detrusor overactivity (non-voiding detrusor contractions during feeling phase) | Detrusor overactivity measured during the urodynamic multichannel study | 6 weeks after BoNTA injections. | 
| Number of CISC per day | Number of CISC measured on a 3-day bladder diary | 6 weeks after BoNTA injections. | 
| Number of urgency episodes per day | Number of urgency episodes measured on a 3-day bladder diary | 6 weeks after BoNTA injections. | 
| Number of urinary incontinence episodes per day | Number of urinary incontinence episodes measured on a 3-day bladder diary | 6 weeks after BoNTA injections. | 
| Functional bladder capacity | Functional bladder capacity measured on a 3-day bladder diary | 6 weeks after BoNTA injections. | 
| Identify risk factors of in-hospital postoperative symptomatic UTI |  | 6 weeks after BoNTA injections. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Neurogenic lower urinary tract dysfunction, Clean Intermittent Self Catheterization, Asymptomatic bacteriuria, Botulinum toxin A, Sparing antibiotic strategy, Safety