Evaluation of Peri-Operative Antibiotic Strategy Versus Antibiotic Sparing in Asymptomatic Bacteriuria with Botulinum Toxin A in MS and SCI Patients

The primary objective of this study is to demonstrate the non-inferiority of an antibiotic sparing strategy compared to a peri-operative antibiotic strategy regarding the occurrence of symptomatic urinary tract infection in patients with asymptomatic bacteriuria undergoing intra-vesical botulinum toxin A injections. This evaluation is conducted in patients with multiple sclerosis or spinal cord injury receiving clean intermittent catheterization. The secondary objectives include:

• Comparison of additional efficacy and safety outcomes between the two antibiotic strategies.
• Identification of risk factors associated with post-injection symptomatic urinary tract infection.
• Conducting an ad-hoc health-economic analysis to compare the antibiotic sparing strategy with current peri-operative recommendations.

The sponsor did not provide the total number of participants. The study population consists of male and female individuals aged 18 years or older diagnosed with multiple sclerosis or spinal cord injury. Participants must present with detrusor overactivity resulting in urinary incontinence that has proven refractory to anti-muscarinic therapy. Eligible subjects require clean intermittent self-catheterization as their sole bladder management method and must have demonstrated efficacy from prior intravesical botulinum toxin A injections. Inclusion requires the presence of asymptomatic bacteriuria, defined by a bacteriuria threshold of ≥ 10² CFU/mL during preoperative urine analysis.

This prospective, multicenter, open-label, non-inferiority randomized clinical trial is designed to compare an antibiotic sparing strategy with a standard peri-operative antibiotic strategy. The study focuses on patients with multiple sclerosis or spinal cord injury who present with asymptomatic bacteriuria and detrusor overactivity while utilizing clean intermittent self-catheterization. Following a screening visit that includes a urine analysis to confirm bacteriuria, participants undergo intra-vesical botulinum toxin A injections. The primary objective is to evaluate the occurrence of symptomatic urinary tract infection within 6 weeks after the injection. Research activities include follow-up assessments at 6 weeks to monitor adverse events, cystometric capacity, and bladder function via a bladder diary. The estimated duration of the trial, encompassing recruitment and study activities, is from September 2025 to September 2027.

The experimental treatments consist of several antimicrobial agents. Amoxicillin is administered as a dispersible tablet at a dose of 3 g via the oral route. Ofloxacin is provided as a scored film coated tablet at a dose of 400 mg administered orally. Ceftriaxone is utilized in two formulations: a solution for injection containing 1 g of ceftriaxone and lidocaine hydrochloride monohydrate administered via intramuscular injection, and a 1 g solution for injection administered via the intravenous route. Levofloxacin is administered as a 500 mg film-coated tablet orally. Amoxicillin and clavulanic acid are administered as a 500 mg/62.5 mg film-coated tablet at a total dose of 3000 mg orally. Aztreonam is administered as a 2 g powder for solution for injection via intramuscular injection. Pivmecillinam hydrochloride is administered as an 800 mg film-coated tablet orally. Trimethoprim is administered as a 300 mg tablet orally. Ciprofloxacin is administered as a 1000 mg film-coated tablet orally. Sulfamethoxazole and trimethoprim are administered as a 1600 mg tablet orally. Fosfomycin trometamol is administered as a 3 g oral solution in sachet form. Cefixime is administered as a 400 mg film-coated tablet orally.

The primary efficacy endpoint is the rate of patients experiencing symptomatic urinary tract infection within 6 weeks following intra-vesical botulinum toxin A injection. This is defined according to the National Institute on Disability and Rehabilitation Research as significant bacteriuria accompanied by tissue invasion and a resultant tissue response presenting with signs or symptoms of infection.

Secondary endpoints assessed at the 6-week timepoint include:

• Rate of febrile and non-febrile symptomatic urinary tract infection.
• Rate of symptomatic urinary tract infection requiring antibiotic therapy.
• Rate of adverse events and emergency unit admissions, categorized by their relation to the injection.
• Rate of non-scheduled hospitalization, categorized by its relation to the injection.
• Maximal cystometric capacity, evaluated via urodynamics.
• Presence and characteristics of detrusor overactivity, including volume at the first uninhibited contraction and maximal detrusor pressure.
• Clean intermittent self-catheterization frequency, urgency episodes, urinary incontinence episodes, and functional bladder capacity, as recorded in a 3-day bladder diary.