Clinical trial NCT03633643: Cotrimoxazole Prophylaxis in Transurethral Resection or Greenlight Laser Vaporisation of the Prostate
Official title: Single-Dose Versus 3-Day Cotrimoxazole Prophylaxis in Transurethral Resection or Greenlight Laser Vaporisation of the Prostate: A Pragmatic, Multicentre Randomised Placebo Controlled Non-Inferiority Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Antimicrobial Prophylaxis in Prostate Surgery
Keywords: Greenlight Laser Vaporisation of the Prostate
Transurethral resection of the prostate
Cotrimoxazole Prophylaxis
Lead sponsor: University Hospital, Basel, Switzerland
Sponsor class: OTHER
Collaborators: name: Swiss National Science Foundation
First posted: 2018-08-16
Enrollment: 728
Sex: MALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: single-dose application of Cotrimoxazole compared to a 3-day application of Cotrimoxazole
Primary purpose: TREATMENT

Brief summary: The optimal duration of antimicrobial prophylaxis (study medication Cotrimoxazole (Trimethoprim/Sulfamethoxazole)) in transurethral resection of the prostate and Greenlight Laser vaporisation of the prostate is investigated by comparing a guideline-conform single-dose prophylaxis (intervention) versus usual clinical care (i.e. 3-day prophylaxis; control) for prevention of urinary tract infections.

Detailed description: Increasing antimicrobial resistance rates have a substantial impact on morbidity, mortality and healthcare costs and is particularly prevalent among urological patients due to an overuse of antimicrobial agents for therapeutical and prophylactic indications. Transurethral resection of the prostate is one of the most frequently performed urological procedures in Switzerland and a single-dose of antimicrobial prophylaxis is recommended to reduce postoperative urinary tract infections. For photoselective vaporisation of the prostate with the Greenlight Laser, a similar operative alternative, there are currently no international guidelines for antimicrobial prophylaxis.

The optimal duration of antimicrobial prophylaxis in transurethral resection of the prostate and Greenlight Laser vaporisation of the prostate is investigated by comparing a guideline-conform single-dose prophylaxis (intervention) versus usual clinical care (i.e. 3-day prophylaxis; control) for prevention of urinary tract infections.

The study medication Cotrimoxazole (Trimethoprim/Sulfamethoxazole) is a routinely used antimicrobial substance recommended in international and in-house guidelines for antimicrobial prophylaxis and treatment of urinary tract infections. Perioperative antimicrobial prophylaxis will be Cotrimoxazole short infusion in both groups. Postoperative study medication packages consists of either five tablets of placebo or five tablets of Cotrimoxazole (Nopil forte®) 800/160mg using licensed product repacked in a new immediate container which is blinded

Eligibility criteria: Inclusion Criteria:

* Obstructive voiding disorder (e.g. benign prostate hyperplasia, obstructive prostate cancer)
* Planned Transurethral resection of the prostate (TURP) or Greenlight Laser (GL)

Exclusion Criteria:

* Evidence for (catheter associated-) UTI, with or without antibiotic treatment in the last 7 days prior to randomisation.
* Any evidence of a history of positive urine culture (cfu ³105/ml in midstream-urine with no more than two species) and resistance to TMP/SMX in the last 7 days prior to randomisation.
* Known contraindication against study drugs according to the Swissmedic package leaflet (e.g. known liver dysfunction, renal insufficiency; patients with glomerular filtration rate (calculated by the Modification of Diet in Renal Disease (MDRD) or Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) \<30ml/min or dialysis patients will be excluded).
* Antibiotic treatment for any reason within 7 days prior to randomisation
* Indication for Antibiotic prophylaxis (AP) for other reasons (e.g. endocarditis prophylaxis, transplanted patients under systemic immunosuppression).

Primary outcomes:
measure: Symptomatic UrinaryTract Infection (UTI)
timeFrame: within 30 days after randomization
Secondary outcomes:
measure: Symptomatic UTI by measured bacteriuria
timeFrame: within 30 days after randomization
measure: Symptomatic cystitis (based on clinical diagnosis)
timeFrame: within 30 days after randomization
measure: Symptomatic epididymitis (based on clinical diagnosis)
timeFrame: within 30 days after randomization
measure: Symptomatic pyelonephritis (based on clinical diagnosis)
timeFrame: within 30 days after randomization
measure: Symptomatic prostatitis (based on clinical diagnosis)
timeFrame: within 30 days after randomization
measure: Symptomatic urethritis (based on clinical diagnosis)
timeFrame: within 30 days after randomization
measure: Urosepsis (based on clinical diagnosis)
timeFrame: within 30 days after randomization
measure: Prescription of antibiotics (for any reason)
timeFrame: within 30 days after randomization
measure: Prescribed defined daily doses (DDD) of antibiotics (cumulative sum of DDD) day 30)
timeFrame: within 30 days after randomization
measure: Asymptomatic bacteriuria of ≥105 cfu/ml treated with antimicrobial agents
timeFrame: within 30 days after randomization
measure: Detection of multidrug-resistant bacteria in Urine culture
timeFrame: within 30 days after randomization
measure: Any Clostridium difficile-associated infection
timeFrame: within 30 days after randomization
measure: Duration of catheterisation (cumulative sum of days between randomisation and end of catheterisation or day 30)
timeFrame: within 30 days after randomization
measure: Duration of hospital stay (cumulative sum of Hospital days between randomisation and day 30)
timeFrame: within 30 days after randomization
measure: Duration of intensive care unit (ICU) stay (cumulative sum of ICU days between randomisation and day 30)
timeFrame: within 30 days after randomization
measure: Re-hospitalisation (within 30 days after randomisation)
timeFrame: within 30 days after randomization
measure: Change of International Prostate Symptom Score (prior to randomisation and at day 30 after randomisation)
timeFrame: within 30 days after randomization
measure: Change of Quality of life Score (prior to randomisation and at day 30 after randomisation)
timeFrame: within 30 days after randomization
measure: All-cause mortality
timeFrame: within 30 days after randomization
measure: Total adverse events
timeFrame: within 30 days after randomization
measure: Total serious adverse events
timeFrame: within 30 days after randomization
Other outcomes:
Locations:
city: Basel
country: Switzerland
facility: St. Claraspital, Department of Urology
state: Basel Stadt
city: Aarau
country: Switzerland
facility: Kantonsspital Aarau, Department of Urology
city: Basel
country: Switzerland
facility: University Hospital Basel, Division of Infectious Diseases and Hospital Epidemiology
city: Liestal
country: Switzerland
facility: Kantonsspital Baselland, Department of Urology
city: Zürich
country: Switzerland
facility: University Hospital Zurich, Department of Urology
Study officials:
affiliation: Division of Infectious Diseases and Hospital Epidemiology
name: Andreas Widmer, Prof.,MD,Dr.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Speich B, Bausch K, Roth JA, Hemkens LG, Ewald H, Vogt DR, Bruni N, Deuster S, Seifert HH, Widmer AF. Single-dose versus 3-day cotrimoxazole prophylaxis in transurethral resection or greenlight laser vaporisation of the prostate: study protocol for a multicentre randomised placebo controlled non-inferiority trial (CITrUS trial). Trials. 2019 Feb 19;20(1):142. doi: 10.1186/s13063-019-3237-3.