Cotrimoxazole Prophylaxis in Transurethral Resection or Greenlight Laser Vaporisation of the Prostate (CITrUS)

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

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.

Study Overview

• Status: Completed
• Conditions: Antimicrobial Prophylaxis in Prostate Surgery
• Intervention / Treatment: Drug: oral applications of Placebo; Drug: oral applications of TMP/SMX 800/160 mg (Nopil forte® tablets)

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

• Study Type: Interventional
• Enrollment (Actual): 728
• Phase: Phase 4

Contacts and Locations

Study Locations

• Switzerland
  • Aarau, Switzerland, 5001
    • Kantonsspital Aarau, Department of Urology
  • Basel, Switzerland, 4031
    • University Hospital Basel, Division of Infectious Diseases and Hospital Epidemiology
  • Liestal, Switzerland, 4410
    • Kantonsspital Baselland, Department of Urology
  • Zürich, Switzerland, 8091
    • University Hospital Zurich, Department of Urology
  • Basel Stadt
    • Basel, Basel Stadt, Switzerland, 4058
      • St. Claraspital, Department of Urology

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Group A; Single-dose Trimethoprim (TMP)/sulfamethoxazole (SMX, i.e. Cotrimoxazole) perioperative as two ampoules of TMP/SMX 400/80 mg (Bactrim Inf Konz®) solved in 250 ml sodium chloride short infusion followed by five oral applications of placebo (lactose tablet; Fagron Gesellschaft mit beschränkter Haftung (GmbH) & Co.KG) at the evening of the surgery and thereafter twice daily on day 1 and 2 after surgery while the patient is in hospital.	Drug: oral applications of Placebo; five oral applications of Placebo at the evening of the surgery and thereafter twice daily on day 1 and 2 after surgery while the patient is in hospital.
Active Comparator: Group B; 3-day application with TMP/SMX (i.e. Cotrimoxazole): Preoperatively as two ampoules of TMP/SMX 400/80mg (Bactrim Inf Konz®) solved in 250 ml sodium chloride short infusion, followed by five oral applications of TMP/SMX 800/160 mg (Nopil forte® tablets) at the evening of the surgery and thereafter twice daily on day 1 and 2 after surgery while the patient is in hospital.	Drug: oral applications of TMP/SMX 800/160 mg (Nopil forte® tablets); five oral applications of TMP/SMX 800/160 mg (Nopil forte® tablets) at the evening of the surgery and thereafter twice daily on day 1 and 2 after surgery while the patient is in hospital.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Symptomatic UrinaryTract Infection (UTI)	Symptomatic UTI (based on clinical diagnosis) treated with antimicrobial agents	within 30 days after randomization

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Symptomatic UTI by measured bacteriuria	measured bacteriuria of ≥105 cfu/ml treated with antimicrobial agents (key secondary outcome)	within 30 days after randomization
Symptomatic cystitis (based on clinical diagnosis)	Symptomatic cystitis (based on clinical diagnosis)	within 30 days after randomization
Symptomatic epididymitis (based on clinical diagnosis)	Symptomatic epididymitis (based on clinical diagnosis)	within 30 days after randomization
Symptomatic pyelonephritis (based on clinical diagnosis)	Symptomatic pyelonephritis (based on clinical diagnosis)	within 30 days after randomization
Symptomatic prostatitis (based on clinical diagnosis)	Symptomatic prostatitis (based on clinical diagnosis)	within 30 days after randomization
Symptomatic urethritis (based on clinical diagnosis)	Symptomatic urethritis (based on clinical diagnosis)	within 30 days after randomization
Urosepsis (based on clinical diagnosis)	Urosepsis (based on clinical diagnosis)	within 30 days after randomization
Prescription of antibiotics (for any reason)	Prescription of antibiotics (for any reason)	within 30 days after randomization
Prescribed defined daily doses (DDD) of antibiotics (cumulative sum of DDD) day 30)	Prescribed defined daily doses (DDD) of antibiotics (cumulative sum of DDD)	within 30 days after randomization
Asymptomatic bacteriuria of ≥105 cfu/ml treated with antimicrobial agents	Asymptomatic bacteriuria of ≥105 cfu/ml treated with antimicrobial agents	within 30 days after randomization
Detection of multidrug-resistant bacteria in Urine culture	Detection of multidrug-resistant bacteria in Urine culture	within 30 days after randomization
Any Clostridium difficile-associated infection	Any Clostridium difficile-associated infection	within 30 days after randomization
Duration of catheterisation (cumulative sum of days between randomisation and end of catheterisation or day 30)	Duration of catheterisation (cumulative sum of days between randomisation and end of catheterisation or day 30)	within 30 days after randomization
Duration of hospital stay (cumulative sum of Hospital days between randomisation and day 30)	Duration of hospital stay (cumulative sum of Hospital days between randomisation and day 30)	within 30 days after randomization
Duration of intensive care unit (ICU) stay (cumulative sum of ICU days between randomisation and day 30)	Duration of intensive care unit stay (cumulative sum of ICU days between randomisation and day 30)	within 30 days after randomization
Re-hospitalisation (within 30 days after randomisation)	Re-hospitalisation (within 30 days after randomisation)	within 30 days after randomization
Change of International Prostate Symptom Score (prior to randomisation and at day 30 after randomisation)	Change of International Prostate Symptom Score (prior to randomisation and at day 30 after randomisation)	within 30 days after randomization
Change of Quality of life Score (prior to randomisation and at day 30 after randomisation)	Change of Quality of life Score (prior to randomisation and at day 30 after randomisation)	within 30 days after randomization
All-cause mortality	All-cause mortality	within 30 days after randomization
Total adverse events	Total adverse events	within 30 days after randomization
Total serious adverse events	Total serious adverse events	within 30 days after randomization

Collaborators and Investigators

• Sponsor: University Hospital, Basel, Switzerland
• Collaborators: Swiss National Science Foundation
• Investigators: Principal Investigator: Andreas Widmer, Prof.,MD,Dr., Division of Infectious Diseases and Hospital Epidemiology

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start (Actual): October 29, 2018
• Primary Completion (Actual): October 31, 2022
• Study Completion (Actual): October 31, 2022

Study Registration Dates

• First Submitted: August 14, 2018
• First Submitted That Met QC Criteria: August 14, 2018
• First Posted (Actual): August 16, 2018

Study Record Updates

• Last Update Posted (Actual): August 16, 2024
• Last Update Submitted That Met QC Criteria: August 15, 2024
• Last Verified: August 1, 2024

More Information

Terms related to this study

• Keywords: Transurethral resection of the prostate; Greenlight Laser Vaporisation of the Prostate; Cotrimoxazole Prophylaxis
• Other Study ID Numbers: 2018-0104; me17Widmer

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No