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)

Benjamin Speich, Kathrin Bausch, Jan A Roth, Lars G Hemkens, Hannah Ewald, Deborah R Vogt, Nicole Bruni, Stefanie Deuster, Hans-H Seifert, Andreas F Widmer, Benjamin Speich, Kathrin Bausch, Jan A Roth, Lars G Hemkens, Hannah Ewald, Deborah R Vogt, Nicole Bruni, Stefanie Deuster, Hans-H Seifert, Andreas F Widmer

Abstract

Background: Transurethral resection of the prostate (TURP) and Greenlight laser vaporisation (GL) of the prostate are frequently performed urological procedures. For TURP, a single-dose antimicrobial prophylaxis (AP) is recommended to reduce postoperative urinary tract infections. So far, no international recommendations for AP have been established for GL. In a survey-based study in Switzerland, Germany and Austria, urologists reported routinely extending AP primarily for 3 days after both interventions. We therefore aim to determine whether single-dose AP with cotrimoxazole is non-inferior to 3-day AP with cotrimoxazole in patients undergoing TURP or GL of the prostate.

Methods/design: We will conduct an investigator-initiated, multicentre, randomised controlled trial. We plan to assess the non-inferiority of single-dose AP compared to 3-day AP. The primary outcome is the occurrence of clinically diagnosed symptomatic urinary tract infections which are treated with antimicrobial agents within 30 days after randomisation. The vast majority of collected outcomes will be assessed from routinely collected data. The sample size was estimated to be able to show the non-inferiority of single-dose AP compared to 3-day AP with at least 80% power (1 - β = 0.8) at a significance level of α = 5%, applying a 1:1 randomisation scheme. The non-inferiority margin was determined in order to preserve 70% of the effect of usual care on the primary outcome. For an assumed event rate of 9% in both treatment arms, this resulted in a non-inferiority margin of 4.4% (i.e. 13.4% to 9%). To prove non-inferiority, a total of 1574 patients should be recruited, in order to have 1416 evaluable patients. The study is supported by the Swiss National Science Foundation.

Discussion: For AP in TURP and GL, there is a large gap between usual clinical practice and evidence-based guidelines. If single-dose AP proves non-inferior to prolonged AP, our study findings may help to reduce the duration of AP in daily routine-potentially reducing the risk of emerging resistance and complications related to AP.

Trial registration: Clinicaltrials.gov, NCT03633643 . Registered 16 August 2018.

Keywords: Antibiotic prophylaxis; Greenlight laser vaporisation; Randomised controlled trial; Transurethral resection of prostate; Urinary tract infection.

Conflict of interest statement

Ethics approval and consent to participate

Ethical approval has been obtained from the ethical committees “Nordwest- und Zentralschweiz” and Zürich (reference number 2018–01404). Additionally approval from Swissmedic was obtained (reference number 2018DR4111). The trial was registered on clinicaltrials.gov (NCT03633643). All patients will be informed about the benefits and risks of this study before participating. Furthermore, they will be informed that participation is voluntary and the withdrawal is possible any time without specific reasons. Written informed consent will be obtained from all participating patients.

Consent for publication

All trials results will be published with open access in peer-reviewed journal publications. We intend to publish the study protocol of the CITrUS Trial in a peer reviewed journal. Authorship to publications will be granted according to the rules of the International Committee of Medical Journal Editors (ICMJE).

Competing interests

The authors declare that they have no competing interests.

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Figures

Fig. 1
Fig. 1
Flowchart of study design. GL Greenlight laser vaporisation, iv intravenous, TMP/SMX trimethoprim/sulfamethoxazole (cotrimoxazole), TURP transurethral resection of the prostate
Fig. 2
Fig. 2
Study procedures and assessments. AP antimicrobial prophylaxis, ASA American Society of Anaesthesiologists, BMI body mass index, cfu colony forming units, DDD defined daily doses, ID identification (number), ICU intensive care unit, MRGN multi-resistant Gram-negatives, PSA prostate specific antigen, UTI urinary tract infection. *Between hospital discharge and close-out visit

References

    1. Reich O, Gratzke C, Bachmann A, Seitz M, Schlenker B, Hermanek P, et al. Morbidity, mortality and early outcome of transurethral resection of the prostate: a prospective multicenter evaluation of 10,654 patients. J Urol. 2008;180(1):246–249. doi: 10.1016/j.juro.2008.03.058.
    1. Ruszat R, Wyler S, Forster T, Reich O, Stief CG, Gasser TC, et al. Safety and effectiveness of photoselective vaporization of the prostate (PVP) in patients on ongoing oral anticoagulation. Eur Urol. 2007;51(4):1031–1038. doi: 10.1016/j.eururo.2006.08.006.
    1. Allegranzi B, Bischoff P, de Jonge S, Kubilay NZ, Zayed B, Gomes SM, et al. New WHO recommendations on preoperative measures for surgical site infection prevention: an evidence-based global perspective. Lancet Infect Dis. 2016;16(12):e276–87.
    1. Bonkat G, Pickard R, Bartoletti R, et al. Complete European Association of Urology Guidelines. 2017. EAU Guidelines on Urological Infections. Perioperative antibacterial prophylaxis in urology; pp. 35–39.
    1. Alsaywid BS, Smith GH. Antibiotic prophylaxis for transurethral urological surgeries: systematic review. Urol Ann. 2013;5(2):61–74. doi: 10.4103/0974-7796.109993.
    1. Qiang W, Jianchen W, MacDonald R, Monga M, Wilt TJ. Antibiotic prophylaxis for transurethral prostatic resection in men with preoperative urine containing less than 100,000 bacteria per ml: a systematic review. J Urol. 2005;173(4):1175–1181. doi: 10.1097/01.ju.0000149676.15561.cb.
    1. Berry A, Barratt A. Prophylactic antibiotic use in transurethral prostatic resection: a meta-analysis. J Urol. 2002;167(2 Pt 1):571–577.
    1. Bausch K, Roth JA, Seifert HH, Widmer AF. Overuse of antimicrobial prophylaxis in low-risk patients undergoing transurethral resection of the prostate. Swiss Med Wkly. 2018;148:w14594.
    1. Hargreave TB, Botto H, Rikken GH, Hindmarsh JR, McDermott TE, Mjolnerod OK, et al. European collaborative study of antibiotic prophylaxis for transurethral resection of the prostate. Eur Urol. 1993;23(4):437–443. doi: 10.1159/000474649.
    1. Hargreave TB, Gould JC, Kinninmonth AW, Jeffrey RR, Varma JS, Macintyre CC, et al. A randomized trial of 48 hours of prophylactic cefotaxime versus single dose in transurethral prostatic surgery. J Antimicrob Chemother. 1984;14(Suppl B):263–269. doi: 10.1093/jac/14.suppl_B.263.
    1. Tsugawa M, Hashimoto H, Monden K, Kumon H, Ohmori H. Antimicrobial prophylaxis in transurethral resection of the prostate. Nihon Hinyokika Gakkai Zasshi. 1998;89(4):453–459.
    1. Hall JC, Christiansen KJ, England P, Low AI, McRae PJ, Mander J, et al. Antibiotic prophylaxis for patients undergoing transurethral resection of the prostate. Urology. 1996;47(6):852–856. doi: 10.1016/S0090-4295(96)00066-0.
    1. Costa FJ. Lomefloxacin prophylaxis in visual laser ablation of the prostate. Urology. 1994;44(6):933–936. doi: 10.1016/S0090-4295(94)80189-4.
    1. Internationaler Prostata Symptomen-Score (IPSS). . Accessed 14 Jan 2019.
    1. ICH Harmonised Tripartite Guideline. Clinical Safety Data Management: Definitions and Standards for Expected Reporting E2A. . Accessed 24 May 2018.
    1. Newcombe RG. Interval estimation for the difference between independent proportions: comparison of eleven methods. Stat Med. 1998;17(8):873–890. doi: 10.1002/(SICI)1097-0258(19980430)17:8<873::AID-SIM779>;2-I.
    1. van Buuren S, Groothuis-Oudshoorn K. Mice: Multivariate Imputation by Chained Equations in R. J Stat Softw. 2011;45(3):1–67. doi: 10.18637/jss.v045.i03.
    1. Woodford N, Ward ME, Kaufmann ME, Turton J, Fagan EJ, James D, et al. Community and hospital spread of Escherichia coli producing CTX-M extended-spectrum beta-lactamases in the UK. J Antimicrob Chemother. 2004;54(4):735–743. doi: 10.1093/jac/dkh424.
    1. Tacconelli E, Carrara E, Savoldi A, Harbarth S, Mendelson M, Monnet DL, Pulcini C, Kahlmeter G, Kluytmans J, Carmeli Y, Ouellette M, Outterson K, Patel J, Cavaleri M, Cox EM, Houchens CR, Grayson ML, Hansen P, Singh N, Theuretzbacher U, Magrini N; WHO Pathogens Priority List Working Group. Discovery, research, and development of new antibiotics: the WHO priority list of antibiotic-resistant bacteria and tuberculosis. Lancet Infect Dis. 2018;18(3):318-27. 10.1016/S1473-3099(17)30753-3.
    1. Bonkat G, Muller G, Braissant O, Frei R, Tschudin-Suter S, Rieken M, et al. Increasing prevalence of ciprofloxacin resistance in extended-spectrum-beta-lactamase-producing Escherichia coli urinary isolates. World J Urol. 2013;31(6):1427–1432. doi: 10.1007/s00345-013-1031-5.
    1. Blaettler L, Mertz D, Frei R, Elzi L, Widmer AF, Battegay M, et al. Secular trend and risk factors for antimicrobial resistance in Escherichia coli isolates in Switzerland 1997-2007. Infection. 2009;37(6):534–539. doi: 10.1007/s15010-009-8457-0.
    1. European Association of Urology (EAU) Urological Infections Guidelines 2018. . Accessed 15 Jan 2019.
    1. Swiss Centre for Antibiotic resistance. . . Accessed 15 Jan 2019.
    1. Centers for Disease Control and Prevention (CDC). Urinary Tract Infection (Catheter-Associated Urinary Tract Infection [CAUTI] and Non-Catheter-Associated Urinary Tract Infection [UTI]) and Other Urinary System Infection [USI]) Events. . Accessed 12 June 2018.

Source: PubMed

Szponzorok és közreműködők

Egészségi állapot

Kábítószer-beavatkozások

3
Iratkozz fel