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)
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)
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经尿道前列腺切除术或绿光激光汽化术中单剂量与 3 天复方新诺明的预防：多中心随机安慰剂对照非劣效性试验的研究方案（CITrUS 试验）
作者：
B. Speich;K. Bausch;Jan A. Roth;L. Hemkens;Hannah Ewald;D. Vogt;Nicole Bruni;S. Deuster;H. Seifert;A. Widmer
背景经尿道前列腺切除术（TURP）和前列腺绿光激光汽化术（GL）是泌尿外科手术中经常进行的手术。对于 TURP，建议单剂量抗菌预防 (AP) 以减少术后尿路感染。迄今为止，尚未为 GL 制定 AP 的国际建议。在瑞士、德国和奥地利进行的一项基于调查的研究中，泌尿科医生报告称，在两次干预后，通常将 AP 主要延长 3 天。因此，我们的目的是确定对于接受前列腺 TURP 或 GL 的患者，单剂量 AP 联合新诺明是否不劣于 3 天 AP 联合新诺明。方法/设计我们将进行一项由研究者发起的、多中心、随机对照试验。我们计划评估单剂量 AP 与 3 天 AP 相比的非劣效性。主要结局是临床诊断的症状性尿路感染的发生情况，并在随机分组后 30 天内使用抗菌药物治疗。绝大多数收集的结果将根据常规收集的数据进行评估。估计样本量能够显示单剂量 AP 与 3 天 AP 相比的非劣效性，在 α = 5% 的显着性水平上至少有 80% 功效 (1 – β = 0.8)，采用 1:1 随机化方案。确定非劣效性界限是为了保留常规护理对主要结局的 70% 的效果。假定两个治疗组的事件发生率为 9%，则非劣效裕度为 4.4%（即 13.4% 至 9%）。为了证明非劣效性，总共应招募1574名患者，以便有1416名可评估患者。该研究得到了瑞士国家科学基金会的支持。讨论对于 TURP 和 GL 中的 AP，通常的临床实践和循证指南之间存在很大差距。如果单剂量 AP 被证明不劣于延长 AP，我们的研究结果可能有助于缩短日常生活中 AP 的持续时间，从而潜在地降低出现与 AP 相关的耐药性和并发症的风险。试验注册Clinicaltrials.gov，NCT03633643。 2018 年 8 月 16 日注册。
BackgroundTransurethral 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/designWe 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.DiscussionFor 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 registrationClinicaltrials.gov, NCT03633643. Registered 16 August 2018.