Vejlgaard Maja, Stroomberg Hein Vincent, Ynddal Mie Skjøttgaard, Moser Claus, Joensen Ulla Nordström, Røder Andreas
Department of Urology, Centre for Cancer and Organ Diseases, Copenhagen University Hospital - Rigshospitalet, Copenhagen, Denmark.
Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark.
Trials. 2025 Jul 28;26(1):258. doi: 10.1186/s13063-025-08981-w.
In the first months after cystectomy, the most frequent cause of readmission is infection from the urinary tract. Nonetheless, current guidelines are unable to provide evidence-based recommendations on preventative measures and, as a result, antibiotic prophylaxis varies across surgical centres. Most centres in Denmark administer empiric antibiotic prophylaxis at ureteral stent removal after cystectomy, where infection rates peak. However, data indicates that the postoperative urinary microbiota is composed of a wide range of bacteria, suggesting that the patients may benefit from an individualised approach. This trial aims to test whether targeted postoperative antibiotic prophylaxis can reduce infection-related readmissions after cystectomy compared to the current empiric approach.
We present a multicentre, open-label, superiority, randomised clinical trial using a group-sequential design. Participants will be randomly assigned with a 1:1 allocation ratio to receive one of two orally administered single-day antibiotic treatments on the day of ureteral stent removal: (a) standard-of-care pivmecillinam 400 mg morning, noon, and evening or (b) antibiotics targeted to the microbiota identified in a postoperative urine sample. The primary endpoint is the infection-related readmission rate after 90 postoperative days. Secondary endpoints include complication and readmission rates, days alive and out of hospital, quality of life, and microbiological isolates in the urine and blood and antimicrobial susceptibility analyses. A total of 248 patients are planned to be enrolled. The sample size is based on a hypothesised absolute risk reduction in the infection-related readmission rate from 29 to 14%, corresponding to a number needed to treat of six to reduce one hospital readmission. A group-sequential design is proposed to allow for early stopping at interim analysis after 50% enrolment based on predefined rules.
Responsible use of antibiotics is gaining increasing importance globally, and proper prophylactic strategies amongst high-risk patients are essential to avoid hospital admissions with administration of broad-spectrum agents. In this protocol, we present the first randomised clinical trial testing whether individualised targeted antibiotics can reduce the risk of infections after cystectomy. Results of the trial may improve recovery for this vulnerable patient group, while also potentially improving antibiotic stewardship.
EU trial number 2024-514312-27-00. Registered on December 10, 2024.
gov NCT06709196. Registered on November 27, 2024.
在膀胱切除术后的最初几个月里，再次入院最常见的原因是泌尿系统感染。然而，目前的指南无法就预防措施提供基于证据的建议，因此，各手术中心的抗生素预防方案各不相同。丹麦的大多数中心在膀胱切除术后输尿管支架取出时给予经验性抗生素预防，此时感染率最高。然而，数据表明，术后尿液微生物群由多种细菌组成，这表明患者可能受益于个性化方法。本试验旨在测试与目前的经验性方法相比，针对性的术后抗生素预防是否能降低膀胱切除术后与感染相关的再次入院率。
我们采用成组序贯设计进行一项多中心、开放标签、优效性随机临床试验。参与者将按1:1的分配比例随机分组，在输尿管支架取出当天接受两种口服单日抗生素治疗中的一种：（a）标准治疗药物匹美西林400mg，每日早、中、晚各一次；或（b）针对术后尿液样本中鉴定出的微生物群的抗生素。主要终点是术后90天内与感染相关的再次入院率。次要终点包括并发症和再次入院率、存活且出院天数、生活质量以及尿液和血液中的微生物分离株及抗菌药敏分析。计划共招募248名患者。样本量基于假设的与感染相关的再次入院率从29%降至14%的绝对风险降低，即每治疗6例可减少1例再次入院。建议采用成组序贯设计，以便在入组50%后根据预定义规则进行中期分析时提前终止试验。
抗生素的合理使用在全球范围内日益重要，高危患者的适当预防策略对于避免因使用广谱药物而住院至关重要。在本方案中，我们展示了第一项随机临床试验，测试个性化靶向抗生素是否能降低膀胱切除术后的感染风险。试验结果可能改善这一脆弱患者群体的恢复情况，同时也可能改善抗生素管理。
欧盟试验编号2024 - 514312 - 27 - 00。于2024年12月10日注册。
ClinicalTrials.gov标识符：NCT06709196。于2024年11月27日注册。
