van Oostveen Rachel B, Romero-Palacios Alberto, Whitlock Richard, Lee Shun Fu, Connolly Stuart, Carignan Alex, Mazer C David, Loeb Mark, Mertz Dominik
Population Health Research Institute (PHRI), Hamilton Health Sciences, Hamilton, ON, Canada.
McMaster University, Hamilton, ON, Canada.
Trials. 2018 Dec 17;19(1):688. doi: 10.1186/s13063-018-3080-y.
A wide range of prophylactic antibiotic regimens are used for patients undergoing open-heart cardiac surgery. This reflects clinical equipoise in choice and duration of antibiotic agents. Although individual-level randomized control trials (RCT) are considered the gold standard when evaluating the efficacy of an intervention, this approach is highly resource intensive and a cluster RCT can be more appropriate for testing clinical effectiveness in a real-world setting.
METHODS/DESIGN: We are conducting a factorial cluster-randomized crossover pilot trial in cardiac surgery patients to evaluate the feasibility of this design for a definite trial to evaluate the optimal duration and choice of perioperative antibiotic prophylaxis. Specifically, we will evaluate: (a) the non-inferiority of a single preoperative dose compared to prolonged prophylaxis and (b) the potential superiority of adding vancomycin to routine cefazolin in terms of preventing deep and organ/space sternal surgical site infections (s-SSIs). There are four strategies: (i) short-term cefazolin, (ii) long-term cefazolin, (iii) short-term cefazolin + vancomycin, and (iv) long-term cefazolin + vancomycin. These strategies are delivered in a different order in each health-care center participating in the trial. The centers are randomized to an order, and the current strategy becomes the standard operating procedure in that center during the study. The three feasibility outcomes include: (1) the proportion of patients receiving preoperative, intra-operative, and postoperative antibiotics according to the study protocol, (2) the proportion of completed follow-up assessments, and (3) a full and final assessment of the incidence of s-SSIs by the outcome adjudication committee.
We believe that a cluster-randomized factorial crossover trial is an effective and feasible design for these research questions, allowing an evaluation of the clinical effectiveness in a real-world setting. A waiver of individual informed consent was considered appropriate by the research ethics boards in each participating site in Canada as long as an information letter with an opt-out option was provided. However, a waiver of consent was not approved at two sites in Germany and Switzerland, respectively.
Clinicaltrials.gov, NCT02285140 . Registered on 15 October 2015.
心脏直视手术患者会使用多种预防性抗生素方案。这反映出在抗生素的选择和使用时长方面存在临床权衡。虽然个体层面的随机对照试验（RCT）在评估干预措施的疗效时被视为金标准，但这种方法资源消耗极大，而整群随机对照试验可能更适合在现实环境中测试临床有效性。
方法/设计：我们正在对心脏手术患者开展一项析因整群随机交叉试点试验，以评估这种设计用于确定试验的可行性，该试验旨在评估围手术期抗生素预防的最佳时长和选择。具体而言，我们将评估：（a）单次术前剂量与延长预防相比的非劣效性，以及（b）在预防深部和器官/间隙胸骨手术部位感染（s-SSIs）方面，在常规头孢唑林中添加万古霉素的潜在优越性。有四种策略：（i）短期头孢唑林，（ii）长期头孢唑林，（iii）短期头孢唑林+万古霉素，以及（iv）长期头孢唑林+万古霉素。在参与试验的每个医疗中心，这些策略以不同顺序实施。各中心被随机分配一种顺序，在研究期间，当前策略成为该中心的标准操作程序。三项可行性结果包括：（1）按照研究方案接受术前、术中和术后抗生素治疗的患者比例，（2）完成随访评估的比例，以及（3）结局判定委员会对s-SSIs发生率的全面最终评估。
我们认为，整群随机析因交叉试验对于这些研究问题是一种有效且可行的设计，能够在现实环境中评估临床有效性。加拿大各参与站点的研究伦理委员会认为，只要提供带有退出选项的信息函，放弃个体知情同意是合适的。然而，在德国和瑞士的两个站点，分别未获批放弃同意。
Clinicaltrials.gov，NCT02285140。于2015年10月15日注册。
