Prevention of Infections in Cardiac Surgery study (PICS): study protocol for a pragmatic cluster-randomized factorial crossover pilot trial

Abstract

Background: 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.

Discussion: 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.

Trial registration: Clinicaltrials.gov, NCT02285140 . Registered on 15 October 2015.

Keywords: antibiotic prophylaxis; cardiac surgery; cluster crossover trial.

Conflict of interest statement

Ethics approval and consent to participate

Ethics approval was granted by the principal investigator’s research ethics board for Hamilton Health Sciences, Hamilton, ON (REB#15–129) and was subsequently approved by the local research ethic boards at the two other study sites (Sherbrooke University, Sherbrooke, QC, and St. Michael’s Hospital, Toronto, ON).

Competing interests

The authors declare that they have no competing interests.

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Figures

Fig. 1

SPIRIT figure. *t1-t4: four study arms, order of the study arms for each study site allocated at timepoint ‘0’. **Exclusion criteria applied upon data collection. ***Data collection at least 90 days after surgery