Duration of Cardiac Antimicrobial Prophylaxis Outcomes Study

Multicentre, Adaptive, Double-blind, Three-arm, Placebo-controlled, Noninferiority Trial Examining Antimicrobial Prophylaxis Duration in Cardiac Surgery

This multicentre, adaptive, pragmatic, double-blind, three-arm, placebo-controlled, randomised, non-inferiority clinical trial will compare the incidence of surgical site infection and other healthcare associated infections, health economic and microbiological impact after intraoperative only (Arm A), to 24 hours (Arm B) and, to 48 hours (Arm C) of IV cefazolin and placebo postoperative surgical antimicrobial prophylaxis in patients undergoing cardiac surgery

This trial will evaluate the clinical effectiveness, health-economic outcomes and microbiological impact of intraoperative (only) compared with intraoperative plus postoperative prophylaxis durations in patients undergoing cardiac surgery.

CALIPSO, a multicentre, adaptive, double-blind, three-arm, placebo-controlled, phase IV, noninferiority trial will examine the incidence proportion of SSI following cardiac surgery. Our three-intervention trial will compare:

Arm A Administration of prophylaxis in intraoperative period only Arm B Administration of prophylaxis in intraoperative plus for 24 hours postoperatively Arm C Administration of prophylaxis in intraoperative plus for 48 hours postoperatively

Inclusion Criteria:

- Adult patients undergoing cardiac surgery involving a median sternotomy

Exclusion Criteria:

• Age <18 years
• American Society of Anesthesiology (ASA) 5
• Subjects with GFR <40mL/min/1.73m2 or those requiring continuous renal replacement therapy, haemodialysis or peritoneal dialysis
• Surgery for suspected or proven endocarditis or deep sternal wound infection
• Documented cefazolin hypersensitivity
• Documented methicillin resistant Staphylococcus aureus (MRSA) colonisation or infection in the 12-months prior to index surgery
• Cardiac transplantation
• Procedures involving insertion ventricular assist device or mechanical circulatory support device
• Procedures not involving a median sternotomy
• Patients previously enrolled and randomised to the CALIPSO trial