{
  "abstract": "Introduction Administration of antibiotics before incising the skin (‘surgical antimicrobial prophylaxis’) is a critical infection prevention strategy in surgery. Extending doses of prophylaxis into the postoperative period is a common practice in cardiac surgery; however, the benefit has not been clearly established and may lead to emergence of antimicrobial resistance and patient harm. We present the protocol for a large international multicentre, adaptive, pragmatic, double-blind, three-arm, placebo-controlled, randomised, non-inferiority clinical trial to compare the incidence of surgical site infection after three different durations of postoperative surgical antimicrobial prophylaxis in patients undergoing cardiac surgery.Methods and analysis This adaptive, multi-arm multistage non-inferiority trial will compare intraoperative only (Arm A), to intraoperative and 24 hours (Arm B) and, to intraoperative and 48 hours (Arm C) of intravenous cefazolin and placebo as surgical antimicrobial prophylaxis in 9180 patients undergoing cardiac surgery. The adaptive design allows for potential dropping of any of the three arms if clear inferiority is indicated at any of the scheduled interim analyses. The trial will evaluate the clinical and cost-effectiveness of the three different antibiotic prophylaxis durations.Ethics and dissemination Ethics approval will be obtained at all participating sites. Results of the study will be submitted for publication in peer-reviewed journals and the key findings presented at national and international conferences. Patients and members of the public will also be involved in the dissemination and translation of the trial results.Trial registration number NCT05447559.",
  "authors": [
    {
      "affiliations": [
        "Infectious Diseases, Monash University, Melbourne, Victoria, Australia",
        "Infectious Diseases, Alfred Hospital, Melbourne, Victoria, Australia"
      ],
      "name": "Trisha Peel"
    },
    {
      "affiliations": [
        "Cardiothoracic Surgery, Monash University Faculty of Medicine Nursing and Health Sciences, Melbourne, Victoria, Australia",
        "Alfred Hospital, Melbourne, Victoria, Australia"
      ],
      "name": "David McGiffin"
    },
    {
      "affiliations": [
        "Cardiothoracic Surgery, Monash Medical Centre Clayton, Clayton, Victoria, Australia",
        "Department of Surgery, School of Clinical Sciences, Monash University Faculty of Medicine Nursing and Health Sciences, Clayton, Victoria, Australia"
      ],
      "name": "Julian Smith"
    },
    {
      "affiliations": [
        "School of Public Health and Preventative Medicine, Monash University, Melbourne, Victoria, Australia"
      ],
      "name": "Andrew Forbes"
    },
    {
      "affiliations": [
        "Cardiothoracic Surgery, Alfred Hospital, Melbourne, Victoria, Australia"
      ],
      "name": "Silvana Marasco"
    },
    {
      "affiliations": [
        "Australian and New Zealand Intensive Care Society Centre for Outcomes and Resource Evaluation, Melbourne, Victoria, Australia"
      ],
      "name": "David Pilcher"
    },
    {
      "affiliations": [
        "Infectious Diseases, Alfred Hospital, Melbourne, Victoria, Australia",
        "Centre to Impact AMR, Monash University, Melbourne, Victoria, Australia"
      ],
      "name": "Andrew J Stewardson"
    },
    {
      "affiliations": [
        "Centre for Health Economics, Monash University, Melbourne, Victoria, Australia"
      ],
      "name": "Dennis Petrie"
    },
    {
      "affiliations": [
        "Centre to Impact AMR, Monash University, Melbourne, Victoria, Australia",
        "Department of Infectious Diseases, Monash University, Clayton, Victoria, Australia",
        "Infection Program, Monash University Monash Biomedicine Discovery Institute, Clayton, Victoria, Australia"
      ],
      "name": "Anton Y Peleg"
    },
    {
      "affiliations": [
        "Alfred Hospital, Melbourne, Victoria, Australia"
      ],
      "name": "Jessica Wisniewski"
    },
    {
      "affiliations": [
        "Hudson Institute of Medical Research, Clayton, Victoria, Australia"
      ],
      "name": "Samuel Forster"
    },
    {
      "affiliations": [
        "Anaesthesiology and Perioperative Medicine, Monash University, Melbourne, Victoria, Australia",
        "Anaesthesiology and Perioperative Medicine, Alfred Health, Melbourne, Victoria, Australia"
      ],
      "name": "Paige Druce"
    },
    {
      "affiliations": [
        "Infectious Diseases, Alfred Hospital, Melbourne, Victoria, Australia"
      ],
      "name": "Janine Roney"
    },
    {
      "affiliations": [
        "Department of Infectious Diseases, Monash University, Clayton, Victoria, Australia"
      ],
      "name": "Sarah Astbury"
    },
    {
      "affiliations": [
        "Monash University, Clayton, Victoria, Australia"
      ],
      "name": "Danielle Berkovic"
    },
    {
      "affiliations": [
        "Bayside Health, Melbourne, Victoria, Australia",
        "Monash University, Melbourne, Victoria, Australia"
      ],
      "name": "Phoebe Mccracken"
    },
    {
      "affiliations": [
        "Anaesthesiology and Perioperative Medicine, Monash University, Melbourne, Victoria, Australia",
        "Anaesthesiology and Perioperative Medicine, Alfred Hospital, Melbourne, Victoria, Australia"
      ],
      "name": "Paul S Myles"
    },
    {
      "affiliations": [],
      "name": "on behalf of the CALIPSO Trial Steering Committee"
    }
  ],
  "title": "Multicentre, adaptive, double-blind, three-arm, placebo-controlled, non-inferiority trial examining antimicrobial prophylaxis duration in cardiac surgery (CALIPSO): trial protocol",
  "uid": "fb0bc70b-b83e-56a7-90b0-d2b094e9e4cc"
}