Duration of Cardiac Antimicrobial Prophylaxis Outcomes Study

Study Overview
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Brief Summary
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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

Detailed Description
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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

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

Conditions
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Surgical Site Infection

Intervention / Treatment
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* Drug: Cefazolin
* Drug: Water for injection


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Adaptive, double-blind, three-arm, placebo-controlled, phase IV, noninferiority trial
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Intraoperative only Surgical Antimicrobial Prophylaxis Arm<br>Placebo administered every 8-hours following the preoperative dose (time=0) for a total of five postoperative doses | Drug: Water for injection<br>* Intravenous administration of 10mL sterile water for injection<br>|
| Other: Intraoperative and 24-hours Postoperative Surgical Antimicrobial Prophylaxis Arm<br>Cefazolin (2g) administered 8-hourly following the preoperative dose (time=0) for two doses then placebo 8-hourly for three doses (total of 5 postoperative doses of cefazolin/placebo) | Drug: Cefazolin<br>* Intravenous administration of 2 g cefazolin<br>Drug: Water for injection<br>* Intravenous administration of 10mL sterile water for injection<br>|
| Active Comparator: Intraoperative and 48-hours Postoperative Surgical Antimicrobial Prophylaxis Arm<br>Cefazolin (2g) administered every 8-hours following the preoperative dose (time=0) for a total of five postoperative doses | Drug: Cefazolin<br>* Intravenous administration of 2 g cefazolin<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of surgical site infection | Surgical site infection according to CDC / NHSN definition | 90 days from index surgery | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of Clostridioides difficile infection | Clostridioides difficile infection according the CDC definitions | 30 days from index surgery | 
| Incidence of other health care association infections | Composite of all other HCAIs (pneumonia, blood stream infection and urinary tract infection) | From date of randomization until the date of discharge from the acute healthcare facility or date of death from any cause, whichever came first, assessed up to 30 days from index surgery | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Cardiac surgery