CALIPSO: Duration of Cardiac Antimicrobial Prophylaxis Outcomes Study

• Sponsor: Monash University (Other)
• Overall Status: Not yet recruiting
• CT.gov ID: NCT05447559
• Collaborator: The Alfred (Other)
• Enrollment: 9,000
• Arms: 3
• Anticipated Duration (Months): 57

Study Details

Study Description

Brief Summary

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

Condition or Disease	Intervention/Treatment	Phase
Surgical Site Infection	Drug: Cefazolin; Drug: Water for injection	Phase 4

Detailed Description

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

Study Design

• Study Type: Interventional
• Anticipated Enrollment: 9000 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Intervention Model Description: Adaptive, double-blind, three-arm, placebo-controlled, phase IV, noninferiority trialAdaptive, double-blind, three-arm, placebo-controlled, phase IV, noninferiority trial
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Masking Description: Participants, treating clinicians, all members of the research team including the study statistician will be blinded to treatment arm allocation. Active treatment will consist of 2-grams cefazolin powder for injection. Placebo will consist of an identical empty vial. The commercial labels will be removed and a sheath placed over the vial. Amber-tinted syringes will be provided for drawing up and administration of cefazolin/placebo to mask study arm. The vial containing cefazolin or placebo will be reconstituted in a minimum of 10 mL of sterile water for injections and administered in keeping with product information for cefazolin and / or local guidelines.
• Primary Purpose: Prevention
• Official Title: Multicentre, Adaptive, Double-blind, Three-arm, Placebo-controlled, Noninferiority Trial Examining Antimicrobial Prophylaxis Duration in Cardiac Surgery
• Anticipated Study Start Date: Sep 1, 2022
• Anticipated Primary Completion Date: Jan 1, 2027
• Anticipated Study Completion Date: Jun 1, 2027

Arms and Interventions

Arm	Intervention/Treatment
Placebo Comparator: Intraoperative only Surgical Antimicrobial Prophylaxis Arm Placebo administered every 8-hours following the preoperative dose (time=0) for a total of five postoperative doses	Drug: Water for injection; Intravenous administration of 10mL sterile water for injection
Other: Intraoperative and 24-hours Postoperative Surgical Antimicrobial Prophylaxis Arm 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; Intravenous administration of 2 g cefazolin; Drug: Water for injection; Intravenous administration of 10mL sterile water for injection
Active Comparator: Intraoperative and 48-hours Postoperative Surgical Antimicrobial Prophylaxis Arm Cefazolin (2g) administered every 8-hours following the preoperative dose (time=0) for a total of five postoperative doses	Drug: Cefazolin; Intravenous administration of 2 g cefazolin

Outcome Measures

Primary Outcome Measures

1. Incidence of surgical site infection [90 days from index surgery]

   Surgical site infection according to CDC / NHSN definition

Secondary Outcome Measures

1. Incidence of Clostridioides difficile infection [30 days from index surgery]

   Clostridioides difficile infection according the CDC definitions

2. Incidence of other health care association infections [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]

   Composite of all other HCAIs (pneumonia, blood stream infection and urinary tract infection)

Other Outcome Measures

1. Incidence of Antimicrobial hypersensitivity reactions [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]

   Immediate (<48 hrs after exposure) or delayed (≥24 hrs after exposure) reaction to study drug

2. All-cause mortality rate [180 days from index surgery]

   Death reported up to 180 days from index cardiac surgery due to any cause.

3. Incidence of acute kidney injury [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]

   AKI will be defined according to the RIFLE criteria

4. Incidence of surgical site infections due to drug-resistant infections [90 days from index surgery]

   Surgical site infections due to drug-resistant infections (defined as resistance to cefazolin)

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

No locations specified.

Sponsors and Collaborators

• Monash University
• The Alfred

Investigators

• Principal Investigator: Trisha Peel, MBBS GradCertRes FRACP PhD, Monash University

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Trisha Nicole Peel, Associate Professor Trisha Peel, Monash University
• ClinicalTrials.gov Identifier: NCT05447559
• Other Study ID Numbers: 228/22
• First Posted: Jul 7, 2022
• Last Update Posted: Jul 7, 2022
• Last Verified: Jul 1, 2022

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: No
• Keywords provided by Trisha Nicole Peel, Associate Professor Trisha Peel, Monash University: Cardiac surgery
• Additional relevant MeSH terms: Surgical Wound Infection; Cefazolin

Study Results

No Results Posted as of Jul 7, 2022