Prevention of Infections in Cardiac Surgery (PICS)

Prevention of Infections in Cardiac Surgery: a Cluster-randomized Factorial Cross-over Trial

There is clinical equipoise about the question of whether antibiotic prophylaxis should be given for a short period or an extended period of time as reflected by inconsistencies in major guidelines, current practices at Canadian centers, and as concluded in the three systematic reviews. There also is clinical equipoise on whether the addition of vancomycin to routine cefazolin prophylaxis can further reduce s-SSI rates. A short duration of combined antimicrobial prophylaxis can reduce side effects of exposure to antimicrobials such as infections with C. difficile or emergence of resistance, but may also reduce the incidence of s-SSIs. The objective of the eventual full scale study is to determine whether adding vancomycin to cefazolin can reduce SSIs as well as whether short-term prophylaxis is as effective as long-term prophylaxis. The rationale to conduct the proposed pilot study is to assess the feasibility to conduct this factorial cluster randomized cross-over trial, the adherence to the study protocol at each pilot site, the length of time to fill out the case report forms, and to get reliable estimates of event rates for sample size calculation for the main study

Study Overview

• Status: Active, not recruiting
• Conditions: Thoracic Surgery; Antibiotic Prophylaxis
• Intervention / Treatment: Drug: Cefazolin; Drug: Vancomycin

• Study Type: Interventional
• Enrollment (Estimated): 3000
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Dominik Mertz, MD, MSc; Phone Number: 43952 (905) 521-2100; Email: mertzd@mcmaster.ca
• Study Contact Backup: Name: Richard P Whitlock, MD, PhD; Phone Number: 44091 905 527 4322; Email: richard.whitlock@phri.ca

Study Locations

• Canada
  • Ontario
    • Hamilton, Ontario, Canada, L8L 2X2
      • Hamilton Health Sciences
    • Toronto, Ontario, Canada, M5B1W8
      • St. Michael's Hospital
  • Quebec
    • Montréal, Quebec, Canada, H3T 1E2
      • Jewish Hospital
    • Sherbrook, Quebec, Canada, J1H 5N4
      • University of Sherbrook

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• All adult patients (≥18 years of age) undergoing open-heart surgery (sternotomy, including minimally-invasive surgical techniques).

Exclusion Criteria:

• Patients on antibiotics at the time of surgery.
• Previous enrollment in this trial.
• Known MRSA carriers. Beta-lactam allergy (IgE-mediated) precluding the use of cefazolin
• Participant in another study that may interfere with this trial.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Factorial Assignment
• Masking: Single

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cefazolin monotherapy, short course; One pre-op dose of cefazolin 30-60 minutes prior to surgery followed by a second dose either four hours after the first dose or upon wound closure (whatever comes first) will be administered	Drug: Cefazolin; administration as outlined
Experimental: Cefazolin monotherapy, long course; One pre-op dose of cefazolin 30-60 minutes prior to surgery followed by a second dose either four hours after the first dose or upon wound closure (whatever comes first) will be administered followed by additional five doses every eight hours postoperatively (last dose 44 hours after the first dose).	Drug: Cefazolin; administration as outlined
Experimental: Combination therapy, short course; One pre-op dose of cefazolin 30-60 minutes prior to surgery followed by a second dose either four hours after the first dose or upon wound closure (whatever comes first) will be administered. In addition, one dose of vancomycin 60-90min pre-op will be administered.	Drug: Cefazolin; administration as outlined; Drug: Vancomycin; administration as outlined
Experimental: Combination therapy, long course; One pre-op dose of cefazolin 30-60 minutes prior to surgery followed by a second dose either four hours after the first dose or upon wound closure (whatever comes first) will be administered followed by additional five doses every eight hours postoperatively (last dose 44 hours after the first dose). In addition, one dose of vancomycin 60-90min pre-op will be administered followed by 3 post-op doses every 12 hours (last dose 36 hours after first dose)	Drug: Cefazolin; administration as outlined; Drug: Vancomycin; administration as outlined

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of patients receiving antibiotics according to study protocol	Co-Primary outcome of pilot study	3 months post-surgery
Proportion of patients with complete follow-up, i.e. up to 90 days or death; goal >95%	Co-Primary outcome of pilot study	3 months post-surgery
Agreement of blinded outcome assessment based on information from the case report form	Co-Primary outcome of pilot study	3 months post-surgery

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Deep incisional and organ/space sternal surgical site infection (NHSN/CDC)	Primary outcome of eventual full trial	3 months post-surgery
All types of sternal surgical site infection (superficial, deep, organ; NHSN/CDC)	Secondary outcome of eventual full trial	3 months post-surgery
Mortality	Secondary outcome of eventual full trial	3 months post-surgery
Clostridium difficile infection	Secondary outcome of eventual full trial	3 months post-surgery

Collaborators and Investigators

• Sponsor: Hamilton Health Sciences Corporation
• Collaborators: The Physicians' Services Incorporated Foundation
• Investigators: Principal Investigator: Dominik Mertz, MD, MSc, Hamilton Health Sciences Corporation

Publications and helpful links

General Publications

• van Oostveen RB, Romero-Palacios A, Whitlock R, Lee SF, Connolly S, Carignan A, Mazer CD, Loeb M, Mertz D. Prevention of Infections in Cardiac Surgery study (PICS): study protocol for a pragmatic cluster-randomized factorial crossover pilot trial. Trials. 2018 Dec 17;19(1):688. doi: 10.1186/s13063-018-3080-y. Erratum In: Trials. 2019 Oct 16;20(1):595.

Study record dates

Study Major Dates

• Study Start: April 1, 2015
• Primary Completion (Estimated): August 7, 2026
• Study Completion (Estimated): November 7, 2026

Study Registration Dates

• First Submitted: November 4, 2014
• First Submitted That Met QC Criteria: November 4, 2014
• First Posted (Estimated): November 6, 2014

Study Record Updates

• Last Update Posted (Actual): September 22, 2023
• Last Update Submitted That Met QC Criteria: September 20, 2023
• Last Verified: September 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Infections; Anti-Infective Agents; Anti-Bacterial Agents; Vancomycin; Cefazolin
• Other Study ID Numbers: PICS