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

The goal of this pragmatic, multi-centre factorial cluster randomized cross-over trial is to assess the efficacy of a combination of cefazolin plus vancomycin compared to cefazolin monotherapy, as well as a comparison of short versus long-term prophylaxis with four study arms: 1) cefazolin short-term, 2) cefazolin long-term, 3) cefazolin plus vancomycin short-term and 4) cefazolin plus vancomycin long-term.

Study Overview

• Status: Not yet recruiting
• Conditions: Infection, Surgical Site
• Intervention / Treatment: Drug: Cefazolin; Drug: Vancomycin

Detailed Description

Although antibiotic prophylaxis is considered the cornerstone of prevention for sternal surgical site infections (s-SSIs), the most effective antimicrobial regimen and optimal duration remain unclear. There is a pressing need to determine how best to prevent sternal surgical site infections and at the same time reduce adverse events from unnecessary antibiotic exposure. Currently, due to the lack of evidence, unproven approaches prevail and adherence to guidelines is poor. Rigorous randomized controlled trials data are needed for improved patient care.

A factorial cluster randomized cross-over trial, a design not used previously in this field, will address these gaps. To date, we have successfully enrolled close to 6,000 eligible patients in the vanguard study, and have shown that the trial as planned is feasible and operationally highly cost-effective.

• Study Type: Interventional
• Enrollment (Estimated): 38000
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Dominik Mertz, MD, MSc; Phone Number: 43952 905-521-2100; Email: mertz@hhsc.ca
• Study Contact Backup: Name: Ingrid Copland; Email: pics@phri.ca

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

Adult patients (≥18 years of age) undergoing open-heart surgery (i.e. sternotomy, including minimally-invasive surgical techniques through mini-sternotomies)

Exclusion Criteria:

1. On systemic antibiotics or with an active bacterial infection at the time of surgery
2. Previously enrolled in this trial
3. Known to be colonized with methicillin-resistant staphylococcus aureus (MRSA). Where it is unethical to not administer glycopeptides.
4. Beta-lactam or vancomycin allergy precluding the use of cefazolin or vancomycin, respectively
5. Participation in other studies that may interfere with this trial.
6. Patients undergoing cardiac transplant

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 short-term; Cefazolin 2g (or 3g if greater than 120kg body weight) will be given within an hour of surgery. The intraoperative dose at 4 hours after the first dose or upon wound closure (whatever comes first).	Drug: Cefazolin; administration as outlined; Other Names: Ancef; Kefzol
Experimental: cefazolin long-term; Cefazolin 2g (or 3g if greater than 120kg body weight) will be given within an hour of surgery. The intraoperative dose at 4 hours after the first dose or upon wound closure (whatever comes first) and the five post-operative doses in the long-term arms will be 2g every 8 hours.	Drug: Cefazolin; administration as outlined; Other Names: Ancef; Kefzol
Experimental: cefazolin plus vancomycin short-term; Cefazolin 2g (or 3g if greater than 120kg body weight) will be given within an hour of surgery. The intraoperative dose at 4 hours after the first dose or upon wound closure (whatever comes first). Vancomycin will be dosed at roughly 15mg/kg body weight intravenously, i.e. 1g or 1.5g if greater than 85kg body weight and is to be administered within 60-90 minutes of the surgical procedure.	Drug: Cefazolin; administration as outlined; Other Names: Ancef; Kefzol; Drug: Vancomycin; administered as outlined; Other Names: Firvanq; Vancocin
Experimental: cefazolin plus vancomycin long-term; Cefazolin 2g (or 3g if greater than 120kg body weight) will be given within an hour of surgery. The intraoperative dose at 4 hours after the first dose or upon wound closure (whatever comes first) and the five post-operative doses in the long-term arms will be 2g every 8 hours. Vancomycin will be dosed at roughly 15mg/kg body weight intravenously, i.e. 1g or 1.5g if greater than 85kg body weight and is to be administered within 60-90 minutes of the surgical procedure. The same dose will be used for the 3 post-operative doses in the long-term arm.	Drug: Cefazolin; administration as outlined; Other Names: Ancef; Kefzol; Drug: Vancomycin; administered as outlined; Other Names: Firvanq; Vancocin

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Deep incisional or organ/space (complex) sternal surgical site infection (CDC/NHSN)	Sternal surgical site infections are defined by clinical and microbiological criteria of infection at the surgical site that are associated with the operative procedure occurring within 90 days after surgery.	3 months post-surgery

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
All types of sternal surgical site infections (superficial, deep, organ; (CDC/NHSN)	Sternal surgical site infections are defined by clinical and microbiological criteria of infection at the surgical site that are associated with the operative procedure occurring within 90 days after surgery.	3 months post-surgery
Clostridium difficile infection	Laboratory confirmed	3 months post-surgery
Mortality	Mortality in participants with an active infection	3 months post-surgery
Number of patients with acute kidney injury	Acute kidney injury following the Acute Kidney Injury Network definition	7 days post surgery
Number of patients with sternal revision surgery	For suspected sternal surgical site infection	3 months post surgery
Rate of antimicrobial resistant organisms causing sternal wound infections	including relevant susceptibilities and stratified by study arm	3 months post-surgery

Collaborators and Investigators

• Sponsor: Hamilton Health Sciences Corporation
• Collaborators: Canadian Institutes of Health Research (CIHR)
• Investigators: Principal Investigator: Dominik Mertz, MD, MSc, Hamilton Health Sciences Corporation

Study record dates

Study Major Dates

• Study Start (Estimated): March 1, 2026
• Primary Completion (Estimated): April 30, 2028
• Study Completion (Estimated): July 30, 2028

Study Registration Dates

• First Submitted: August 20, 2024
• First Submitted That Met QC Criteria: August 20, 2024
• First Posted (Actual): August 23, 2024

Study Record Updates

• Last Update Posted (Actual): March 12, 2026
• Last Update Submitted That Met QC Criteria: March 10, 2026
• Last Verified: December 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Postoperative Complications; Pathologic Processes; Infections; Wound Infection; Pathological Conditions, Signs and Symptoms; Surgical Wound Infection; Peptides; Amino Acids, Peptides, and Proteins; Sulfur Compounds; Organic Chemicals; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Carbohydrates; Amides; Glycoconjugates; beta-Lactams; Lactams; Cephalosporins; Thiazines; Glycopeptides; Vancomycin; Cefazolin
• Other Study ID Numbers: PICS

Drug and device information, study documents

• 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