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

NCT ID: NCT06567808

Last Updated: 2025-06-13

Basic Information

• Recruitment Status: NOT_YET_RECRUITING
• Clinical Phase: PHASE4
• Total Enrollment: 38000 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2025-08-01
• Study Completion Date: 2028-07-30

Brief Summary

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.

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.

Conditions

Infection, Surgical Site

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: FACTORIAL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: SINGLE

Study Groups

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).

Group Type: EXPERIMENTAL

Cefazolin

Intervention Type: DRUG

administration as outlined

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.

Group Type: EXPERIMENTAL

Cefazolin

Intervention Type: DRUG

administration as outlined

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.

Group Type: EXPERIMENTAL

Cefazolin

Intervention Type: DRUG

administration as outlined

Vancomycin

Intervention Type: DRUG

administered as outlined

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.

Group Type: EXPERIMENTAL

Cefazolin

Intervention Type: DRUG

administration as outlined

Vancomycin

Intervention Type: DRUG

administered as outlined

Interventions

Cefazolin

administration as outlined

Intervention Type: DRUG

Vancomycin

administered as outlined

Intervention Type: DRUG

Other Intervention Names

Kefzol; Ancef; Vancocin; Firvanq

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Canadian Institutes of Health Research (CIHR)

OTHER_GOV

Sponsor Role: collaborator

Hamilton Health Sciences Corporation

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Dominik Mertz, MD, MSc

Role: PRINCIPAL_INVESTIGATOR

Hamilton Health Sciences Corporation

Central Contacts

Dominik Mertz, MD, MSc

Role: CONTACT

mertz@hhsc.ca

905-521-2100 ext. 43952

Ingrid Copland

Role: CONTACT

pics@phri.ca

Other Identifiers

PICS

Identifier Type: -

Identifier Source: org_study_id