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

Hamilton Health Sciences (HHS)

Status and phase: Not yet enrolling; Phase 4

Conditions: Infection, Surgical Site

Treatments: Drug: Cefazolin; Drug: Vancomycin

Study type: Interventional

Funder types: Other

Identifiers

NCT06567808

PICS

Details and patient eligibility

About

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.

Full 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.

Enrollment: 38,000 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Prevention

Allocation: Randomized

Interventional model: Factorial Assignment

Masking: Single Blind

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38,000 participants in 4 patient groups

cefazolin short-term

Experimental group

Description:

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).

Treatment:

Drug: Cefazolin

cefazolin long-term

Experimental group

Description:

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.

Treatment:

Drug: Cefazolin

cefazolin plus vancomycin short-term

Experimental group

Description:

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.

Treatment:

Drug: Vancomycin

Drug: Cefazolin

cefazolin plus vancomycin long-term

Experimental group

Description:

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.

Treatment:

Drug: Vancomycin

Drug: Cefazolin