Infection, Surgical Site
Conditions
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.
Interventions
DRUGCefazolin
administration as outlined
DRUGVancomycin
administered as outlined
Sponsors
Hamilton Health Sciences Corporation
Canadian Institutes of Health Research (CIHR)
Study design
Allocation
RANDOMIZED
Intervention model
FACTORIAL
Primary purpose
PREVENTION
Masking
SINGLE (Outcomes Assessor)
Intervention model description
Factorial Assignment
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Deep incisional or organ/space (complex) sternal surgical site infection (CDC/NHSN) | 3 months post-surgery | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| All types of sternal surgical site infections (superficial, deep, organ; (CDC/NHSN) | 3 months post-surgery | 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. |
| Clostridium difficile infection | 3 months post-surgery | Laboratory confirmed |
| Mortality | 3 months post-surgery | Mortality in participants with an active infection |
| Number of patients with acute kidney injury | 7 days post surgery | Acute kidney injury following the Acute Kidney Injury Network definition |
| Number of patients with sternal revision surgery | 3 months post surgery | For suspected sternal surgical site infection |
| Rate of antimicrobial resistant organisms causing sternal wound infections | 3 months post-surgery | including relevant susceptibilities and stratified by study arm |
Contacts
CONTACTDominik Mertz, MD, MSc
CONTACTIngrid Copland
PRINCIPAL_INVESTIGATORDominik Mertz, MD, MSc
Hamilton Health Sciences Corporation
Outcome results
None listed