Prevention of Infections in Cardiac Surgery (PICS) Prevena Study

Study Overview
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Brief Summary
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This vanguard study will be conducted at two study sites in Canada. It is a cluster randomized trial to test a combination of two antibiotics for antibiotic prophylaxis as compared to routine prophylaxis with one single antibiotic, and to test a negative-pressure wound management system (Prevena) versus standard wound dressing to reduce chest wound infections.

Detailed Description
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Despite the routine use of antibiotics before and after cardiac surgery, infections of the chest wound remain a common life threatening complication of heart surgery that is preventable. Antibiotic prophylaxis is well accepted to be the cornerstone of prevention for these infections. The best choice of antibiotic prophylaxis in patients undergoing open heart surgery is, however, unclear. A large number of relevant pathogens are not covered by the primarily recommended antibiotic for prophylaxis, and there is a large variability in the antibiotics physicians use in practice and a lack of evidence supporting these choices. Appropriate management of the wound is probably also highly relevant in terms of infection prevention; however, there is a lack of strong evidence guiding the choice of wound management strategies as a means to reduce surgical site infection. The proposed study will test whether dual antibiotic prophylaxis is superior to single-agent prophylaxis with cefazolin, and shed light on whether or not modern negative-pressure wound management technology lower the risk of sternal surgical site infections.

Official Title
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A Cluster-randomized Factorial Crossover Trial, Comparing Antibiotic Mono-prophylaxis With Cefazolin vs. Dual-prophylaxis With Cefazolin Plus Vancomycin and Conventional Wound Dressing vs. Prevena Negative-pressure Wound Management

Conditions
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Surgical Site Infections

Intervention / Treatment
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* Device: Prevena
* Drug: Cefazolin
* Drug: Vancomycin
* Other: standard wound dressing


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: - ≥18 years of age undergoing open-heart surgery (sternotomy, including minimally-invasive sternotomies) Exclusion Criteria: On systemic antibiotics or with an active bacterial infection at the time of surgery Patients previously enrolled in this trial Patients known to be colonized with Methicillin-resistant S. aureus (MRSA)(unethical not to administer glycopeptides), beta-lactam or vancomycin allergy precluding the use of cefazolin or vancomycin, respectively, or to silver precluding the use of Prevena Participation in other studies that may interfere with this trial

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Crossover Assignment
Interventional Model Description: 1) cefazolin prophylaxis plus Prevena*(*diabetic and/or obese patients (BMI >30kg/m2)) 2) cefazolin and vancomycin prophylaxis plus Prevena*(*diabetic and/or obese patients (BMI >30kg/m2)), 3) cefazolin prophylaxis plus standard wound dressing, 4) cefazolin and vancomycin prophylaxis plus standard wound dressing.
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Arm 1<br>cefazolin prophylaxis plus Prevena negative-pressure wound management system . Cefazolin 2g (or 3g if greater than 120kg body weight) will be given within an hour of surgery, followed by one intra-operative dose of cefazolin at 4 hours after the first dose or upon wound closure (whatever comes first), and finally two post-operative doses q8h. Prevena will be applied to all diabetic and/or obese patients (BMI >30kg/m2) at the end of surgery on the sternal as well as the vein harvest site (if open saphenous vein harvest) in the OR and left in place for 7 day | Device: Prevena<br>* Negative-Pressure Wound Management System<br>Drug: Cefazolin<br>* antibiotic<br>|
| Active Comparator: Arm 2<br>cefazolin and vancomycin prophylaxis plus Prevena negative-pressure wound management system. Cefazolin 2g (or 3g if greater than 120kg body weight) within an hour of surgery, followed by one intra-operative dose of cefazolin at 4 hrs after the first dose or upon wound closure (whatever comes first), and finally two post-operative doses q8h. Vancomycin at roughly 15mg/kg body weight intravenously, i.e. 1g, or 1.5g if greater than 85kg body weight. No intra-operative dose of vancomycin will be given, and a single second dose will be given 12 hours after the first dose. Prevena will be applied to all diabetic and/or obese patients (BMI >30kg/m2) at the end of surgery on the sternal as well as the vein harvest site (if open saphenous vein harvest) in the OR and left in place for 7 days. | Device: Prevena<br>* Negative-Pressure Wound Management System<br>Drug: Cefazolin<br>* antibiotic<br>Drug: Vancomycin<br>* antibiotic<br>* Other names: Vancocin;|
| Active Comparator: Arm 3<br>cefazolin prophylaxis plus standard wound dressing. Cefazolin 2g (or 3g if greater than 120kg body weight) within an hour of surgery, followed by one intra-operative dose of cefazolin at 4 hours after the first dose or upon wound closure (whatever comes first), and finally two post-operative doses q8h. Standard wound dressing: non-negative wound dressing as standard of care at the study site. | Drug: Cefazolin<br>* antibiotic<br>Other: standard wound dressing<br>* Any non-negative pressure wound dressing that is routinely used at study sites will be considered standard of care in the control arms.<br>|
| Active Comparator: Arm 4<br>cefazolin and vancomycin prophylaxis plus standard wound dressing. Cefazolin 2g (or 3g if greater than 120kg body weight) within an hour of surgery, followed by one intra-operative dose of cefazolin at 4 hours after the first dose or upon wound closure (whatever comes first), and finally two post-operative doses q8h. Vancomycin at roughly 15mg/kg body weight intravenously, i.e. 1g, or 1.5g if greater than 85kg body weight. No intra-operative dose of vancomycin will be given, and a single second dose will be given 12 hours after the first dose. Standard wound dressing: non-negative wound dressing as standard of care at the study site. | Drug: Cefazolin<br>* antibiotic<br>Drug: Vancomycin<br>* antibiotic<br>* Other names: Vancocin;Other: standard wound dressing<br>* Any non-negative pressure wound dressing that is routinely used at study sites will be considered standard of care in the control arms.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Adherence to the wound management system | goal is >90% | Prevena or standard wound dressing applied after surgery as per protocol, assessed up to 90 days after surgery | 
| Adherence to the antibiotic regimen | goal is >90% | Cefazolin: within an hour of surgery; one intra-operative dose at 4 hours after the first dose or upon wound closure (whatever comes first); two post-operative doses q8h. Vancomycin: initially intravenously; second dose 12 hrs after the first dose. | 
| Loss of follow-up | goal is <10% | up to 90 days after surgery | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Deep incisional and organ/space sternal-surgical site infection (s-SSI) | using standardized CDC/NHSN (Centre for Disease Control and Prevention/National Healthcare Safety Network) definitions | up to 90 days after surgery | 
| Wound dehiscence | using standardized CDC/NHSN (Centre for Disease Control and Prevention/National Healthcare Safety Network) definitions | up to 90 days after surgery | 
| C. difficile infection | laboratory confirmed | up to 90 days after surgery | 
| Mortality in patients with an active infection | using standardized CDC/NHSN (Centre for Disease Control and Prevention/National Healthcare Safety Network) definitions | up to 90 days after surgery | 
| ICU (Intensive Care Unit) and hospital stay | length | Length of ICU - from date of surgery to initial ICU discharge date, assessed up to 90 days after surgery. Hospital Stay - date of surgery to date of hospital discharge, assessed up to 90 days after surgery. | 
| Pain on day 7 | Visual analog scale (VAS) | Pain at Day 7 (+/- 1 day) | 
| Acute kidney injury | Based on serum creatinine, following Acute Kidney Injury Network definition | within 7 days of surgery | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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negative pressure wound management system, open-heart surgery, antibiotic prophylaxis, surgical site infection