Prevention of Infections in Cardiac Surgery (PICS) Prevena Study (PICS-Prevena)

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

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Surgical Site Infections
• Intervention / Treatment: Device: Prevena; Drug: Cefazolin; Drug: Vancomycin; Other: standard wound dressing

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 4107
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Ingrid Copland, CCRA; Phone Number: 40368 905-527-4322; Email: prevena@phri.ca

Study Locations

• Canada
  • Ontario
    • Hamilton, Ontario, Canada, L8L 2X2
      • Hamilton General Hospital
    • London, Ontario, Canada, N6A 5A5
      • London Health Sciences Centre & Lawson Health Research Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Single

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Arm 1; 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; Negative-Pressure Wound Management System; Drug: Cefazolin; antibiotic
Active Comparator: Arm 2; 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; Negative-Pressure Wound Management System; Drug: Cefazolin; antibiotic; Drug: Vancomycin; antibiotic; Other Names: Vancocin
Active Comparator: Arm 3; 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; antibiotic; Other: standard wound dressing; Any non-negative pressure wound dressing that is routinely used at study sites will be considered standard of care in the control arms.
Active Comparator: Arm 4; 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; antibiotic; Drug: Vancomycin; antibiotic; Other Names: Vancocin; Other: standard wound dressing; Any non-negative pressure wound dressing that is routinely used at study sites will be considered standard of care in the control arms.

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Population Health Research Institute
• Investigators: Principal Investigator: Dominik Mertz, MD,MSc, Juravinski Hospital and Cancer Centre

Publications and helpful links

General Publications

• Edwards FH, Engelman RM, Houck P, Shahian DM, Bridges CR; Society of Thoracic Surgeons. The Society of Thoracic Surgeons Practice Guideline Series: Antibiotic Prophylaxis in Cardiac Surgery, Part I: Duration. Ann Thorac Surg. 2006 Jan;81(1):397-404. doi: 10.1016/j.athoracsur.2005.06.034. No abstract available.
• Connolly SJ, Philippon F, Longtin Y, Casanova A, Birnie DH, Exner DV, Dorian P, Prakash R, Alings M, Krahn AD. Randomized cluster crossover trials for reliable, efficient, comparative effectiveness testing: design of the Prevention of Arrhythmia Device Infection Trial (PADIT). Can J Cardiol. 2013 Jun;29(6):652-8. doi: 10.1016/j.cjca.2013.01.020. Erratum In: Can J Cardiol. 2013 Jul;29(7):889.
• Mertz D, Whitlock R, Kokoszka AY, Smith SW, Carignan A, Rehan M, Jaffer IH, Alsagheir A, Loeb M. Routine Surveillance Versus Independent Assessment by an Outcome Adjudication Committee in Assessing Patients for Sternal Surgical Site Infections After Cardiac Surgery. Infect Control Hosp Epidemiol. 2016 May;37(5):600-2. doi: 10.1017/ice.2015.347. Epub 2016 Jan 19.
• Filsoufi F, Castillo JG, Rahmanian PB, Broumand SR, Silvay G, Carpentier A, Adams DH. Epidemiology of deep sternal wound infection in cardiac surgery. J Cardiothorac Vasc Anesth. 2009 Aug;23(4):488-94. doi: 10.1053/j.jvca.2009.02.007. Epub 2009 Apr 19.
• Lador A, Nasir H, Mansur N, Sharoni E, Biderman P, Leibovici L, Paul M. Antibiotic prophylaxis in cardiac surgery: systematic review and meta-analysis. J Antimicrob Chemother. 2012 Mar;67(3):541-50. doi: 10.1093/jac/dkr470. Epub 2011 Nov 13.
• Mertz D, Johnstone J, Loeb M. Does duration of perioperative antibiotic prophylaxis matter in cardiac surgery? A systematic review and meta-analysis. Ann Surg. 2011 Jul;254(1):48-54. doi: 10.1097/SLA.0b013e318214b7e4.

Study record dates

Study Major Dates

• Study Start (Actual): March 5, 2018
• Primary Completion (Actual): April 27, 2023
• Study Completion (Estimated): June 1, 2024

Study Registration Dates

• First Submitted: January 8, 2018
• First Submitted That Met QC Criteria: January 17, 2018
• First Posted (Actual): January 18, 2018

Study Record Updates

• Last Update Posted (Actual): April 3, 2024
• Last Update Submitted That Met QC Criteria: April 2, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Keywords: surgical site infection; antibiotic prophylaxis; open-heart surgery; negative pressure wound management system
• Additional Relevant MeSH Terms: Pathologic Processes; Postoperative Complications; Wound Infection; Infections; Surgical Wound Infection; Anti-Infective Agents; Anti-Bacterial Agents; Vancomycin; Cefazolin
• Other Study ID Numbers: PICS-PREVENA V1_20171106

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No