Clinical trial NCT03402945: Prevention of Infections in Cardiac Surgery (PICS) Prevena Study
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Surgical Site Infections
Keywords: negative pressure wound management system
open-heart surgery
antibiotic prophylaxis
surgical site infection
Lead sponsor: Population Health Research Institute
Sponsor class: OTHER
First posted: 2018-01-18
Enrollment: 4107
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Intervention 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.
Primary purpose: PREVENTION

Brief summary: 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: 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.

Eligibility criteria: 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

Primary outcomes:
measure: Adherence to the wound management system
timeFrame: Prevena or standard wound dressing applied after surgery as per protocol, assessed up to 90 days after surgery
measure: Adherence to the antibiotic regimen
timeFrame: 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.
measure: Loss of follow-up
timeFrame: up to 90 days after surgery
Secondary outcomes:
measure: Deep incisional and organ/space sternal-surgical site infection (s-SSI)
timeFrame: up to 90 days after surgery
measure: Wound dehiscence
timeFrame: up to 90 days after surgery
measure: C. difficile infection
timeFrame: up to 90 days after surgery
measure: Mortality in patients with an active infection
timeFrame: up to 90 days after surgery
measure: ICU (Intensive Care Unit) and hospital stay
timeFrame: 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.
measure: Pain on day 7
timeFrame: Pain at Day 7 (+/- 1 day)
measure: Acute kidney injury
timeFrame: within 7 days of surgery
Other outcomes:
Locations:
city: Hamilton
country: Canada
facility: Hamilton General Hospital
state: Ontario
city: London
country: Canada
facility: London Health Sciences Centre & Lawson Health Research Institute
state: Ontario
Study officials:
affiliation: Juravinski Hospital and Cancer Centre
name: Dominik Mertz, MD,MSc
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.