Prevention of Infections in Cardiac Surgery

Study Overview
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Brief Summary
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There is clinical equipoise about the question of whether antibiotic prophylaxis should be given for a short period or an extended period of time as reflected by inconsistencies in major guidelines, current practices at Canadian centers, and as concluded in the three systematic reviews. There also is clinical equipoise on whether the addition of vancomycin to routine cefazolin prophylaxis can further reduce s-SSI rates. A short duration of combined antimicrobial prophylaxis can reduce side effects of exposure to antimicrobials such as infections with C. difficile or emergence of resistance, but may also reduce the incidence of s-SSIs. The objective of the eventual full scale study is to determine whether adding vancomycin to cefazolin can reduce SSIs as well as whether short-term prophylaxis is as effective as long-term prophylaxis. The rationale to conduct the proposed pilot study is to assess the feasibility to conduct this factorial cluster randomized cross-over trial, the adherence to the study protocol at each pilot site, the length of time to fill out the case report forms, and to get reliable estimates of event rates for sample size calculation for the main study

Official Title
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Prevention of Infections in Cardiac Surgery: a Cluster-randomized Factorial Cross-over Trial

Conditions
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Thoracic Surgery, Antibiotic Prophylaxis

Intervention / Treatment
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* Drug: Cefazolin
* Drug: Vancomycin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: All adult patients (≥18 years of age) undergoing open-heart surgery (sternotomy, including minimally-invasive surgical techniques). Exclusion Criteria: Patients on antibiotics at the time of surgery. Previous enrollment in this trial. Known MRSA carriers. Beta-lactam allergy (IgE-mediated) precluding the use of cefazolin Participant in another study 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: Factorial Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cefazolin monotherapy, short course<br>One pre-op dose of cefazolin 30-60 minutes prior to surgery followed by a second dose either four hours after the first dose or upon wound closure (whatever comes first) will be administered | Drug: Cefazolin<br>* administration as outlined<br>|
| Experimental: Cefazolin monotherapy, long course<br>One pre-op dose of cefazolin 30-60 minutes prior to surgery followed by a second dose either four hours after the first dose or upon wound closure (whatever comes first) will be administered followed by additional five doses every eight hours postoperatively (last dose 44 hours after the first dose). | Drug: Cefazolin<br>* administration as outlined<br>|
| Experimental: Combination therapy, short course<br>One pre-op dose of cefazolin 30-60 minutes prior to surgery followed by a second dose either four hours after the first dose or upon wound closure (whatever comes first) will be administered. In addition, one dose of vancomycin 60-90min pre-op will be administered. | Drug: Cefazolin<br>* administration as outlined<br>Drug: Vancomycin<br>* administration as outlined<br>|
| Experimental: Combination therapy, long course<br>One pre-op dose of cefazolin 30-60 minutes prior to surgery followed by a second dose either four hours after the first dose or upon wound closure (whatever comes first) will be administered followed by additional five doses every eight hours postoperatively (last dose 44 hours after the first dose). In addition, one dose of vancomycin 60-90min pre-op will be administered followed by 3 post-op doses every 12 hours (last dose 36 hours after first dose) | Drug: Cefazolin<br>* administration as outlined<br>Drug: Vancomycin<br>* administration as outlined<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of patients receiving antibiotics according to study protocol | Co-Primary outcome of pilot study | 3 months post-surgery | 
| Proportion of patients with complete follow-up, i.e. up to 90 days or death; goal >95% | Co-Primary outcome of pilot study | 3 months post-surgery | 
| Agreement of blinded outcome assessment based on information from the case report form | Co-Primary outcome of pilot study | 3 months post-surgery | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Deep incisional and organ/space sternal surgical site infection (NHSN/CDC) | Primary outcome of eventual full trial | 3 months post-surgery | 
| All types of sternal surgical site infection (superficial, deep, organ; NHSN/CDC) | Secondary outcome of eventual full trial | 3 months post-surgery | 
| Mortality | Secondary outcome of eventual full trial | 3 months post-surgery | 
| Clostridium difficile infection | Secondary outcome of eventual full trial | 3 months post-surgery |