Evaluation of the Potential Impact of Computerized Antimicrobial Stewardship

Study Overview
=================
Brief Summary
-----------------
This trial is an open-label, two-arm, cluster-randomized, controlled trial with cardiovascular surgical teams as the unit of randomization. Eligible teams with written consent are randomized to the intervention or control arm by random number generator. Computer-based, multicomponent intervention targeting on reduction of perioperative antimicrobial use will be delivered to teams in the intervention arm. Teams in the control arm will continue with usual clinical care.

Detailed Description
-----------------
The aim of the EPIC trial is to assess if a multicomponent computer-based system incorporated into the workflow can reduce days of therapy (DOT) per admission after cardiovascular surgeries in the intervention surgical teams compared with controlled surgical teams, over a one-year period. This trial is an open-label, two-arm, cluster-randomized, controlled trial with cardiovascular surgical teams as the unit of randomization. Eligible teams with written consent are randomized to the intervention or control arm by random number generator. Computer-based, multicomponent intervention targeting on reduction of perioperative antimicrobial use will be delivered to teams in the intervention arm. Teams in the control arm will continue with usual clinical care. The intervention includes re-evaluation alerts and decision support for the duration of antimicrobial treatment, re-evaluation alerts and decision support for the choice of antimicrobial, and quality control audit and feedback. Nine teams per arm with an average size of 1125 admissions will be recruited. Primary outcome will be the overall systemic antibiotic use measured in DOT of systemic antibiotic use per admission. Secondary outcomes include a series of indices to evaluate antimicrobial use, microbial resistance, perioperative infection outcomes, patient safety, resource consumption and user compliance/satisfaction.

Official Title
-----------------
Evaluation of the Potential Impact of Computerized Antimicrobial Stewardship on the Antimicrobial Use After Cardiovascular Surgeries

Conditions
-----------------
Antimicrobial Stewardship, Cardiovascular Surgeries, Computerized Decision Support System, Coronary Artery Disease, Valve Heart Disease

Intervention / Treatment
-----------------
* Other: Computer based Antimicrobial stewardship (AMS) intervention system


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Over 18 years of age; Receiving at least one open-chest cardiovascular surgery during the same admission. Exclusion Criteria: Intravenous or oral antimicrobial use within two weeks before surgery; Emergent/urgent surgery; Admitted for isolated stenting or heart transplantation or implantation of ventricular assist device or implantation of extracorporeal membrane oxygenation; Admitted for subacute bacterial endocarditis; Length of ICU stay over 48 hours.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Health Services Research
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: parallel
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: CDSS-Antimicrobial stewardship<br>Computer-based, multicomponent intervention targeting on reduction of perioperative antimicrobial use will be delivered to teams in the intervention arm. | Other: Computer based Antimicrobial stewardship (AMS) intervention system<br>* Re-evaluation alerts and decision support for the duration of antimicrobial treatment. Re-evaluation alerts and decision support for the choice of antimicrobial. Quality control audit and feedback.<br>|
| No Intervention: Standard of care<br>Teams in the control arm will continue with usual standard clinical care. | |

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Days of antimicrobial therapy (DOT) per admission | DOT represents a specific antibiotic administered to an individual patient on a calendar day independent of dose and route. | From the date of admission to the date of discharge, assessed up to 3 months. | 
| DOT per 1000 patient-days (PD) | DOT per 1000 patient-days | From the date of admission to the date of discharge, assessed up to 60 days. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Drug usage (DDDs) per 100 PD | Items issued × Amount of drug per item per 100 PD | From the date of admission to the date of discharge, assessed up to 60 days. | 
| Drug usage (DDDs) per admission | Items issued × Amount of drug per item per admission | From the date of admission to the date of discharge, assessed up to 60 days. | 
| Length of therapy (LOT) per 100 PD | Number of days during which antimicrobial is used per 100 PD | From the date of admission to the date of discharge, assessed up to 60 days. | 
| Length of therapy (LOT) per admission | Number of days during which antimicrobial is used per admission | From the date of admission to the date of discharge, assessed up to 60 days. | 
| Days per treatment period overall and for specific indications | treatment period: antibiotic treatment not interrupted by more than one calendar day or discharge. | From the date of admission to the date of discharge, assessed up to 60 days. | 
| Rate of participants with clostridium difficile colitis | Colitis associated with Clostridium difﬁcile infection | From the date of admission to the date of discharge, assessed up to 60 days. | 
| Incident clinical cultures with multidrug resistant organisms (MRSA, ESBL-E, CRE, VRE, or Pseudomonas aeruginosa) per 1000 PD and admission. | MRSA=methicillin-resistant Staphylococcus aureus; ESBL-E=extended spectrum beta-lactamase producing Enterobacteriaceae; CRE=Carbapenem resistant Enterobacteriaceae; VRE=vancomycin-resistant enterococci. | From the date of admission to the date of discharge, assessed up to 60 days. | 
| In-hospital or 30-day surgical site infections (SSIs) | Occurs within 30 days postoperatively and involves skin or subcutaneous tissue of the incision and at least one of the following: (1) purulent drainage from the incision, (2) organisms isolated from an aseptically obtained culture of fluid or tissue from the incision, (3) at least one of the following signs or symptoms of infection: pain or tenderness, localized swelling, redness, or heat, and incision is deliberately opened by surgeon and is culture-positive or not cultured (a culture-negative finding does not meet this criterion), and (4) diagnosis of SSI by the surgeon or attending physician. | 30 days from accomplished of the surgery. | 
| Rate of in-hospital bloodstream infections | Blood stream infection after surgery (ICD 10: A41.9) | From the date of admission to the date of discharge, assessed up to 60 days. | 
| Rate of in-hospital pneumonia | Pulmonary infection after surgery (ICD 10：J98.402) | From the date of admission to the date of discharge, assessed up to 60 days. | 
| In-hospital or 30-day mortality, postoperative | mortality with in 30-day after the surgery | 30 days from accomplished of the surgery or within hospital. | 
| In-hospital or 30-day myocardial infarction (MI), postoperative and newly onset | MI (in accordance with the fourth edition of MI definition) was termed type 5 MI, procedure related MI. Briefly, the criteria are as follows: Elevation of cardiac troponin (cTn)>10 times of the 9th percentile upper reference limit with patients with normal baseline; For patients with elevated preprocedural cTn values, elevation of cTn>10 fold increase and manifest a change from the baseline value of over 20%; With as least one of the following: Development of new pathological Q waves; Imaging evidence of loss of viable myocardium that is presumed to be new and in a pattern consistent with an ischemic aetiology; Angiographic findings consistent with a procedural flow-limiting complication. | 30 days from accomplished of the surgery or within hospital. | 
| In-hospital or 30-day stroke, postoperative and newly onset | Stroke refers to newly onset stroke after surgery (ICD 10: I60.0-I60.9; I61.0-I61.9; I62.0; I62.1; I62.9; I63.0-I63.9; I64) | 30 days from accomplished of the surgery or within hospital | 
| In-hospital or 30-day acute kidney injury (AKI) , postoperative and newly onset | AKI refers to newly onset AKI after surgery Acute renal dysfunction within 48 hours (ICD 10: N17); AKI stage I: creatinine≥26.5µmol/L; creatinine over 1.5-1.9 times of baseline value; urine output<0.5ml/kg/hour for 6-12 | 30 days from accomplished of the surgery or within hospital | 
| Length of hospital stay (LOS) | Length of hospital stay (LOS) | From the date of admission to the date of discharge, assessed up to 60 days. | 
| Costs of administered antimicrobials (overall and by class) per admission | Costs of administered antimicrobials (overall and by class) per admission | From the date of admission to the date of discharge, assessed up to 60 days. | 
| Total costs of hospitalization | Total costs of hospitalization | From the date of admission to the date of discharge, assessed up to 60 days. | 
| User satisfaction with the system | Using questionnaire and an interview guide for the process evaluation of the intervention system. | From the date of inclusion of the first patient to the date of discharge of the last patient, assessed up to 12 months. | 
| User compliance with the system | Ccompliance with the multicomponent intervention protocols will be assessed. This will be done by evaluating the total number of times the intervention tools fail to change the physicians' decision on antimicrobial prescription over the intervention period. | From the date of inclusion of the first patient to the date of discharge of the last patient, assessed up to 12 months. |