Efficacy and Safety of Antimicrobial Stewardship Intervention in Hospitalized COVID-19 Patients (COVASP)

Study Overview
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Brief Summary
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COVID-19 is respiratory disease caused by the severe acute respiratory coronavirus 2 (SARS-CoV-2), a novel coronavirus which has spread rapidly across the world with over 149.9 million laboratory confirmed cases and over 3.1 million reported deaths since December 2019. Approximately 4-8% of hospitalized patients with COVID-19 have co-infection with bacterial pathogens however there is widespread and often broad-spectrum antibiotic use in these patients. This is a prospective, multi-center, non-inferiority pragmatic clinical trial of antimicrobial stewardship prospective audit and feedback versus no antimicrobial stewardship intervention on physicians attending to patients with proven SARS-CoV-2 infection confirmed by nucleic acid testing in the preceding 2 weeks of hospitalization for acute COVID-19 pneumonia. Prospective audit and feedback is the real time review of antibacterial prescriptions and immediate feedback to prescribers to optimize antimicrobial prescriptions. Hospital beds will be stratified by COVID unit and critical care unit beds, and will be computer randomized in a 1:1 fashion into 2 arms (antimicrobial stewardship intervention versus no antimicrobial stewardship intervention) prior to study commencement at the participating site. Patients hospitalized to study-eligible beds will be followed for primary and secondary outcomes. The objective of this study is to determine the effect of an antimicrobial stewardship intervention (prospective audit and feedback) on clinical outcomes in patients hospitalized with acute COVID-19.

Official Title
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Efficacy and Safety of Antimicrobial Stewardship Intervention in Hospitalized COVID-19 Patients: A Pragmatic Clinical Trial

Conditions
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Covid19, COVID-19 Pneumonia, COVID-19 Lower Respiratory Infection, COVID-19 Acute Respiratory Distress Syndrome, SARS-CoV2 Infection, SARS-CoV-2 Acute Respiratory Disease

Intervention / Treatment
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* Behavioral: Antimicrobial stewardship prospective audit and feedback


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age ≥18 years at the time of hospital admission. Confirmed SARS-CoV-2 infection by nucleic acid testing in the preceding 14 days of hospital admission. Admitted from the community (including continuing care facilities). Admitted to a hospital bed designated in the study. SpO2 ≤94% requiring supplemental oxygen or chest imaging findings compatible with COVID-19 pneumonia. Exclusion Criteria: The patient is enrolled in another clinical trial that involves antibacterial therapy. The patient's goals of care is anticipated to be designated total compassionate care or palliative care within 48 hours of admission. The patient's progression to death is anticipated to be imminent and inevitable within 48 hours of admission. The patient was attended by any member of the research team within 30 days of enrollment. The patient is transferred from another acute care center.

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: Other
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Hospital beds are randomized prior to enrolment to intervention versus observation. Intervention consists of antimicrobial stewardship prospective audit and feedback.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Antimicrobial stewardship<br>Antimicrobial stewardship prospective audit and feedback on physicians attending to patients admitted with community-acquired COVID-19 pneumonia to beds randomized to antimicrobial stewardship intervention. | Behavioral: Antimicrobial stewardship prospective audit and feedback<br>* Audits are performed on weekdays, less statutory holidays, by members of the antimicrobial stewardship team consisting of infectious disease or antimicrobial stewardship physicians or pharmacists. Verbal and written feedback will be provided in real-time. Initial prospective audit and feedback (PAF) will occur on the day of enrolment. Follow-up PAF will occur weekly (+/-3 days to account for weekends or statuary holidays) and ad-hoc if a new antibacterial is prescribed, until the primary end-point. Appropriateness will be assessed based on local clinical practice guidelines. Only antibacterials will be audited. Prescriptions will be excluded from PAF if they are single doses or discontinued prior to PAF. Prescriptions will be also be excluded from PAF and the final analysis if being used for surgical or medical prophylaxis.<br>|
| No Intervention: No antimicrobial stewardship<br>No antimicrobial stewardship prospective audit and feedback. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Ordinal scale | A 7 point ordinal scale of clinical outcomes: point - Not hospitalized, able to resume normal daily activities points - Not hospitalized, unable to resume normal daily activities points - Hospitalized, not on supplemental oxygen points - Hospitalized, on supplemental oxygen points - Hospitalized, on high flow oxygen therapy or non-invasive mechanical ventilation points - Hospitalized, on ECMO or invasive mechanical ventilation points - Death Higher scores means a worse outcome. | Day 15 of hospital admission | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Length of hospital stay | Duration of hospitalization in days | through study completion, an average of 5 days | 
| In-hospital mortality | Death occurring during hospital admission | through study completion, an average of 5 days | 
| 30-day mortality | Mortality in the first 30 days after diagnosis | 30 days | 
| 30-day C. difficile associated mortality | Death related to C. difficile-associated diarrhea in the first 30 days after diagnosis | 30 days | 
| 30 day re-admission rate | Re-admission to hospital after initial discharge in the first 30 days after diagnosis | 30 days from hospital discharge | 
| Days of therapy normalized for patient-days | Days of antibiotic therapy normalized for patients-day | capped at 30 days of hospitalization | 
| Length of total antimicrobial therapy normalized for patient-days | Length of antibiotics normalized for patient-days | capped at 30 days of hospitalization | 
| Number of antimicrobial stewardship audits | Number of audits by ASP | through study completion, an average of 5 days | 
| Number of antimicrobial stewardship recommendations | Number of recommendations by ASP | through study completion, an average of 5 days | 
| Antimicrobial stewardship acceptance rates | Acceptance rate of ASP recommendations | through study completion, an average of 5 days | 
| Multi-drug resistant bacteria infection rates | Development of multi-drug resistant bacterial infection in the first 30 days after diagnosis | 30 days | 
| Clostridioides difficile infection rate | C. difficile-associated diarrhea in the first 30 days after diagnosis | 30 days | 
| Percentage of participants with neutropenia | Occurrence of neutropenia in the first 30 days | 30 days | 
| Acute kidney injury | diagnosed and staged as according to KDIGO | 30 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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antimicrobial stewardship, antibiotic stewardship, prospective audit and feedback, quality improvement, antibiotics