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

Sponsor

University of Alberta (Other)

Overall Status

Active, not recruiting

CT.gov ID

NCT04896866

Collaborator

(none)

833

Enrollment

Locations

Arms

Anticipated Duration (Months)

277.7

Patients Per Site

12.6

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Covid19 COVID-19 Pneumonia COVID-19 Lower Respiratory Infection COVID-19 Acute Respiratory Distress Syndrome SARS-CoV2 Infection SARS-CoV-2 Acute Respiratory Disease	Behavioral: Antimicrobial stewardship prospective audit and feedback	N/A

Study Design

Study Type:

Interventional

Actual Enrollment :

833 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

Hospital beds are randomized prior to enrolment to intervention versus observation. Intervention consists of antimicrobial stewardship prospective audit and feedback.Hospital beds are randomized prior to enrolment to intervention versus observation. Intervention consists of antimicrobial stewardship prospective audit and feedback.

Masking:

None (Open Label)

Primary Purpose:

Other

Official Title:

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

Actual Study Start Date :

Mar 1, 2021

Actual Primary Completion Date :

Oct 15, 2021

Anticipated Study Completion Date :

Dec 31, 2022

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Antimicrobial stewardship 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 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.
No Intervention: No antimicrobial stewardship No antimicrobial stewardship prospective audit and feedback.

Arm

Intervention/Treatment

Experimental: Antimicrobial stewardship

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

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.

No Intervention: No antimicrobial stewardship

No antimicrobial stewardship prospective audit and feedback.

Outcome Measures

Primary Outcome Measures

Ordinal scale [Day 15 of hospital admission]
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.

Secondary Outcome Measures

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

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Misericordia Community Hospital	Edmonton	Alberta	Canada	T5R 4H5
2	University of Alberta Hospital	Edmonton	Alberta	Canada	T6G 2B7
3	Grey Nuns Community Hospital	Edmonton	Alberta	Canada	T6L 5X8