The COVID-RASi Trial (COVID-19)

University of Ottawa Heart Institute

Status and phase: Completed; Phase 3

Conditions: COVID-19; Cardiovascular Diseases

Treatments: Drug: Angiotensin II Receptor Blockers; Drug: Angiotensin converting enzyme inhibitor

Study type: Interventional

Funder types: Other

Identifiers

NCT04591210

CTO-3212

Details and patient eligibility

About

The COVID-RASi study is an international randomized clinical trial that will evaluate the potential benefit of angiotensin modulators on clinical outcomes, in COVID-19 patients. The purpose of this study is to determine if renin-angiotensin system inhibitors (RASi), with angiotensin-converting enzyme inhibitors (ACEi) or angiotensin II receptor blockers (ARB), has a beneficial effect in patients with COVID-19 infections, by reducing ICU admission, ventilator requirement or death. We would also like to determine if there are differences between ACEi and ARB therapeutic treatments. With the increasing potential of long COVID symptoms, at the 1 year follow up, a primary endpoint will be the quality of life of study participants, as assessed by ongoing symptoms and/or the standardized questionnaires.

Full description

The goal is to determine if RASi with ACEi or ARB, has a beneficial effect in patients with COVID-19 infections, by reducing hospitalizations, ICU admission, ventilator requirement or death.

This is a multi-centre study, conducted in major centres treating COVID-19 patients in-hospital and in various outpatient settings.

Patients admitted to hospital or outpatients that test positive for COVID-19 and meet the inclusion/exclusion criteria will be eligible to participate in this study. All study participants will not be on RASi (ACEi/ARB) treatment at the time of consent. Participants will be randomized to initiation of ACEi vs ARB treatment vs no RASi treatment as part of care for COVID-19 in a 1:1:1 ratio.

The patient will be followed by their physician according to usual clinical care. Sites will complete research-related follow-ups at 24 hours, 7 and 28 days to asssess patient's clinical status, side effects and the achievement of clinical endpoints by telephone interviews. Phone call follow ups will also be conducted at 6 months and 12 months after enrollment in the study.

Enrollment: 372 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Patient with COVID-19 diagnosis with laboratory confirmation within the last 30 days AND
• Age 40 years old or greater if outpatient OR age 18 years old or greater if inpatient (admitted to the hospital) at time of recruitment

Exclusion criteria

• Contraindication to ARB or ACEi, including severe aortic stenosis and angioedema
• Patients who are currently on active treatment with ARB/ACEi
• Known bilateral renal artery stenosis
• Systolic BP ≤90 mmHg
• eGFR<30 ml/min, if not receiving dialysis treatment
• K>5.5 mmol/L on screening laboratory testing
• Recent history of dizziness, vertigo, related to hypotension or orthostatic hypotension, that can lead to contraindication to ACEI/ARBs
• Acute respiratory distress syndrome requiring invasive ventilation

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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372 participants in 3 patient groups

No Treatment (Standard of Care)

No Intervention group

Description:

Participants will be treated as per standardized care pathway according to province/state and institutional guidelines. Physicians will be reminded not to start ACEi or ARB throughout admission or to outpatients until active study participation is complete at 28 days post symptoms.

ACEi treatment

Experimental group

Description:

The physician will initiate any ACE inhibitor and dose at their discretion.

Treatment:

Drug: Angiotensin converting enzyme inhibitor

ARB treatment

Experimental group

Description:

The physician will initiate any ARB and dose at their discretion.

Treatment:

Drug: Angiotensin II Receptor Blockers