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.
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.
Drug: Angiotensin converting enzyme inhibitor
The study recommends physicians to select an ACEi with proven benefit in cardiovascular diseases such as perindopril, ramipril or enalapril. Lab values will be obtained during baseline. The patient will be followed by the physician clinically, with recommended laboratory testing in one week, including renal function, potassium assessment, and dose adjustments as appropriate.
Drug: Angiotensin II Receptor Blockers
The study recommends physicians to select evidence-based ARBs such as candesartan or valsartan or losartan. Lab values will be obtained during baseline. The patient will be followed by the physician clinically, with recommended laboratory testing in one week, and dose adjustments as appropriate.
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
Centro de Pesquisa Clinicas Dr Marco Mota
Maceio, Alagoas, Brazil
Santa Casa de Itabuna
Itabuna, Bahia, Brazil
Centro de Pesquisas em Diabetes e Doencas Endocrino-Metabolicas
Fortaleza, CE, Brazil
Hospital Felicio Rocho
Belo Horizonte, MG, Brazil
Centro de Pesquisa Clinica da Unimed Campo Grande
Campo Grande, MG, Brazil
Clinica de Campo Grande
Campo Grande, MG, Brazil
Nucleo de Pesquisa Clinica SS
Curitiba, Parana, Brazil
Hospital Agamenom Magalhaes
Recife, PE, Brazil
Pronto Socorro Cardiologico de Pernambuco Recife
Recife, PE, Brazil
Hospital Eduardo Campos da Pessoa Idosa
Estancia, Recife, Brazil
Instituto Atena de Pesquisa Clinica
Natal, RN, Brazil
Hospital Universitar Canoas
Canoas, RS, Brazil
Hospital Sao Vicente de Paulo
Passo Fundo, RS, Brazil
Hospital Sao Lucas da PUCRS
Porto Alegre, RS, Brazil
Hospital Universitario Sao Francisco na Providencia de Deus
Bragança Paulista, Sao Paulo, Brazil
Instituto de Pesquisa Clinica de Campinas
Campinas, SP, Brazil
Hospital Bela Vista
Consolacao, SP, Brazil
Instituto Prevent Senior
Sao Paulo, SP, Brazil
Hospital de Julho
São Paulo, SP, Brazil
Instituto de Coracao
São Paulo, SP, Brazil
Instituto Goiano de Oncologia e Hematologia
Goiânia, Brazil
Alberta Health Services
Edmonton, Alberta, Canada
University of Ottawa Heart Institute
Ottawa, Ontario, Canada
Hospital de Infectologia Dr Daniel Mendez Fernandez
Azcapotzalco, Ciudad De Mexico, Mexico
Unidad de Medicina Familiar No 77
Ecatepec de Morelos, Estado De Mexico, Mexico
Hospital General de Zona 20
La Margarita, Puebla, Mexico
Hospital General Regional No 2
El Marques, Queretaro, Mexico
Hospital General zona 11
Xalapa, Veracruz, Mexico
Unidad de Medicina Familiar No 10
Xalapa, Veracruz, Mexico
Hospital General 1, IMSS
Ciudad de Mexico, Mexico
Hospital General de zona 27- IMSS
Ciudad de Mexico, Mexico
Peter Liu, MD, Principal Investigator
Ottawa Heart Institute Research Corporation