The COVID-RASi Trial (COVID-19)

Evaluation of the Potential Benefit of Renin-angiotensin System Inhibitors (RASi, ACEi/ARB) in High-risk Patients With COVID-19. The COVID-RASi Trial

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Cardiovascular Diseases; COVID-19
• Intervention / Treatment: Drug: Angiotensin converting enzyme inhibitor; Drug: Angiotensin II Receptor Blockers

Detailed 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.

• Study Type: Interventional
• Enrollment (Estimated): 1155
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Ermina Moga; Phone Number: 10945 613-696-7000; Email: EMoga@ottawaheart.ca

Study Locations

• Brazil
  • Goiânia, Brazil
    • Instituto Goiano de Oncologia e Hematologia
  • Alagoas
    • Maceio, Alagoas, Brazil
      • Centro de Pesquisa Clinicas Dr Marco Mota
  • Bahia
    • Itabuna, Bahia, Brazil
      • Santa Casa de Itabuna
  • CE
    • Fortaleza, CE, Brazil, 60-430-350
      • Centro de Pesquisas em Diabetes e Doencas Endocrino-Metabolicas
  • MG
    • Belo Horizonte, MG, Brazil
      • Hospital Felício Rocho
    • Campo Grande, MG, Brazil
      • Centro de Pesquisa Clinica da Unimed Campo Grande
    • Campo Grande, MG, Brazil
      • Clinica de Campo Grande
  • PE
    • Recife, PE, Brazil
      • Hospital Agamenom Magalhaes
    • Recife, PE, Brazil
      • Pronto Socorro Cardiologico de Pernambuco Recife
  • Parana
    • Curitiba, Parana, Brazil, 80730-150
      • Nucleo de Pesquisa Clinica SS
  • RN
    • Natal, RN, Brazil
      • Instituto Atena de Pesquisa Clínica
  • RS
    • Canoas, RS, Brazil
      • Hospital Universitar Canoas
    • Passo Fundo, RS, Brazil
      • Hospital São Vicente de Paulo
    • Porto Alegre, RS, Brazil, 90610-000
      • Hospital São Lucas da PUCRS
  • Recife
    • Estancia, Recife, Brazil, 50870-901
      • Hospital Eduardo Campos da Pessoa Idosa
  • SP
    • Campinas, SP, Brazil
      • Instituto de Pesquisa Clínica de Campinas
    • Consolacao, SP, Brazil
      • Hospital Bela Vista
    • Sao Paulo, SP, Brazil
      • Instituto Prevent Senior
    • São Paulo, SP, Brazil, 01409-901
      • Hospital de Julho
    • São Paulo, SP, Brazil
      • Instituto de Coracao
  • Sao Paulo
    • Bragança Paulista, Sao Paulo, Brazil, 12916-542
      • Hospital Universitario Sao Francisco na Providencia de Deus
• Canada
  • Alberta
    • Edmonton, Alberta, Canada
      • Alberta Health Services
  • Ontario
    • Ottawa, Ontario, Canada
      • University of Ottawa Heart Institute
• Mexico
  • Ciudad de Mexico, Mexico
    • Hospital General 1, IMSS
  • Ciudad de Mexico, Mexico
    • Hospital General de zona 27- IMSS
  • Ciudad De Mexico
    • Azcapotzalco, Ciudad De Mexico, Mexico, 06900
      • Hospital de Infectologia Dr Daniel Mendez Fernandez
  • Estado De Mexico
    • Ecatepec de Morelos, Estado De Mexico, Mexico
      • Unidad de Medicina Familiar No 77
  • Puebla
    • La Margarita, Puebla, Mexico, 72560
      • Hospital General de Zona 20
  • Queretaro
    • El Marques, Queretaro, Mexico, 76269
      • Hospital General Regional No 2
  • Veracruz
    • Xalapa, Veracruz, Mexico, 91000
      • Hospital General zona 11
    • Xalapa, Veracruz, Mexico, 91000
      • Unidad de Medicina Familiar No 10

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
No Intervention: No Treatment (Standard of Care); 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.
Experimental: ACEi treatment; The physician will initiate any ACE inhibitor and dose at their discretion.	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.
Experimental: ARB treatment; The physician will initiate any ARB and dose at their discretion.	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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Death	Within first 28 days post randomization	28 days
Mechanical ventilation	Within first 28 days post randomization	28 days
ICU admission	Within first 28 days post randomization	28 days
Major Adverse Cardiac Events (MACE)	Within first 28 days post randomization	28 days
Hospitalizations	Within first 28 days post randomization	28 days
Quality of life of study participants	Assessed by ongoing symptoms and standardized questionnaires, scale to assess overall health 1-100, 100 is the best, higher score means better outcome	1 year
Quality of life of study participants	Assessed by ongoing symptoms and standardized questionnaires- scale to assess overall health 1-100, 100 is the best, higher score means better outcome	1 year

Secondary Outcome Measures

Outcome Measure	Time Frame
Days alive and out of hospital	30 days
Days alive and out of hospital	180 days
Cardiovascular mortality	1 year
All cause hospitalization	1 year
Percent of patients require intensive care	1 year
Percent of patients requiring ventilation	1 year
Percent of patients requiring dialysis	1 year

Collaborators and Investigators

• Sponsor: Ottawa Heart Institute Research Corporation
• Investigators: Principal Investigator: Peter Liu, MD, Ottawa Heart Institute Research Corporation

Study record dates

Study Major Dates

• Study Start (Actual): January 27, 2021
• Primary Completion (Estimated): December 1, 2024
• Study Completion (Estimated): December 1, 2025

Study Registration Dates

• First Submitted: October 6, 2020
• First Submitted That Met QC Criteria: October 15, 2020
• First Posted (Actual): October 19, 2020

Study Record Updates

• Last Update Posted (Actual): February 2, 2024
• Last Update Submitted That Met QC Criteria: February 1, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Keywords: COVID-19; cardiovascular risk factors; ARB; Angiotensin receptor blockers; corona virus; ACEi; Angiotensin-converting enzyme inhibitors; RASi; severe acute respiratory syndrome coronavirus 2 (SARS-COV-2); Renin-angiotensin system inhibitors
• Additional Relevant MeSH Terms: Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Pneumonia, Viral; Pneumonia; Lung Diseases; COVID-19; Cardiovascular Diseases; Molecular Mechanisms of Pharmacological Action; Protease Inhibitors; Serine Proteinase Inhibitors; Vasoconstrictor Agents; Enzyme Inhibitors; Angiotensin II; Giapreza; Angiotensinogen; Angiotensin-Converting Enzyme Inhibitors; Angiotensin Receptor Antagonists
• Other Study ID Numbers: CTO-3212

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No