COVID-19Phase 3NCT04591210
The COVID-RASi Trial (COVID-19)
A Phase 3 study testing Angiotensin converting enzyme inhibitor and Angiotensin II Receptor Blockers in people with COVID-19 and Cardiovascular Diseases, run by Ottawa Heart Institute Research Corporation at 31 sites in 3 countries.
Trial summary
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)… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- COVID-19, Cardiovascular Diseases
- What is being tested?
- Angiotensin converting enzyme inhibitor and Angiotensin II Receptor Blockers
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 372 participants
- Where
- 31 sitesin 3 countries
- Study dates
- 27 Jan 2021to 30 Dec 2024
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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 locations and contacts
31 sites in 3 countries.
31 sites in 3 countries
Brazil21 sites
Hospital Felicio Rocho
Belo Horizonte, Minas Gerais
Hospital Universitario Sao Francisco na Providencia de Deus
Bragança Paulista, São Paulo, 12916-542
Instituto de Pesquisa Clinica de Campinas
Campinas, São Paulo
Centro de Pesquisa Clinica da Unimed Campo Grande
Campo Grande, Minas Gerais
Clinica de Campo Grande
Campo Grande, Minas Gerais
Hospital Universitar Canoas
Canoas, Rio Grande do Sul
Hospital Bela Vista
Consolação, São Paulo
Nucleo de Pesquisa Clinica SS
Curitiba, Paraná, 80730-150
Hospital Eduardo Campos da Pessoa Idosa
Estância, Recife, 50870-901
Centro de Pesquisas em Diabetes e Doencas Endocrino-Metabolicas
Fortaleza, Ceará, 60-430-350
Instituto Goiano de Oncologia e Hematologia
Goiânia
Santa Casa de Itabuna
Itabuna, Estado de Bahia
Centro de Pesquisa Clinicas Dr Marco Mota
Maceió, Alagoas
Instituto Atena de Pesquisa Clinica
Natal, Rio Grande do Norte
Hospital Sao Vicente de Paulo
Passo Fundo, Rio Grande do Sul
Hospital Sao Lucas da PUCRS
Porto Alegre, Rio Grande do Sul, 90610-000
Hospital Agamenom Magalhaes
Recife, Pernambuco
Pronto Socorro Cardiologico de Pernambuco Recife
Recife, Pernambuco
Hospital de Julho
São Paulo, São Paulo, 01409-901
Instituto de Coracao
São Paulo, São Paulo
Instituto Prevent Senior
São Paulo, São Paulo
Mexico8 sites
Hospital de Infectologia Dr Daniel Mendez Fernandez
Azcapotzalco, Mexico City, 06900
Unidad de Medicina Familiar No 77
Ecatepec de Morelos, State of Mexico
Hospital General Regional No 2
El Marqués, Querétaro, 76269
Hospital General de Zona 20
La Margarita, Puebla, 72560
Hospital General 1, IMSS
Mexico City
Hospital General de zona 27- IMSS
Mexico City
Hospital General zona 11
Xalapa, Veracruz, 91000
Unidad de Medicina Familiar No 10
Xalapa, Veracruz, 91000
Canada2 sites
Alberta Health Services
Edmonton, Alberta
University of Ottawa Heart Institute
Ottawa, Ontario
About this study
Official title: 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.
Read the 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.
- Conditions
- COVID-19, Cardiovascular Diseases
- Being tested
- Angiotensin converting enzyme inhibitor, Angiotensin II Receptor Blockers
- Keywords
- cardiovascular risk factors, corona virus, COVID-19, severe acute respiratory syndrome coronavirus 2 (SARS-COV-2), Angiotensin-converting enzyme inhibitors, ACEi, Renin-angiotensin system inhibitors, RASi, Angiotensin receptor blockers, ARB
- Medical subject headings
- COVID-19, Cardiovascular Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Angiotensin converting enzyme inhibitorDrug
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.
Angiotensin II Receptor BlockersDrug
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.
| Study group | Role | What they receive |
|---|---|---|
| No Treatment (Standard of Care) | No intervention | 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 | The physician will initiate any ACE inhibitor and dose at their discretion. Receives: Drug: Angiotensin converting enzyme inhibitor |
| ARB treatment | Experimental | The physician will initiate any ARB and dose at their discretion. Receives: Drug: Angiotensin II Receptor Blockers |
What is being measured
The primary outcome is the main question the study is designed to answer.
Death
Within first 28 days post randomization
Measured: 28 days
Mechanical ventilation
Within first 28 days post randomization
Measured: 28 days
ICU admission
Within first 28 days post randomization
Measured: 28 days
Major Adverse Cardiac Events (MACE)
Within first 28 days post randomization
Measured: 28 days
Hospitalizations
Within first 28 days post randomization
Measured: 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
Measured: 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
Measured: 1 year
Secondary outcomes (7)
Days alive and out of hospital
Measured: 30 days
Days alive and out of hospital
Measured: 180 days
Cardiovascular mortality
Measured: 1 year
All cause hospitalization
Measured: 1 year
Percent of patients require intensive care
Measured: 1 year
Percent of patients requiring ventilation
Measured: 1 year
Percent of patients requiring dialysis
Measured: 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Oct 2020
- Study start27 Jan 2021
- Primary completion30 Dec 2024
- Study completion30 Dec 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for COVID-19Studies of the same condition, open and under way.
- More trials run by Ottawa Heart Institute Research CorporationThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 372 participants (actual)
Sponsor and investigators
- Lead sponsor
- Ottawa Heart Institute Research Corporation
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Peter Liu, MD, Principal investigator, Ottawa Heart Institute Research Corporation
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04591210
- Sponsor's protocol ID
- CTO-3212
- Status last verified
- Jan 2026
- First submitted
- 6 Oct 2020
- Last updated
- 28 Jan 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 28 Jan 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Evaluation of the Potential Benefit of Renin-angiotensin System Inhibitors (RASi, ACEi/ARB) in High-risk Patients With COVID-19. The COVID-RASi Trial
- ClinicalTrials.gov ID
- NCT04591210
- Acronym / sponsor ID
- CTO-3212
- Conditions
- COVID-19, Cardiovascular Diseases
- Keywords
- cardiovascular risk factors, corona virus, COVID-19, severe acute respiratory syndrome coronavirus 2 (SARS-COV-2), Angiotensin-converting enzyme inhibitors, ACEi, Renin-angiotensin system inhibitors, RASi
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 372 participants (actual)
- Lead sponsor
- Ottawa Heart Institute Research CorporationUniversity, hospital or other
- Study start
- 27 Jan 2021 (actual)
- Primary completion
- 30 Dec 2024 (actual)
- Study completion
- 30 Dec 2024 (actual)
- First posted
- 19 Oct 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| No Treatment (Standard of Care) | No intervention | –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 | Drug: Angiotensin converting enzyme inhibitorThe physician will initiate any ACE inhibitor and dose at their discretion. |
| ARB treatment | Experimental | Drug: Angiotensin II Receptor BlockersThe physician will initiate any ARB and dose at their discretion. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (2 listed)
- 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
Key exclusion criteria (8 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Angiotensin converting enzyme inhibitorThe 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 | ACEi treatment |
| Angiotensin II Receptor BlockersThe 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. | Drug | ARB treatment |
Primary outcome
Death
Time frame: 28 days
Within first 28 days post randomization
Mechanical ventilation
Time frame: 28 days
Within first 28 days post randomization
ICU admission
Time frame: 28 days
Within first 28 days post randomization
Major Adverse Cardiac Events (MACE)
Time frame: 28 days
Within first 28 days post randomization
Hospitalizations
Time frame: 28 days
Within first 28 days post randomization
Quality of life of study participants
Time frame: 1 year
Assessed by ongoing symptoms and standardized questionnaires, scale to assess overall health 1-100, 100 is the best, higher score means better outcome
Quality of life of study participants
Time frame: 1 year
Assessed by ongoing symptoms and standardized questionnaires- scale to assess overall health 1-100, 100 is the best, higher score means better outcome
7 secondary outcomes
Days alive and out of hospital
Time frame: 30 days
Days alive and out of hospital
Time frame: 180 days
Cardiovascular mortality
Time frame: 1 year
All cause hospitalization
Time frame: 1 year
Percent of patients require intensive care
Time frame: 1 year
Percent of patients requiring ventilation
Time frame: 1 year
Percent of patients requiring dialysis
Time frame: 1 year
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Jan 2026.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Peter Liu, MD principal investigator
Ottawa Heart Institute Research Corporation
31 sites in 3 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Angiotensin converting enzyme inhibitor and Angiotensin II Receptor Blockers in people with COVID-19 and Cardiovascular Diseases, run by Ottawa Heart Institute Research Corporation at 31 sites in 3 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 28 Jan 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 31 sites in Brazil, Mexico, Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Death (time frame: 28 days). The study lists 7 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Jan 2026.