The COVID-RASi Trial (COVID-19)

COVID-19 Clinical Trial

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04591210
• Other study ID #: CTO-3212
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: January 27, 2021
• Est. completion date: December 2025

Study information

• Verified date: February 2024
• Source: Ottawa Heart Institute Research Corporation
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical 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) 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.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 1155
• Est. completion date: December 2025
• Est. primary completion date: December 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Cardiovascular Diseases
• COVID-19

Intervention

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.
• 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.

Locations

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

Sponsors (1)

Lead Sponsor	Collaborator
Ottawa Heart Institute Research Corporation

Countries where clinical trial is conducted

Brazil,  Canada,  Mexico, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Death	Within first 28 days post randomization	28 days
Primary	Mechanical ventilation	Within first 28 days post randomization	28 days
Primary	ICU admission	Within first 28 days post randomization	28 days
Primary	Major Adverse Cardiac Events (MACE)	Within first 28 days post randomization	28 days
Primary	Hospitalizations	Within first 28 days post randomization	28 days
Primary	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
Primary	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	Days alive and out of hospital		30 days
Secondary	Days alive and out of hospital		180 days
Secondary	Cardiovascular mortality		1 year
Secondary	All cause hospitalization		1 year
Secondary	Percent of patients require intensive care		1 year
Secondary	Percent of patients requiring ventilation		1 year
Secondary	Percent of patients requiring dialysis		1 year