Clinical trial NCT04591210: The COVID-RASi Trial (COVID-19)
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
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE3
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
Angiotensin receptor blockers
ARB
Lead sponsor: Ottawa Heart Institute Research Corporation
Sponsor class: OTHER
First posted: 2020-10-19
Enrollment: 1155
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Death
timeFrame: 28 days
measure: Mechanical ventilation
timeFrame: 28 days
measure: ICU admission
timeFrame: 28 days
measure: Major Adverse Cardiac Events (MACE)
timeFrame: 28 days
measure: Hospitalizations
timeFrame: 28 days
measure: Quality of life of study participants
timeFrame: 1 year
measure: Quality of life of study participants
timeFrame: 1 year
Secondary outcomes:
measure: Days alive and out of hospital
timeFrame: 30 days
measure: Days alive and out of hospital
timeFrame: 180 days
measure: Cardiovascular mortality
timeFrame: 1 year
measure: All cause hospitalization
timeFrame: 1 year
measure: Percent of patients require intensive care
timeFrame: 1 year
measure: Percent of patients requiring ventilation
timeFrame: 1 year
measure: Percent of patients requiring dialysis
timeFrame: 1 year
Other outcomes:
Locations:
city: Maceio
country: Brazil
facility: Centro de Pesquisa Clinicas Dr Marco Mota
state: Alagoas
city: Itabuna
country: Brazil
facility: Santa Casa de Itabuna
state: Bahia
city: Fortaleza
country: Brazil
facility: Centro de Pesquisas em Diabetes e Doencas Endocrino-Metabolicas
state: CE
city: Belo Horizonte
country: Brazil
facility: Hospital Felicio Rocho
state: MG
city: Campo Grande
country: Brazil
facility: Centro de Pesquisa Clinica da Unimed Campo Grande
state: MG
city: Campo Grande
country: Brazil
facility: Clinica de Campo Grande
state: MG
city: Curitiba
country: Brazil
facility: Nucleo de Pesquisa Clinica SS
state: Parana
city: Recife
country: Brazil
facility: Hospital Agamenom Magalhaes
state: PE
city: Recife
country: Brazil
facility: Pronto Socorro Cardiologico de Pernambuco Recife
state: PE
city: Estancia
country: Brazil
facility: Hospital Eduardo Campos da Pessoa Idosa
state: Recife
city: Natal
country: Brazil
facility: Instituto Atena de Pesquisa Clinica
state: RN
city: Canoas
country: Brazil
facility: Hospital Universitar Canoas
state: RS
city: Passo Fundo
country: Brazil
facility: Hospital Sao Vicente de Paulo
state: RS
city: Porto Alegre
country: Brazil
facility: Hospital Sao Lucas da PUCRS
state: RS
city: Bragança Paulista
country: Brazil
facility: Hospital Universitario Sao Francisco na Providencia de Deus
state: Sao Paulo
city: Campinas
country: Brazil
facility: Instituto de Pesquisa Clinica de Campinas
state: SP
city: Consolacao
country: Brazil
facility: Hospital Bela Vista
state: SP
city: Sao Paulo
country: Brazil
facility: Instituto Prevent Senior
state: SP
city: São Paulo
country: Brazil
facility: Hospital de Julho
state: SP
city: São Paulo
country: Brazil
facility: Instituto de Coracao
state: SP
city: Goiânia
country: Brazil
facility: Instituto Goiano de Oncologia e Hematologia
city: Edmonton
country: Canada
facility: Alberta Health Services
state: Alberta
city: Ottawa
country: Canada
facility: University of Ottawa Heart Institute
state: Ontario
city: Azcapotzalco
country: Mexico
facility: Hospital de Infectologia Dr Daniel Mendez Fernandez
state: Ciudad De Mexico
city: Ecatepec de Morelos
country: Mexico
facility: Unidad de Medicina Familiar No 77
state: Estado De Mexico
city: La Margarita
country: Mexico
facility: Hospital General de Zona 20
state: Puebla
city: El Marques
country: Mexico
facility: Hospital General Regional No 2
state: Queretaro
city: Xalapa
country: Mexico
facility: Hospital General zona 11
state: Veracruz
city: Xalapa
country: Mexico
facility: Unidad de Medicina Familiar No 10
state: Veracruz
city: Ciudad de Mexico
country: Mexico
facility: Hospital General 1, IMSS
city: Ciudad de Mexico
country: Mexico
facility: Hospital General de zona 27- IMSS
Study officials:
affiliation: Ottawa Heart Institute Research Corporation
name: Peter Liu, MD
role: PRINCIPAL_INVESTIGATOR
References: