Host Response Mediators in Coronavirus (COVID-19) Infection - Is There a Protective Effect of Losartan and Other ARBs on Outcomes of Coronavirus Infection?

Summary

SARS-CoV-2 is a member of a class of viruses: angiotensin converting enzyme 2 (ACE2)-binding viruses that study calls "ABVs". The World Health Organization (WHO) and others are performing randomized controlled trials (RCTs) of vaccines and novel antivirals to address SARS-CoV-2 directly. However, the critical illness complications of COVID-19 are caused in part by SARS-CoV-2's binding and inhibiting ACE2 and the consequent host response.

ACE 2 is the receptor for H1N1, H5N1, and SARS-CoV-2. After binding ACE2, SARS-CoV-2 is endocytosed, and surface ACE2 is down-regulated, increasing angiotensin II (ATII a potent vasoconstrictor) in COVID-19. The original ARBs limits lung injury in murine influenza H7N9 and decreases viral titre and RNA.

Study has a unique opportunity to complement vaccine and anti-viral RCTs with an RCT modulating the host response using an angiotensin II type 1 receptor blocker (ARBs) to decrease the mortality of hospitalized COVID-19 patient.

Conditions

• Covid19
• SARS-CoV Infection

Interventions

DRUG

Losartan

Oral losartan 25 mg, stepped up to 50 mg and then up to 100 mg peak dose, as tolerated.

DRUG

Valsartan

Oral Valsartan 40 mg, stepped up to 80 mg and then up to 160 mg peak dose, as tolerated.

DRUG

Azilsartan

Oral Azilsartan 40 mg, and stepped up to 80 mg.

DRUG

Candesartan

Oral Candesartan 8 mg, stepped up to 16 mg and then up to 32 mg peak dose, as tolerated.

DRUG

Eprosartan

Oral Eprosartan 400 mg, stepped up to 600 mg and then up to 800 mg peak dose, as tolerated.

DRUG

Irbesartan

Oral Irbesartan 75 mg, stepped up to 150 mg and then up to 300 mg peak dose, as tolerated.

DRUG

Olmesartan

Oral Olmesartan 10 mg, stepped up to 20 mg and then up to 40 mg peak dose, as tolerated.

DRUG

Telmisartan

Oral Azilsartan 40 mg, and stepped up to 80 mg.

Sponsors & Collaborators

• Canadian Institutes of Health Research (CIHR)

  collaborator OTHER_GOV

• University of British Columbia

  lead OTHER

Principal Investigators

• James A Russell, MD · University of British Columbia

• Karen Tran, MD · University of British Columbia

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Model

PARALLEL

Eligibility

Min Age

18 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2020-10-09

Primary Completion

2022-04-22

Completion

2022-04-22

Countries

• Canada
• France

Study Locations