Elimination or Prolongation of ACE Inhibitors and ARB in Coronavirus Disease 2019

Summary

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus responsible for coronavirus disease 2019 (COVID-19), is associated with a high incidence of acute respiratory distress syndrome (ARDS) and death. Hypertension and cardiovascular disease are risk factors for death in COVID-19. Angiotensin converting enzyme 2 (ACE2), an important component of the renin-angiotensin system, serves as the binding site of SARS-CoV-2 and facilitates host cell entry in the lungs. In experimental models, angiotensin converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) have been shown to increase ACE2 expression in several organs, potentially promoting viral cell invasion, although these findings are not consistent across studies. Alternatively, ACEIs and ARBs may actually improve mechanisms of host defense or hyperinflammation, ultimately reducing organ injury. Finally, ACEIs and ARBs may have direct renal, pulmonary and cardiac protective benefits in the setting of COVID-19. Therefore, it is unclear if ACEIs and ARBs may be beneficial or harmful in patients with COVID-19. Given the high prevalence of hypertension, cardiovascular and renal disease in the world, the high prevalence of ACEIs or ARBs in these conditions, and the clinical equipoise regarding the continuation vs. discontinuation of ACEIs/ARBs in the setting of COVID, a randomized trial is urgently needed. The aim of this trial is to assess the clinical impact of continuation vs. discontinuation of ACE inhibitors and angiotensin receptor blockers on outcomes in patients hospitalized with COVID-19.

Conditions

• COVID-19

Interventions

OTHER

Discontinuation of ARB/ACEI

The randomized intervention will be the discontinuation of ACEI/ARBs. In all participants randomized to discontinuation, treating clinicians will be reminded about the medication discontinuation upon discharge and will be prompted to consider re-initiation of the medication at that time if appropriate, per the clinician's discretion.

OTHER

Continuation of ARB/ACEI

The randomized intervention will be the continuation of ACEI/ARBs at the doses previously prescribed for patients during their routine care. Clinicians will be encouraged to continue the randomized treatment but will be allowed to change the dose of ACEI/ARB or discontinue these medications if any compelling clinical reasons are identified (such as hypotension, hyperkalemia, acute kidney injury).

Sponsors & Collaborators

• Jordana B. Cohen, MD, MSCE

  collaborator UNKNOWN

• Hanff, Thomas C., M.D., MPH

  collaborator INDIV

• University of Arizona

  collaborator OTHER

• Hospital Nacional Carlos Alberto Seguin Escobedo - EsSalud

  collaborator OTHER

• Hospital Nacional Edgardo Rebagliati Martins

  collaborator OTHER

• Hospital Español de Mendoza

  collaborator OTHER

• Stanford University

  collaborator OTHER

• Ottawa Hospital Research Institute

  collaborator OTHER

• Hospital Civil de Guadalajara

  collaborator OTHER

• Universidad Catolica Argentina

  collaborator OTHER

• Caja Nacional de Salud

  collaborator OTHER

• Departamento de Medicina, Hospital Alberto Barton Thompson, Callao, Peru

  collaborator OTHER

• Karolinska Institutet

  collaborator OTHER

• University of Miami

  collaborator OTHER

• Division of Cardiology, Department of Medicine, Hospital Español, Buenos Aires, Argentina

  collaborator OTHER

• University of Michigan

  collaborator OTHER

• Jesse Chittams, MS

  collaborator UNKNOWN

• Duke University

  collaborator OTHER

• Vasquez, Charles R., M.D.

  collaborator INDIV

• University of Pennsylvania

  lead OTHER

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

SINGLE

Model

PARALLEL

Eligibility

Min Age

18 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2020-03-31

Primary Completion

2020-08-20

Completion

2020-08-20

Countries

• United States

Study Locations