Protocol for a 30-day randomised, parallel-group, non-inferiority, controlled trial investigating the effects of discontinuing renin-angiotensin system inhibitors in patients with and without COVID-19: the RASCOVID-19 trial.

Abstract

INTRODUCTION:

The COVID-19 pandemic caused by the virus SARS-CoV has spread rapidly and caused damage worldwide. Data suggest a major overrepresentation of hypertension and diabetes among patients experiencing severe courses of COVID-19 including COVID-19-related deaths. Many of these patients receive renin-angiotensin system (RAS) inhibiting therapy, and evidence suggests that treatment with angiotensin II receptor blockers (ARBs) could attenuate SARS-CoV-induced acute respiratory distress syndrome, and ACE inhibitors and ARBs have been suggested to alleviate COVID-19 pulmonary manifestations. This randomised clinical trial will address whether RAS inhibiting therapy should be continued or discontinued in hospitalised patients with COVID-19.

METHODS AND ANALYSIS:

This trial is a 30-day randomised parallel-group non-inferiority clinical trial with an embedded mechanistic substudy. In the main trial, 215 patients treated with a RAS inhibitor will be included. The participants will be randomly assigned in a 1:1 ratio to either discontinue or continue their RAS inhibiting therapy in addition to standard care. The patients are included during hospitalisation and followed for a period of 30 days. The primary end point is number of days alive and out of hospital within 14 days after recruitment. In a mechanistic substudy, 40 patients treated with RAS inhibition, who are not in hospital and not infected with COVID-19 will be randomly assigned to discontinue or continue their RAS inhibiting therapy with the primary end point of serum ACE2 activity.

ETHICS AND DISSEMINATION:

This trial has been approved by the Scientific-Ethical Committee of the Capital Region of Denmark (identification no. H-20026484), the Danish Medicines Agency (identification no. 2020040883) and by the Danish Data Protection Agency (P-2020-366). The results of this project will be compiled into one or more manuscripts for publication in international peer-reviewed scientific journals.

TRIAL REGISTRATION NUMBER:

2020-001544-26; NCT04351581.

• Authors: Vivian Kliim-Hansen, Lærke Smidt Gasbjerg, Anne-Marie Ellegaard, Hans Johan Niklas Lorentsson, Mads Bank Lynggaard, Christoffer Andersen Hagemann, Christian Legart, David Siersbæk Mathiesen, Pradeesh Sivapalan, Jens-Ulrik Stæhr Jensen, Tina Vilsbøll, Mikkel Bring Christensen, Filip Krag Knop
• Journal: BMJ open (BMJ Open) Vol. 12 Issue 11 Pg. e062895 (11 30 2022) ISSN: 2044-6055 [Electronic] England
• PMID: 36450422 (Publication Type: Clinical Trial Protocol, Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.

Chemical References

• Angiotensin Receptor Antagonists
• Angiotensin-Converting Enzyme Inhibitors
• Antihypertensive Agents
• Enzyme Inhibitors

Topics

• Humans
• Renin-Angiotensin System
• Angiotensin Receptor Antagonists (therapeutic use)
• Angiotensin-Converting Enzyme Inhibitors (therapeutic use)
• Pandemics
• Antihypertensive Agents
• Enzyme Inhibitors
• Randomized Controlled Trials as Topic
• COVID-19 Drug Treatment