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.

Autor:	Kliim-Hansen V; Center for Clinical Metabolic Research, Department of Medicine, Copenhagen University Hospital - Herlev and Gentofte, Hellerup, Denmark., Gasbjerg LS; Center for Clinical Metabolic Research, Department of Medicine, Copenhagen University Hospital - Herlev and Gentofte, Hellerup, Denmark.; Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark., Ellegaard AM; Center for Clinical Metabolic Research, Department of Medicine, Copenhagen University Hospital - Herlev and Gentofte, Hellerup, Denmark., Lorentsson HJN; Center for Clinical Metabolic Research, Department of Medicine, Copenhagen University Hospital - Herlev and Gentofte, Hellerup, Denmark.; Section of Infectious Medicine, Department of Medicine, Copenhagen University Hospital - Herlev and Gentofte, Hellerup, Denmark.; Clinical Research, Steno Diabetes Center Copenhagen, Herlev, Denmark., Lynggaard MB; Center for Clinical Metabolic Research, Department of Medicine, Copenhagen University Hospital - Herlev and Gentofte, Hellerup, Denmark., Hagemann CA; Center for Clinical Metabolic Research, Department of Medicine, Copenhagen University Hospital - Herlev and Gentofte, Hellerup, Denmark.; Gubra Aps, Hoersholm, Denmark., Legart C; Center for Clinical Metabolic Research, Department of Medicine, Copenhagen University Hospital - Herlev and Gentofte, Hellerup, Denmark., Mathiesen DS; Center for Clinical Metabolic Research, Department of Medicine, Copenhagen University Hospital - Herlev and Gentofte, Hellerup, Denmark., Sivapalan P; Section of Respiratory Medicine, Department of Medicine, Copenhagen University Hospital - Herlev and Gentofte, Hellerup, Denmark., Jensen JS; Section of Respiratory Medicine, Department of Medicine, Copenhagen University Hospital - Herlev and Gentofte, Hellerup, Denmark.; Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark., Vilsbøll T; Center for Clinical Metabolic Research, Department of Medicine, Copenhagen University Hospital - Herlev and Gentofte, Hellerup, Denmark.; Clinical Research, Steno Diabetes Center Copenhagen, Herlev, Denmark., Christensen MB; Center for Clinical Metabolic Research, Department of Medicine, Copenhagen University Hospital - Herlev and Gentofte, Hellerup, Denmark.; Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.; Department of Clinical Pharmacology, Bispebjerg and Frederiksberg Hospital, University of Copenhagen, Faculty of Health and Medical Sciences, Copenhagen, Denmark.; Copenhagen Center for Translational Research, Copenhagen University Hospital - Bispebjerg and Frederiksberg Hospital, Copenhagen, Denmark., Knop FK; Center for Clinical Metabolic Research, Department of Medicine, Copenhagen University Hospital - Herlev and Gentofte, Hellerup, Denmark filip.krag.knop.01@regionh.dk.; Clinical Research, Steno Diabetes Center Copenhagen, Herlev, Denmark.; Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.; Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty og Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
Jazyk:	angličtina
Zdroj:	BMJ open [BMJ Open] 2022 Nov 30; Vol. 12 (11), pp. e062895. Date of Electronic Publication: 2022 Nov 30.
DOI:	10.1136/bmjopen-2022-062895
Abstrakt:	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. Competing Interests: Competing interests: None declared. (© 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.)
Databáze:	MEDLINE
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