TY - JOUR
T1 - 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
T2 - the RASCOVID-19 trial
AU - Kliim-Hansen, Vivian
AU - Gasbjerg, Lærke Smidt
AU - Ellegaard, Anne-Marie
AU - Lorentsson, Hans Johan Niklas
AU - Lynggaard, Mads Bank
AU - Hagemann, Christoffer Andersen
AU - Legart, Christian
AU - Mathiesen, David Siersbæk
AU - Sivapalan, Pradeesh
AU - Jensen, Jens-Ulrik Stæhr
AU - Vilsbøll, Tina
AU - Christensen, Mikkel Bring
AU - Knop, Filip Krag
N1 - © 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.
PY - 2022/11/30
Y1 - 2022/11/30
N2 - 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.
AB - 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.
KW - Humans
KW - COVID-19/drug therapy
KW - Renin-Angiotensin System
KW - Angiotensin Receptor Antagonists/therapeutic use
KW - Angiotensin-Converting Enzyme Inhibitors/therapeutic use
KW - Pandemics
KW - Antihypertensive Agents
KW - Enzyme Inhibitors
KW - Randomized Controlled Trials as Topic
KW - COVID-19
KW - hypertension
KW - general medicine (see internal medicine)
UR - http://www.scopus.com/inward/record.url?scp=85143092675&partnerID=8YFLogxK
U2 - 10.1136/bmjopen-2022-062895
DO - 10.1136/bmjopen-2022-062895
M3 - Journal article
C2 - 36450422
SN - 2399-9772
VL - 12
SP - e062895
JO - BMJ Paediatrics Open
JF - BMJ Paediatrics Open
IS - 11
M1 - e062895
ER -