Prospective meta-analysis protocol on randomised trials of renin–angiotensin system inhibitors in patients with COVID-19: an initiative of the International Society of Hypertension

Introduction Whether ACE inhibitors (ACEi) or angiotensin II receptor blocker (ARB) therapy should be continued, initiated or ceased in patients with COVID-19 is uncertain. Given the widespread use of ACEi/ARBs worldwide, guidance on the use of these drugs is urgently needed. This prospective meta-a...

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Main Authors: Anthony Rodgers, George Stergiou, Bryan Williams, Sonali Rukshana Gnanenthiran, Markus P Schlaich, Claudio Borghi, Dylan Burger, Fadi Charchar, Neil R Poulter, Ulrike Muscha Steckelings, Maciej Tomaszewski, Thomas Unger, Richard D Wainford, Aletta E Schutte
Format: Article
Language:English
Published: BMJ Publishing Group 2021-02-01
Series:BMJ Open
Online Access:https://bmjopen.bmj.com/content/11/2/e043625.full
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author Anthony Rodgers
George Stergiou
Bryan Williams
Sonali Rukshana Gnanenthiran
Markus P Schlaich
Claudio Borghi
Dylan Burger
Fadi Charchar
Neil R Poulter
Ulrike Muscha Steckelings
Maciej Tomaszewski
Thomas Unger
Richard D Wainford
Aletta E Schutte
author_facet Anthony Rodgers
George Stergiou
Bryan Williams
Sonali Rukshana Gnanenthiran
Markus P Schlaich
Claudio Borghi
Dylan Burger
Fadi Charchar
Neil R Poulter
Ulrike Muscha Steckelings
Maciej Tomaszewski
Thomas Unger
Richard D Wainford
Aletta E Schutte
author_sort Anthony Rodgers
collection DOAJ
description Introduction Whether ACE inhibitors (ACEi) or angiotensin II receptor blocker (ARB) therapy should be continued, initiated or ceased in patients with COVID-19 is uncertain. Given the widespread use of ACEi/ARBs worldwide, guidance on the use of these drugs is urgently needed. This prospective meta-analysis aims to pool data from randomised controlled trials (RCTs) to assess the safety and efficacy of ACEi/ARB therapy in adults infected with SARS-CoV-2.Methods and analysis RCTs will be eligible if they compare patients with COVID-19 randomised to ACEi/ARB continuation or commencement versuss no ACEi/ARB therapy; study duration ≥14 days; recruitment completed between March 2020 and May 2021. The primary outcome will be all-cause mortality at ≤30 days. Secondary outcomes will include mechanical ventilation, admission to intensive care or cardiovascular events at short-term follow-up (≤30 days) and all-cause mortality at longer-term follow-up (>1 month). Prespecified subgroup analyses will assess the effect of sex; age; comorbidities; smoking status; ethnicity; country of origin on all-cause mortality. A search of ClinicalTrials.gov has been performed, which will be followed by a formal search of trial registers, preprint servers, MEDLINE, EMBASE and Cochrane Central Register of Controlled Trials to identify RCTs that meet inclusion criteria. To date, a search of ClinicalTrials.gov identified 21 potentially eligible trials for this meta-analysis. We will request trial investigators/sponsors to contribute standardised grouped tabular outcome data.Ethics and dissemination Ethics approval and informed consent will be the responsibility of the individual RCTs. Dissemination of results will occur by peer-reviewed publication. The results of our analysis can inform public health policy and clinical decision making regarding ACEi/ARB use in patients with COVID-19 on a global scale.
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spelling doaj-art-5ed6eafb09d144878bd26b19183d0b0d2024-11-17T08:20:10ZengBMJ Publishing GroupBMJ Open2044-60552021-02-0111210.1136/bmjopen-2020-043625Prospective meta-analysis protocol on randomised trials of renin–angiotensin system inhibitors in patients with COVID-19: an initiative of the International Society of HypertensionAnthony Rodgers0George Stergiou1Bryan Williams2Sonali Rukshana Gnanenthiran3Markus P Schlaich4Claudio Borghi5Dylan Burger6Fadi Charchar7Neil R Poulter8Ulrike Muscha Steckelings9Maciej Tomaszewski10Thomas Unger11Richard D Wainford12Aletta E Schutte13The George Institute for Global Health; University of New South Wales, Sydney, New South Wales, Australia39 School of Medicine, Hypertension Center STRIDE-7, National and Kapodistrian University of Athens, Athens, GreeceNIHR University College London Hospitals Biomedical Research Centre, London, UK1 Cardiology Department, Concord Repatriation General Hospital University of Sydney, Sydney, New South Wales, AustraliaDobney Hypertension Centre, School of Medicine, Royal Perth Hospital Unit, University of Western Australia, Perth, Western Australia, Australia1 Azienda Ospedaliero-Universitaria di Bologna IRCCS, Bologna, Emilia-Romagna, ItalyDepartment of Cellular and Molecular Medicine, Kidney Research Centre, Ottawa Hospital Research Institute, University of Ottawa, Ottawa, Ontario, CanadaSchool of Health and Life Sciences, Federation University Australia, Ballarat, Victoria, AustraliaImperial Clinical Trials Unit, Imperial College London, London, UKDepartment of Cardiovascular and Renal Research, University of Southern Denmark, Odense, Denmark3University of ManchesterCARIM–School for Cardiovascular Diseases, Maastricht University, Maastricht, The NetherlandsDepartment of Pharmacology and Experimental Therapeutics and the Whitaker Cardiovascular Institute, Boston University School of Medicine, Boston, Massachusetts, USASchool of Population Health, University of New South Wales, Sydney, New South Wales, AustraliaIntroduction Whether ACE inhibitors (ACEi) or angiotensin II receptor blocker (ARB) therapy should be continued, initiated or ceased in patients with COVID-19 is uncertain. Given the widespread use of ACEi/ARBs worldwide, guidance on the use of these drugs is urgently needed. This prospective meta-analysis aims to pool data from randomised controlled trials (RCTs) to assess the safety and efficacy of ACEi/ARB therapy in adults infected with SARS-CoV-2.Methods and analysis RCTs will be eligible if they compare patients with COVID-19 randomised to ACEi/ARB continuation or commencement versuss no ACEi/ARB therapy; study duration ≥14 days; recruitment completed between March 2020 and May 2021. The primary outcome will be all-cause mortality at ≤30 days. Secondary outcomes will include mechanical ventilation, admission to intensive care or cardiovascular events at short-term follow-up (≤30 days) and all-cause mortality at longer-term follow-up (>1 month). Prespecified subgroup analyses will assess the effect of sex; age; comorbidities; smoking status; ethnicity; country of origin on all-cause mortality. A search of ClinicalTrials.gov has been performed, which will be followed by a formal search of trial registers, preprint servers, MEDLINE, EMBASE and Cochrane Central Register of Controlled Trials to identify RCTs that meet inclusion criteria. To date, a search of ClinicalTrials.gov identified 21 potentially eligible trials for this meta-analysis. We will request trial investigators/sponsors to contribute standardised grouped tabular outcome data.Ethics and dissemination Ethics approval and informed consent will be the responsibility of the individual RCTs. Dissemination of results will occur by peer-reviewed publication. The results of our analysis can inform public health policy and clinical decision making regarding ACEi/ARB use in patients with COVID-19 on a global scale.https://bmjopen.bmj.com/content/11/2/e043625.full
spellingShingle Anthony Rodgers
George Stergiou
Bryan Williams
Sonali Rukshana Gnanenthiran
Markus P Schlaich
Claudio Borghi
Dylan Burger
Fadi Charchar
Neil R Poulter
Ulrike Muscha Steckelings
Maciej Tomaszewski
Thomas Unger
Richard D Wainford
Aletta E Schutte
Prospective meta-analysis protocol on randomised trials of renin–angiotensin system inhibitors in patients with COVID-19: an initiative of the International Society of Hypertension
BMJ Open
title Prospective meta-analysis protocol on randomised trials of renin–angiotensin system inhibitors in patients with COVID-19: an initiative of the International Society of Hypertension
title_full Prospective meta-analysis protocol on randomised trials of renin–angiotensin system inhibitors in patients with COVID-19: an initiative of the International Society of Hypertension
title_fullStr Prospective meta-analysis protocol on randomised trials of renin–angiotensin system inhibitors in patients with COVID-19: an initiative of the International Society of Hypertension
title_full_unstemmed Prospective meta-analysis protocol on randomised trials of renin–angiotensin system inhibitors in patients with COVID-19: an initiative of the International Society of Hypertension
title_short Prospective meta-analysis protocol on randomised trials of renin–angiotensin system inhibitors in patients with COVID-19: an initiative of the International Society of Hypertension
title_sort prospective meta analysis protocol on randomised trials of renin angiotensin system inhibitors in patients with covid 19 an initiative of the international society of hypertension
url https://bmjopen.bmj.com/content/11/2/e043625.full
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