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

Sonali Rukshana Gnanenthiran; Claudio Borghi; Dylan Burger; Fadi Charchar; Neil R Poulter; Markus P Schlaich; Ulrike Muscha Steckelings; George Stergiou; Maciej Tomaszewski; Thomas Unger; Richard D Wainford; Bryan Williams; Anthony Rodgers; Aletta E Schutte

doi:10.1136/bmjopen-2020-043625

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. 2021 Feb 16;11(2):e043625. doi: 10.1136/bmjopen-2020-043625.

Authors

Affiliations

¹ The George Institute for Global Health; University of New South Wales, Sydney, New South Wales, Australia.
² Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy.
³ Department of Cellular and Molecular Medicine, Kidney Research Centre, Ottawa Hospital Research Institute, University of Ottawa, Ottawa, Ontario, Canada.
⁴ School of Health and Life Sciences, Federation University Australia, Ballarat, Victoria, Australia.
⁵ Imperial Clinical Trials Unit, Imperial College London, London, UK.
⁶ Dobney Hypertension Centre, School of Medicine, Royal Perth Hospital Unit, University of Western Australia, Perth, Western Australia, Australia.
⁷ Department of Cardiovascular and Renal Research, University of Southern Denmark, Odense, Denmark.
⁸ Third Department of Medicine, Hypertension Center STRIDE-7, School of Medicine, Sotiria Hospital, National and Kapodistrian University of Athens, Athens, Greece.
⁹ Division of Medicine and Manchester Academic Health Science Centre, Manchester University NHS Foundation Trust Manchester, Manchester, UK.
¹⁰ CARIM-School for Cardiovascular Diseases, Maastricht University, Maastricht, The Netherlands.
¹¹ Department of Pharmacology and Experimental Therapeutics and the Whitaker Cardiovascular Institute, Boston University School of Medicine, Boston, Massachusetts, USA.
¹² Institute of Cardiovascular Science, University College London and National Institute for Health Research (NIHR) University College London Hospitals Biomedical Research Centre, London, UK.
¹³ The George Institute for Global Health; University of New South Wales, Sydney, New South Wales, Australia a.schutte@unsw.edu.au.

Abstract

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.

Keywords: COVID-19; cardiology; hypertension.

MeSH terms

Angiotensin Receptor Antagonists / therapeutic use*
Angiotensin-Converting Enzyme Inhibitors / therapeutic use*
COVID-19 Drug Treatment*
Humans
Meta-Analysis as Topic*
Prospective Studies
Randomized Controlled Trials as Topic
Renin-Angiotensin System
Research Design

Substances

Angiotensin Receptor Antagonists
Angiotensin-Converting Enzyme Inhibitors