Drug repurposing for COVID-19: current evidence from randomized controlled adaptive platform trials and living systematic reviews.

Publisher: Oxford University Press Country of Publication: England NLM ID: 0376542 Publication Model: Print Cited Medium: Internet ISSN: 1471-8391 (Electronic) Linking ISSN: 00071420 NLM ISO Abbreviation: Br Med Bull Subsets: MEDLINE

Publication: 2001- : London : Oxford University Press
Original Publication: London.

COVID-19*; Aged ; Humans ; Adrenal Cortex Hormones ; Antiviral Agents/therapeutic use ; Drug Repositioning ; Imatinib Mesylate ; Randomized Controlled Trials as Topic ; Systematic Reviews as Topic

Introduction: The coronavirus disease 2019 (COVID-19) pandemic resulted in a race to develop effective treatments largely through drug repurposing via adaptive platform trials on a global scale. Drug repurposing trials have focused on potential antiviral therapies aimed at preventing viral replication, anti-inflammatory agents, antithrombotic agents and immune modulators through a number of adaptive platform trials. Living systematic reviews have also enabled evidence synthesis and network meta-analysis as clinical trial data emerge globally.
Sources of Data: Recent published literature.
Areas of Agreement: Corticosteroids and immunomodulators that antagonize the interleukin-6 (IL-6) receptor have been shown to play a critical role in modulating inflammation and improving clinical outcomes in hospitalized patients. Inhaled budesonide reduces the time to recovery in older patients with mild-to-moderate COVID-19 managed in the community.
Areas of Controversy: The clinical benefit of remdesivir remains controversial with conflicting evidence from different trials. Remdesivir led to a reduction in time to clinical recovery in the ACTT-1 trial. However, the World Health Organization SOLIDARITY and DISCOVERY trial did not find a significant benefit on 28-day mortality and clinical recovery.
Growing Points: Other treatments currently being investigated include antidiabetic drug empagliflozin, antimalarial drug artesunate, tyrosine kinase inhibitor imatinib, immunomodulatory drug infliximab, antiviral drug favipiravir, antiparasitic drug ivermectin and antidepressant drug fluvoxamine.
Areas Timely for Developing Research: The timing of therapeutic interventions based on postulated mechanisms of action and the selection of clinically meaningful primary end points remain important considerations in the design and implementation of COVID-19 therapeutic trials.
(© The Author(s) 2022. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

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United Kingdom WT_ Wellcome Trust; 204809/Z/16/Z United Kingdom WT_ Wellcome Trust

Keywords: COVID-19; adaptive platform trials; drug repurposing

0 (Adrenal Cortex Hormones)
0 (Antiviral Agents)
8A1O1M485B (Imatinib Mesylate)

Date Created: 20230614 Date Completed: 20230919 Latest Revision: 20240614

20240614

PMC10502446

10.1093/bmb/ldac037

37312588