Combination therapies for COVID-19: An overview of the clinical trials landscape

Sola Akinbolade*, Diarmuid Coughlan, Ross Fairbairn, Glenn McConkey, Helen Powell, Dapo Ogunbayo, Dawn Craig

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review


The COVID-19 pandemic has driven an unprecedented level of global activity in drug discovery and clinical development for effective therapeutics targeting the coronavirus disease. There are currently 744 therapeutics being tested in 2879 clinical trials globally. Almost 90% of these clinical trials are focused on monotherapies. Combination therapies are the mainstay of antiviral therapeutics to increase the potency of the individual compounds and to combat the rapid evolution of resistance, although combination therapies have inherently complex clinical and regulatory development challenges. Increased understanding of the SARS-CoV-2 lifecycle and COVID-19 pathology provides a scientific rationale for evaluating the effectiveness of different combinations. In this paper, we provide an overview of the current clinical trial landscape for combination therapeutics targeting COVID-19 through weekly scanning of national and international clinical trial registries. Our analysis delves specifically into dual combination therapies in what can be defined as “pivotal clinical trials” (active, randomised, controlled and at least phase II), with a focus on new and repurposed therapeutic candidates that have shown positive signals and/or been granted authorisation for emergency use based on positive efficacy and safety data.

Original languageEnglish
Pages (from-to)1590-1597
Number of pages8
JournalBritish Journal of Clinical Pharmacology
Issue number4
Early online date17 Oct 2021
Publication statusPublished - 1 Apr 2022

Bibliographical note

Funding Information:
This project is funded by the NIHR (HSRIC‐2016‐10 009)/Innovation Observatory. The views expressed are those of the author(s) and not necessarily those of the NIHR or the Department of Health and Social Care.

Publisher Copyright:
© 2021 British Pharmacological Society.


  • clinical trials
  • combination therapy
  • COVID-19
  • pivotal trials
  • SARS-CoV-2
  • treatment

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