Accelerating Clinical Evaluation of Repurposed Combination Therapies for COVID-19

Am J Trop Med Hyg. 2020 Oct;103(4):1364-1366. doi: 10.4269/ajtmh.20-0995.


As the global COVID-19 pandemic continues, unabated and clinical trials demonstrate limited effective pharmaceutical interventions, there is a pressing need to accelerate treatment evaluations. Among options for accelerated development is the evaluation of drug combinations in the absence of prior monotherapy data. This approach is appealing for a number of reasons. First, combining two or more drugs with related or complementary therapeutic effects permits a multipronged approach addressing the variable pathways of the disease. Second, if an individual component of a combination offers a therapeutic effect, then in the absence of antagonism, a trial of combination therapy should still detect individual efficacy. Third, this strategy is time saving. Rather than taking a stepwise approach to evaluating monotherapies, this strategy begins with testing all relevant therapeutic options. Finally, given the severity of the current pandemic and the absence of treatment options, the likelihood of detecting a treatment effect with combination therapy maintains scientific enthusiasm for evaluating repurposed treatments. Antiviral combination selection can be facilitated by insights regarding SARS-CoV-2 pathophysiology and cell cycle dynamics, supported by infectious disease and clinical pharmacology expert advice. We describe a clinical evaluation strategy using adaptive combination platform trials to rapidly test combination therapies to treat COVID-19.

MeSH terms

  • Antiviral Agents / therapeutic use*
  • Betacoronavirus / drug effects
  • Betacoronavirus / immunology
  • Betacoronavirus / pathogenicity
  • COVID-19
  • Clinical Trials as Topic
  • Coronavirus Infections / drug therapy*
  • Coronavirus Infections / epidemiology*
  • Coronavirus Infections / immunology
  • Coronavirus Infections / virology
  • Drug Combinations
  • Drug Repositioning / methods
  • Drug Therapy, Combination / methods*
  • Epidemiologic Research Design*
  • Humans
  • Interferon beta-1b / therapeutic use
  • Lopinavir / therapeutic use
  • Pandemics*
  • Pneumonia, Viral / drug therapy*
  • Pneumonia, Viral / epidemiology*
  • Pneumonia, Viral / immunology
  • Pneumonia, Viral / virology
  • Ribavirin / therapeutic use
  • Ritonavir / therapeutic use
  • SARS-CoV-2


  • Antiviral Agents
  • Drug Combinations
  • lopinavir-ritonavir drug combination
  • Interferon beta-1b
  • Lopinavir
  • Ribavirin
  • Ritonavir