Clinical trial to investigate the early intervention of mild COVID-19 in healthcare workers with broad-spectrum antivirals

Research title

Favipiravir, lopinavir/ritonavir or combination therapy: a randomised, double blind, 2×2 factorial placebo-controlled trial of early antiviral therapy in COVID-19 (the FLARE trial)


University College London (UCL), with funding from LifeArc, is set to conduct a placebo-controlled clinical trial to determine if early treatment with antiviral drugs favipiravir and lopinavir/ritonavir prevents the progression of COVID-19 in healthcare workers who have experienced symptoms for less than 3 days. Favipiravir, as a single therapeutic, has demonstrated early signs that is might offer potential clinical benefit in COVID-19 and both drugs have the potential to inhibit replication of SARS-CoV-2. This UCL study aims to investigate the effect of favipiravir, lopinavir/ritonavir or the combination of both drugs on reducing viral load.

Research organisation

University College London


Principal Investigator:

  • Dr David Lowe, University College London


  • Prof Judith Breuer, University College London
  • Prof Nick Freemantle, University College London
  • Dr Joseph Standing, University College London
  • Dr Hakim-Moulay Dehbi, University College London
  • Gemma Jones, University College London

Potential of repurposed therapeutic for COVID-19 pandemic

COVID-19 is thought to be a disease which in its early phase, when symptoms first present in patients, sees the virus replicate significantly. This is followed by an inflammatory phase which can result in severe damage to the lungs, a common deadly symptom seen in severe cases of COVID-19. The researchers hypothesise that giving effective early antiviral therapy will help to prevent progression to this second phase.

Favipiravir is a broad-spectrum antiviral, which acts against a wide range of RNA viruses through its inhibition of RNA polymerase, an enzyme vital for viral replication. Favipiravir is approved for treatment of influenza in Japan. Lopinavir/ritonavir (LPV/r) is an antiviral protease inhibitor and is widely used as a drug for treatment of HIV. In the laboratory, both drugs individually have demonstrated the ability to inhibit viral replication of the coronavirus responsible for COVID-19 and they act at sequential steps of the viral replication pathway.

However, researchers at UCL aim to investigate the relative antiviral effects of favipiravir and LPV/r against COVID-19 in a clinical trial by testing each drug as a monotherapy and in combination with each other. The combination therapy might have a greater impact in reducing the replication of the virus than treatment with each drug as a monotherapy. If successful, this early treatment method would help reduce the risk of COVID-19 on healthcare workers and negate the significant impact the virus has had on the health systems staffing levels. Researchers would also then plan to investigate this strategy of early antiviral treatment in high-risk patients to prevent serious outcomes from the disease including hospitalisation and death.

The clinical trial will take place at Royal Free London NHS Foundation Trust, University College London Hospitals NHS Foundation Trust and Great Ormond Street Hospital NHS Foundation Trust. The MHRA have been alerted of the study and rapid set-up of the trial is anticipated. The trial is hoped to be complete in three months but a total of nine has been allowed for logistics and data analysis.

FujiFilm Toyama Chemical Co. has agreed to supply favipiravir and the placebo free of charge for the trial.