FLARE [COVID-19]
Research type
Research Study
Full title
Favipiravir, lopinavir/ritonavir or combination therapy: a randomised, double blind, 2x2 factorial placebo-controlled trial of early antiviral therapy in COVID-19
IRAS ID
284664
Contact name
David Lowe
Contact email
Sponsor organisation
University College London Comprehensive Clinical Trial Unit
Eudract number
2020-002106-68
Duration of Study in the UK
0 years, 9 months, 0 days
Research summary
Research Summary
The current pandemic of SARS-CoV-2 causing COVID-19 disease is an unprecedented global emergency. COVID-19 appears to be a disease with an early phase where the virus replicates, coinciding with first presentation of symptoms, followed by a later ’inflammatory’ phase which results in severe disease in some individuals. It is known from other rapidly progressive infections such as sepsis and influenza that early treatment with antimicrobials is associated with better outcome. The trial will be conducted in key workers who are at high risk of acquiring SARS-CoV-2 infection and their household members. Apart from the risk of severe illness and death in the workers themselves and their household members, this phenomenon also impacts health system staffing levels. The objective of the FLARE trial is to assess whether early antiviral therapy with either favipiravir + Lopinavir/ritonavir (LPV/r), LPV/r or favipiravir is associated with a decrease in viral load compared with placebo.The hypothesis is that this holds for COVID-19 and that early antiviral treatment may prevent progression to the later phase of the disease.
Summary of Results
The FLARE trial aimed to discover whether existing oral antiviral drugs (Favipiravir, lopinavir/ritonavir) could reduce the viral load of the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) virus if given soon after symptoms started. Participants (aged 18 years to 70 years old inclusive) received favipiravir plus lopinavir-ritonavir, favipiravir plus lopinavir-ritonavir placebo, favipiravir placebo plus lopinavir-ritonavir, or placebos ('dummy') of both drugs. Favipiravir or matched placebo was administered at a dose of 1,800 mg twice daily on Day 1, followed by 400 mg 4 times daily from Day 2 to Day 7. Lopinavir-ritonavir or matched placebo were given at a dose of 400 mg/100 mg twice daily on Day 1, followed by 200 mg/50 mg 4 times daily from Day 2 to Day 7. Participants were advised to take both Day 1 doses on the first day regardless of time of enrolment, due to the perceived importance of achieving high antiviral levels as early as possible.
The major finding of the FLARE trial is that, at the doses used, there is no clear evidence that either favipiravir monotherapy, lopinavir-ritonavir monotherapy, or favipiravir plus lopinavir-ritonavir produce clinically worthwhile reductions in viral load in early treatment. FLARE provides insufficient evidence to take these therapies into Phase 3. However, further study of favipiravir may be warranted, in particular, dose escalation studies might identify more efficacious doses against SARS-CoV-2.REC name
Wales REC 3
REC reference
20/WA/0210
Date of REC Opinion
16 Jul 2020
REC opinion
Further Information Favourable Opinion