FLARE: Favipiravir +/- Lopinavir: A RCT of Early Antivirals
FLARE
Favipiravir, Lopinavir/Ritonavir or Combination Therapy: a Randomised, Double Blind, 2x2 Factorial Placebo-controlled Trial of Early Antiviral Therapy in COVID-19
1 other identifier
interventional
240
1 country
2
Brief 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. Antiviral medications are most likely to be effective when administered soon after infection. There is therefore an urgent need to study subjects who have recently developed symptoms, or have recently been tested positive with or without symptoms, and who can be sampled frequently to understand changes in viral load. This cohort will allow us to collect detailed trajectory data on early disease and understand how pharmacological interventions may affect this. 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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_2 covid19
Started Sep 2020
Typical duration for phase_2 covid19
2 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
June 16, 2020
CompletedFirst Posted
Study publicly available on registry
August 5, 2020
CompletedStudy Start
First participant enrolled
September 24, 2020
CompletedPrimary Completion
Last participant's last visit for primary outcome
December 1, 2021
CompletedStudy Completion
Last participant's last visit for all outcomes
January 17, 2022
CompletedDecember 15, 2022
December 1, 2021
1.2 years
June 16, 2020
December 12, 2022
Conditions
Outcome Measures
Primary Outcomes (1)
Upper respiratory tract viral load at Day 5
Quantitative polymerase chain reaction (PCR) performed on saliva samples at Day 5 of therapy
Day 5 from randomisation
Secondary Outcomes (20)
Percentage of participants with undetectable upper respiratory tract viral load after 5 days of therapy
5 days from randomisation
Proportion of participants with undetectable stool viral load after 7 days of therapy.
7 days from randomisation
Rate of decrease in upper respiratory tract viral load during 7 days of therapy
7 days
Duration of fever following commencement of medication
7 days
Proportion of participants with hepatotoxicity after 7 days of therapy
7 days from randomisation
- +15 more secondary outcomes
Study Arms (4)
Favipiravir + Lopinavir/ritonavir (LPV/r)
EXPERIMENTALOral favipiravir at 1800 mg twice daily on Day 1, followed by 400 mg four (4) times daily from Day 2 to Day 7 PLUS Lopinavir/ritonavir (LPV/r) at 400mg/100 mg twice daily on Day 1, followed by 200mg/50mg four (4) times daily from Day 2 to Day 7
Favipiravir + Lopinavir/ritonavir (LPV/r) placebo
EXPERIMENTALOral favipiravir at 1800 mg twice daily on Day 1, followed by 400 mg four (4) times daily from Day 2 to Day 7 PLUS Lopinavir/ritonavir (LPV/r) matched placebo at 400mg/100mg twice daily on Day 1, followed by 200mg/50mg four (4) times daily from Day 2 to Day 7.
Favipiravir placebo + Lopinavir/ritonavir (LPV/r)
EXPERIMENTALOral favipiravir matched placebo at 1800 mg twice daily on Day 1, by 400 mg four (4) times daily from Day 2 to Day 7 PLUS Lopinavir/ritonavir (LPV/r) at 400mg/100mg twice daily on Day 1, followed by 200mg/50mg four (4) times daily from Day 2 to Day 7.
Favipiravir placebo + Lopinavir/ritonavir (LPV/r) placebo
PLACEBO COMPARATOROral favipiravir matched placebo at 1800 mg twice daily on Day 1, by 400 mg four (4) times daily from Day 2 to Day 7 PLUS Lopinavir/ritonavir (LPV/r) matched placebo at 400mg/100mg twice daily on Day 1, followed by 200mg/50mg four (4) times daily from Day 2 to Day 7.
Interventions
Dosage and method of administration: Day 1: 1800 mg twice daily; Day 2 to Day 7: 400 mg four (4) times daily.
Dosage and method of administration: Day 1: 400mg/100 mg twice daily; Day 2 to Day 7: 200mg/50mg four (4) times daily
Dosage and method of administration: Day 1: 1800 mg twice daily; Day 2 to Day 7: 400 mg four (4) times daily.
Dosage and method of administration: Day 1: 1800 mg twice daily; Day 2 to Day 7: 400 mg four (4) times daily.
Eligibility Criteria
You may qualify if:
- Any adult with the following:
- Symptoms compatible with COVID-19 disease (Fever \>37.8oC on at least one occasion AND either cough and/ or anosmia) within the first 5 days of symptom onset
- OR ANY symptoms compatible with COVID-19 disease (may include, but are not limited to fever, cough, shortness of breath, malaise, myalgia, headache, coryza) and tested positive for SARS-CoV-2 within the first 7 days of symptom onset
- OR no symptoms but tested positive for SARS-CoV-2 within the last 48 hours (date/time of test must be within 48 hours of enrolment)
- Male or female aged 18 years to 70 years old inclusive at screening
- Willing and able to take daily saliva samples
- Able to provide full informed consent and willing to comply with trial-related procedures
You may not qualify if:
- Known hypersensitivity to any of the active ingredients or excipients in favipiravir and matched placebo, and in lopinavir/ritonavir and matched placebo
- Chronic liver disease at screening (known cirrhosis of any aetiology, chronic hepatitis (e.g. autoimmune, viral, steatohepatitis), cholangitis or any known elevation of liver aminotransferases with AST or ALT \> 3 X ULN)\*
- Chronic kidney disease (stage 3 or beyond) at screening: eGFR \< 60 ml/min/1.73m2\*
- HIV infection, if untreated, detectable viral load or on protease inhibitor therapy
- Any clinical condition which the investigator considers would make the participant unsuitable for the trial
- Concomitant medications known to interact with favipiravir and matched placebo, and with lopinavir/ritonavir and matched placebo, and carry risk of toxicity for the participant
- Current severe illness requiring hospitalisation
- Pregnancy and/ or breastfeeding
- Eligible female participants of childbearing potential and male participants with a partner of childbearing potential not willing to use highly effective contraceptive measures during the trial and within the time point specified following last trial treatment dose.
- Participants enrolled in any other interventional drug or vaccine trial (co-enrolment in observational studies is acceptable).
- Considering the importance of early treatment of COVID-19 to impact viral load, the absence of chronic liver/ kidney disease will be confirmed verbally by the participant during pre-screening and Screening/Baseline visit. Safety blood samples will be collected at Screening/Baseline visit (Day 1) and test results will be examined as soon as they become available within 24 hours.
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- University College, Londonlead
- LifeArccollaborator
Study Sites (2)
Royal Free Hospital
London, NW3 2QG, United Kingdom
University College London Hospital (UCLH)
London, United Kingdom
Related Publications (2)
Lowe DM, Brown LK, Chowdhury K, Davey S, Yee P, Ikeji F, Ndoutoumou A, Shah D, Lennon A, Rai A, Agyeman AA, Checkley A, Longley N, Dehbi HM, Freemantle N, Breuer J, Standing JF; FLARE Investigators. Favipiravir, lopinavir-ritonavir, or combination therapy (FLARE): A randomised, double-blind, 2 x 2 factorial placebo-controlled trial of early antiviral therapy in COVID-19. PLoS Med. 2022 Oct 19;19(10):e1004120. doi: 10.1371/journal.pmed.1004120. eCollection 2022 Oct.
PMID: 36260627DERIVEDBrown LK, Freemantle N, Breuer J, Dehbi HM, Chowdhury K, Jones G, Ikeji F, Ndoutoumou A, Santhirakumar K, Longley N, Checkley AM, Standing JF, Lowe DM. Early antiviral treatment in outpatients with COVID-19 (FLARE): a structured summary of a study protocol for a randomised controlled trial. Trials. 2021 Mar 8;22(1):193. doi: 10.1186/s13063-021-05139-2.
PMID: 33685502DERIVED
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
David Lowe
Institute of Immunity and Transplantation, University College London
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- RANDOMIZED
- Masking
- TRIPLE
- Who Masked
- PARTICIPANT, CARE PROVIDER, INVESTIGATOR
- Masking Details
- Double-blind
- Purpose
- TREATMENT
- Intervention Model
- FACTORIAL
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
June 16, 2020
First Posted
August 5, 2020
Study Start
September 24, 2020
Primary Completion
December 1, 2021
Study Completion
January 17, 2022
Last Updated
December 15, 2022
Record last verified: 2021-12
Data Sharing
- IPD Sharing
- Will not share
No plan to share IPD has been made at this time.