COVID-19Phase 2FLARENCT04499677
FLARE: Favipiravir +/- Lopinavir: A RCT of Early Antivirals
A Phase 2 study testing Favipiravir and Lopinavir/ Ritonavir in people with COVID-19, run by University College, London at 2 sites in United Kingdom.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- COVID-19
- What is being tested?
- Favipiravir and Lopinavir/ Ritonavir
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 240 participants
- Where
- 2 sitesUnited Kingdom
- Study dates
- 24 Sep 2020to 17 Jan 2022
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Show all 11Show fewer
- 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.
Trial locations and contacts
2 sites in 1 country.
United Kingdom2 sites
Royal Free Hospital
London, NW3 2QG
University College London Hospital (UCLH)
London
About this study
Official title: Favipiravir, Lopinavir/Ritonavir or Combination Therapy: a Randomised, Double Blind, 2x2 Factorial Placebo-controlled Trial of Early Antiviral Therapy in COVID-19
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.
Read the detailed description
FLARE is a phase IIA randomised, double-blind, 2x2 factorial placebo-controlled, interventional trial in which 240 participants, aged 18 years (≥ 18 years) to 70 years old inclusive will be recruited. Participants will be adults who have developed the early symptoms of COVID-19 within the first 5 days, or tested positive for SARS-CoV-2 within the first 7 days of symptom onset, or not presenting symptoms but tested positive within the last 48 hours (date/time of test must be within 48 hours of enrolment).
Eligible participants will be randomised 1:1:1:1 to receive one of the following combinations:
Favipiravir + Lopinavir/ritonavir (LPV/r) (both active); Favipiravir active + Lopinavir/ritonavir (LPV/r) placebo; Favipiravir placebo + Lopinavir/ritonavir (LPV/r) active; Favipiravir placebo + Lopinavir/ritonavir (LPV/r) placebo;
All participants will be enrolled and followed up for 28 days. A saliva sample for virological analysis and safety blood samples will be collected at baseline, as well as a diagnostic nose and throat swab, if the participant hasn't been tested for COVID-19 yet. Following randomisation, participants will take trial medication for 7 days and during this period will take a daily saliva sample and complete a symptoms diary including four daily temperature measurements.
Participants will have two follow-up visits at Day 7 and Day 14 where they will be assessed and undergo blood tests for toxicity and pharmacokinetic assessment (on Day 7 only) and provide stool samples. Participants will have a telephone follow up three (3) weeks after their last day of treatment (Day 7) and further information will be collected through a questionnaire.
- Conditions
- COVID-19
- Being tested
- Favipiravir, Lopinavir/ Ritonavir, Favipiravir Placebo, Lopinavir/ Ritonavir Placebo
- Medical subject headings
- COVID-19
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
FavipiravirDrug
Also called Avigan
Dosage and method of administration: Day 1: 1800 mg twice daily; Day 2 to Day 7: 400 mg four (4) times daily.
Lopinavir/ RitonavirDrug
Also called Kaletra
Dosage and method of administration: Day 1: 400mg/100 mg twice daily; Day 2 to Day 7: 200mg/50mg four (4) times daily
Favipiravir PlaceboOther
Dosage and method of administration: Day 1: 1800 mg twice daily; Day 2 to Day 7: 400 mg four (4) times daily.
Lopinavir/ Ritonavir PlaceboOther
Dosage and method of administration: Day 1: 1800 mg twice daily; Day 2 to Day 7: 400 mg four (4) times daily.
| Study group | Role | What they receive |
|---|---|---|
| Favipiravir + Lopinavir/ritonavir (LPV/r) | Experimental | Oral 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 Receives: Drug: Favipiravir; Drug: Lopinavir/ Ritonavir |
| Favipiravir + Lopinavir/ritonavir (LPV/r) placebo | Experimental | Oral 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. Receives: Drug: Favipiravir; Other: Lopinavir/ Ritonavir Placebo |
| Favipiravir placebo + Lopinavir/ritonavir (LPV/r) | Experimental | Oral 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. Receives: Drug: Lopinavir/ Ritonavir; Other: Favipiravir Placebo |
| Favipiravir placebo + Lopinavir/ritonavir (LPV/r) placebo | Placebo comparator | Oral 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. Receives: Other: Favipiravir Placebo; Other: Lopinavir/ Ritonavir Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Upper respiratory tract viral load at Day 5
Quantitative polymerase chain reaction (PCR) performed on saliva samples at Day 5 of therapy
Measured: Day 5 from randomisation
Secondary outcomes (20)
Percentage of participants with undetectable upper respiratory tract viral load after 5 days of therapy
Quantitative polymerase chain reaction (PCR) performed on saliva samples at Day 5 of therapy
Measured: 5 days from randomisation
Proportion of participants with undetectable stool viral load after 7 days of therapy.
Quantitative polymerase chain reaction (PCR) performed on stool samples at Day 7
Measured: 7 days from randomisation
Rate of decrease in upper respiratory tract viral load during 7 days of therapy
PCR performed on daily saliva samples collected between Day 1 and Day 7 post-randomisation
Measured: 7 days
Duration of fever following commencement of medication
Daily body temperature records between Day 1 and Day 7 post-randomisation
Measured: 7 days
Proportion of participants with hepatotoxicity after 7 days of therapy
Standard diagnostic laboratory assays for liver transaminases, alkaline phosphatase and bilirubin
Measured: 7 days from randomisation
Proportion of participants with other medication-related toxicity after 7 days of therapy and 14 days post-randomisation
Determination of medication-related adverse events by investigators at Day 7 and Day 14 post-randomisation
Measured: Day 7 and Day 14 from randomisation
Proportion of participants admitted to hospital with COVID-19 related illness
Participant self-report, review of hospital records and discharge summaries within 28 days of randomisation
Measured: 28 days
Proportion of participants admitted to ICU with COVID-19 related illness
Participant self-report, review of hospital records and discharge summaries within 28 days of randomisation
Measured: 28 days
Proportion of participants who have died with COVID-19 related illness
Participant self-report, review of hospital records and discharge summaries within 28 days of randomisation
Measured: 28 days
Pharmacokinetics of favipiravir as measured by Clearance (CL)
Assess pharmacokinetics of favipiravir as measured by Clearance (CL)
Measured: Day 7 from randomisation
Pharmacokinetics of favipiravir as measured by Volume of distribution (V)
Assess pharmacokinetics of favipiravir as measured by Volume of distribution (V)
Measured: Day 7 from randomisation
Pharmacokinetics of favipiravir as measured by Absorption rate constant (Ka)
Assess pharmacokinetics of favipiravir as measured by Absorption rate constant (Ka)
Measured: Day 7 from randomisation
Pharmacokinetics of favipiravir as measured by Maximum concentration (Cmax)
Assess pharmacokinetics of favipiravir as measured by Maximum concentration (Cmax)
Measured: Day 7 from randomisation
Pharmacokinetics of favipiravir as measured by Time to maximum concentration (Tmax)
Assess pharmacokinetics of favipiravir as measured by Time to maximum concentration (Tmax)
Measured: Day 7 from randomisation
Pharmacokinetics of favipiravir as measured by Elimination rate constant (Ke)
Assess pharmacokinetics of favipiravir as measured by Elimination rate constant (Ke)
Measured: Day 7 from randomisation
Pharmacokinetics of favipiravir as measured by Area Under the Curve extrapolated to infinity (AUC (0-inf)
Assess pharmacokinetics of favipiravir as measured by Area Under the Curve extrapolated to infinity (AUC (0-inf)
Measured: Day 7 from randomisation
Pharmacodynamics of favipiravir as measured by Rate of viral load decline (delta)
Assess pharmacodynamics of favipiravir as measured by Rate of viral load decline (delta)
Measured: Day 7 from randomisation
Pharmacodynamics of favipiravir as measured by Maximum increase in viral load under drug treatment (Emax)
Assess pharmacodynamics of favipiravir as measured by Maximum increase in viral load under drug treatment (Emax)
Measured: Day 7 from randomisation
Pharmacodynamics of favipiravir as measured by Concentration to achieve half the maximum possible effect (EC50)
Assess pharmacodynamics of favipiravir as measured by Concentration to achieve half the maximum possible effect (EC50)
Measured: Day 7 from randomisation
Proportion of participants with deleterious or resistance-conferring mutations in SARS-CoV-2 by Day 7 of treatment
Deep sequencing of virus and bioinformatic analysis
Measured: Day 7 from randomisation
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Aug 2020
- Study start24 Sep 2020
- Primary completion1 Dec 2021
- Study completion17 Jan 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for COVID-19Studies of the same condition, open and under way.
- More trials run by University College, LondonThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Factorial
- Model description
- Randomised, double-blind, 2x2 factorial placebo-controlled
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 240 participants (actual)
Sponsor and investigators
- Lead sponsor
- University College, London
- Sponsor type
- University, hospital or other
- Collaborators
- LifeArc
- Responsible party
- Sponsor
- Investigators
- David Lowe, Principal investigator, Institute of Immunity and Transplantation, University College London
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04499677
- Sponsor's protocol ID
- 132084
- Acronym
- FLARE
- Status last verified
- Dec 2021
- First submitted
- 16 Jun 2020
- Last updated
- 15 Dec 2022
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: No plan to share IPD has been made at this time.
Publications
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.
PubMed 36260627Brown 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.
PubMed 33685502
Study at a glance
From the registry record, last updated by the sponsor on 15 Dec 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Favipiravir, Lopinavir/Ritonavir or Combination Therapy: a Randomised, Double Blind, 2x2 Factorial Placebo-controlled Trial of Early Antiviral Therapy in COVID-19
- ClinicalTrials.gov ID
- NCT04499677
- Acronym / sponsor ID
- FLARE / 132084
- Conditions
- COVID-19
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 240 participants (actual)
- Lead sponsor
- University College, LondonUniversity, hospital or other
- Collaborators
- LifeArc
- Study start
- 24 Sep 2020 (actual)
- Primary completion
- 1 Dec 2021 (actual)
- Study completion
- 17 Jan 2022 (actual)
- First posted
- 5 Aug 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
FLARE is a phase IIA randomised, double-blind, 2x2 factorial placebo-controlled, interventional trial in which 240 participants, aged 18 years (≥ 18 years) to 70 years old inclusive will be recruited. Participants will be adults who have developed the early symptoms of COVID-19 within the first 5 days, or tested positive for SARS-CoV-2 within the first 7 days of symptom onset, or not presenting symptoms but tested positive within the last 48 hours (date/time of test must be within 48 hours of enrolment).
Eligible participants will be randomised 1:1:1:1 to receive one of the following combinations:
Favipiravir + Lopinavir/ritonavir (LPV/r) (both active); Favipiravir active + Lopinavir/ritonavir (LPV/r) placebo; Favipiravir placebo + Lopinavir/ritonavir (LPV/r) active; Favipiravir placebo + Lopinavir/ritonavir (LPV/r) placebo;
All participants will be enrolled and followed up for 28 days. A saliva sample for virological analysis and safety blood samples will be collected at baseline, as well as a diagnostic nose and throat swab, if the participant hasn't been tested for COVID-19 yet. Following randomisation, participants will take trial medication for 7 days and during this period will take a daily saliva sample and complete a symptoms diary including four daily temperature measurements.
Participants will have two follow-up visits at Day 7 and Day 14 where they will be assessed and undergo blood tests for toxicity and pharmacokinetic assessment (on Day 7 only) and provide stool samples. Participants will have a telephone follow up three (3) weeks after their last day of treatment (Day 7) and further information will be collected through a questionnaire.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Factorial
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 4
- Model description
- Randomised, double-blind, 2x2 factorial placebo-controlled
| Arm | Type | Receives |
|---|---|---|
| Favipiravir + Lopinavir/ritonavir (LPV/r) | Experimental | Drug: Favipiravir, Drug: Lopinavir/ RitonavirOral 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 | Experimental | Drug: Favipiravir, Other: Lopinavir/ Ritonavir PlaceboOral 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) | Experimental | Drug: Lopinavir/ Ritonavir, Other: Favipiravir PlaceboOral 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 comparator | Other: Favipiravir Placebo, Other: Lopinavir/ Ritonavir PlaceboOral 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. |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- Any adult with the following:
- 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
Key exclusion criteria (11 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| FavipiravirAlso: AviganDosage and method of administration: Day 1: 1800 mg twice daily; Day 2 to Day 7: 400 mg four (4) times daily. | Drug | Favipiravir + Lopinavir/ritonavir (LPV/r), Favipiravir + Lopinavir/ritonavir (LPV/r) placebo |
| Lopinavir/ RitonavirAlso: KaletraDosage and method of administration: Day 1: 400mg/100 mg twice daily; Day 2 to Day 7: 200mg/50mg four (4) times daily | Drug | Favipiravir + Lopinavir/ritonavir (LPV/r), Favipiravir placebo + Lopinavir/ritonavir (LPV/r) |
| Favipiravir PlaceboDosage and method of administration: Day 1: 1800 mg twice daily; Day 2 to Day 7: 400 mg four (4) times daily. | Other | Favipiravir placebo + Lopinavir/ritonavir (LPV/r), Favipiravir placebo + Lopinavir/ritonavir (LPV/r) placebo |
| Lopinavir/ Ritonavir PlaceboDosage and method of administration: Day 1: 1800 mg twice daily; Day 2 to Day 7: 400 mg four (4) times daily. | Other | Favipiravir + Lopinavir/ritonavir (LPV/r) placebo, Favipiravir placebo + Lopinavir/ritonavir (LPV/r) placebo |
Primary outcome
Upper respiratory tract viral load at Day 5
Time frame: Day 5 from randomisation
Quantitative polymerase chain reaction (PCR) performed on saliva samples at Day 5 of therapy
20 secondary outcomes
Percentage of participants with undetectable upper respiratory tract viral load after 5 days of therapy
Time frame: 5 days from randomisation
Proportion of participants with undetectable stool viral load after 7 days of therapy.
Time frame: 7 days from randomisation
Rate of decrease in upper respiratory tract viral load during 7 days of therapy
Time frame: 7 days
Duration of fever following commencement of medication
Time frame: 7 days
Proportion of participants with hepatotoxicity after 7 days of therapy
Time frame: 7 days from randomisation
Proportion of participants with other medication-related toxicity after 7 days of therapy and 14 days post-randomisation
Time frame: Day 7 and Day 14 from randomisation
Proportion of participants admitted to hospital with COVID-19 related illness
Time frame: 28 days
Proportion of participants admitted to ICU with COVID-19 related illness
Time frame: 28 days
Proportion of participants who have died with COVID-19 related illness
Time frame: 28 days
Pharmacokinetics of favipiravir as measured by Clearance (CL)
Time frame: Day 7 from randomisation
Pharmacokinetics of favipiravir as measured by Volume of distribution (V)
Time frame: Day 7 from randomisation
Pharmacokinetics of favipiravir as measured by Absorption rate constant (Ka)
Time frame: Day 7 from randomisation
Pharmacokinetics of favipiravir as measured by Maximum concentration (Cmax)
Time frame: Day 7 from randomisation
Pharmacokinetics of favipiravir as measured by Time to maximum concentration (Tmax)
Time frame: Day 7 from randomisation
Pharmacokinetics of favipiravir as measured by Elimination rate constant (Ke)
Time frame: Day 7 from randomisation
Pharmacokinetics of favipiravir as measured by Area Under the Curve extrapolated to infinity (AUC (0-inf)
Time frame: Day 7 from randomisation
Pharmacodynamics of favipiravir as measured by Rate of viral load decline (delta)
Time frame: Day 7 from randomisation
Pharmacodynamics of favipiravir as measured by Maximum increase in viral load under drug treatment (Emax)
Time frame: Day 7 from randomisation
Pharmacodynamics of favipiravir as measured by Concentration to achieve half the maximum possible effect (EC50)
Time frame: Day 7 from randomisation
Proportion of participants with deleterious or resistance-conferring mutations in SARS-CoV-2 by Day 7 of treatment
Time frame: Day 7 from randomisation
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Dec 2022.
- Derived from this study: PubMed 36260627Lowe 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.
- Derived from this study: PubMed 33685502Brown 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.
- trial resultsLink provided by the sponsor.
- Initial trial ProtocolLink provided by the sponsor.
- Individual participant dataSharing planned: No. No plan to share IPD has been made at this time.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
David Lowe principal investigator
Institute of Immunity and Transplantation, University College London
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Favipiravir and Lopinavir/ Ritonavir in people with COVID-19, run by University College, London at 2 sites in United Kingdom.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 15 Dec 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Upper respiratory tract viral load at Day 5 (time frame: Day 5 from randomisation). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04499677, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Dec 2022.