Trial NCT04499677
Publication FLARE - Lowe DM, PLoS Med (2022) (published paper)
Dates: 2020-10-06 to 2021-11-04
Funding: Mixed (LifeArc, UK; Fujifilm Toyama Chemical Co. provided favipiravir and favipiravir placebo free of charge.)
Conflict of interest: Yes

Methods
RCT
Blinding: double blinding
Location : Multicenter / UK
Follow-up duration (days): 28
Inclusion criteria
  • Aged between 18 and 70 years
  • Recently (within the last 5 days) developed symptoms of COVID-19
  • Tested positive for SARS-CoV-2 by PCR
  • Were within 7 days of symptom onset, or who were asymptomatic but had tested positive by PCR within the previous 48 hours
Exclusion criteria
  • Known hypersensitivity to either drug or their ingredients/excipients
  • Chronic liver or kidney disease
  • Taking concomitant medicines known to interact with the trial treatments
  • Being treated as a hospital inpatient for any condition
  • Pregnant or breastfeeding
  • Participating in another interventional clinical trial (treatment or vaccination)
  • Female participants of childbearing potential were required to provide a negative pregnancy test before commencement of trial medication and on Day 14, and to use highly effective contraceptive measures during the trial
  • Male participants with a female partner of childbearing potential were also required to use highly effective contraception
Interventions
Treatment
LPV/r+FAV
Initial dose: 1800 mg FAV + 400/100 mg LPV/r orally twice a day on Day 1 -Maintenance dose: 400 mg FAV + 200/50 mg LPV/r orally 4 times a day on Days 2-7.

Lopinavir-Ritonavir
Initial dose: 400/100 mg LPV/r orally twice a day on Day 1 -Maintenance dose: 200/50 mg LPV/r orally 4 times a day on Days 2-7.

Favipiravir
Initial dose: 1800 mg FAV orally twice a day on Day 1 -Maintenance dose: 400 mg orally 4 times a day on Days 2-7.
Control
Placebo

Participants
Randomized
participants :
Placebo=60
LPV/r+FAV=61
Lopinavir-Ritonavir =60
Favipiravir=59
Characteristics of participants
N= 240
Mean age : NR
123 males
Severity : Mild: n= 239/ Asymptomatic: n=1
Number of vaccinated participants: 27
Primary outcome
In the register
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
In the report
Viral load measured by quantitative polymerase chain reaction (PCR) performed on saliva samples at Day 5
Documents
available

Protocol

Yes. In English

Statistical plan

Yes

Data-sharing willing stated in the publication:

Yes
Risk of bias
Overall
The overall risk of bias reported in the table corresponds to the highest risk of bias for the outcomes assessed for the systematic review
Some concerns
General comment In addition to the published article, the pre-print article, protocol, statistical analysis plan and prospective study registry were used in data extraction and risk of bias assessment. There is no change from the trial registration in the intervention and control treatments. The registry primary outcome reflects the reported primary outcome. The study (n=240) achieved the target sample size (n=240) specified in the trial registry.
This study was updated on August 8th, 2022 with data obtained from contact with authors.
This study was updated on January 19th, 2023 with data extracted from the published report.