Covid-19 Living Data

Trial NCT04600895
Publication PRESECO - Golan Y, Clin Infect Dis (2022) (published paper)
Dates: 2020-11-30 to 2021-10-20
Funding: Private (The conduct of this clinical trial and the preparation of this manuscript were supported by Appili Therapeutics, Inc., Halifax, NS, Canada.)
Conflict of interest: Yes

Methods
	RCT Blinding: double blinding
	Location : Multicenter / USA (27 sites), Brazil (7 sites) and Mexico (6 sites) Follow-up duration (days): 28
Inclusion criteria	Age 18 years or older Mild-to-moderate COVID-19 First positive reverse transcription polymerase chain reaction (RT-PCR) or Rapid Antigen assay within 3 days of enrollment First symptoms within 5 days of enrollment Having at least 2 moderate or severe COVID-19 symptoms signing an informed consent COVID-19-related symptoms included runny nose, sore throat, shortness of breath, cough, tiredness, body aches, headache, chills, feeling feverish, nausea, diarrhea, and vomiting. Early in the trial, taste or smell changes were included in the entry criteria, however, later, based on an evolving understanding of COVID-19 symptom time course, taste and smell were excluded. Subjects enrolled based solely on taste and smell changes were not analyzed Males must be sterile, OR agree not to donate semen AND agree to strictly adhere to contraceptive measures (e.g., condom use) during the study and for 7 days following the last dose of study treatment Females must be unable to bear children OR ensure that their male partner is incapable of fathering a child, OR, if of childbearing potential will strictly adhere to contraceptive measures during the study and for seven days following the last dose of study treatment Females must agree to stop breast-feeding prior to first dose of study drug and through 7 days after completing therapy Females must have a negative pregnancy test at screening
Exclusion criteria	O2 saturation <94% Shortness of breath at rest Heart rate ≥125 beats per minute COVID-19 symptoms first presented >5 days prior to randomization Requirement for hospitalization at the time of enrollment Participation in another trial or use of any experimental treatment for COVID-19 Treatment with high steroid dose, i.e., >30 mg/day prednisolone equivalent (excluding stable chronic treatment) or remdesivir or anyone receiving SARS-CoV-2 monoclonal antibodies within 3 months prior to enrollment Known sepsis or organ dysfunction/failure Known infection with a respiratory virus other than SARS-CoV-2 (e.g., Influenza) or any known bacterial infection (affecting the respiratory system or any other system) Inability to adhere to study requirements For premenopausal women: unwilling or unable to use effective birth control measures Known allergy to favipiravir Known end-stage kidney disease or requiring hemodialysis or continuous ambulatory peritoneal dialysis (CAPD) Known liver impairment greater than Child-Pugh A Psychiatric illness that is not well controlled (defined as stable on a regimen for more than one year) Known elevated uric acid levels in the past year or taking uric acid lowering medications (allopurinol, febuxostat) History of hereditary xanthinuria or history of xanthine urolithiasis History of gout or actively being treated for gout
Interventions
	Treatment Favipiravir Initial dose: 1800 mg orally twice daily on Day 1 -Maintenance dose: 800 mg orally twice daily on Days 2–10
	Control Placebo
Participants
	Randomized NR Analyzed 1211 participants Favipiravir=610 Placebo=601
	Characteristics of participants N= 1211 Mean age : NR 543 males Severity : Mild: n= 1211/ Asymptomatic: n=0 Number of vaccinated participants: NR
Primary outcome
	In the register Time to sustained clinical recovery [Time Frame: From Day 0 to Day 28]: The endpoint will be considered to have been met at the earliest time point at which the subject has reached Sustained Alleviation of Symptoms (Symptoms related to smell or taste are not included in the primary endpoint) reported by the patient have reached a severity of "0 - none" or "1 - mild" in assessments for 4-point scale assessments and not known to have redeveloped any COVID-19 associated signs and symptoms (not including reduced sense of taste or smell) in a severity beyond mild for 4 consecutive days when assessed from the start of study treatment to day 28. To meet the primary endpoint, subjects must survive with no hospitalization to day 28.
	In the report Time to Sustained Clinical Recovery, calculated as the number of days from start of study medication to sustained symptom alleviation, defined by: Oxygen saturation ≥94% at rest, and Oral temperature <38.0°C, and all COVID-19-associated symptoms reaching a score of mild or none for 4 consecutive days.
Documents available	Protocol NR Statistical plan NR Data-sharing willing stated in the publication: Not reported
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 and its supplement, the study registry was used in data extraction and risk of bias assessment. The study achieved the target sample size specified in the trial registry. There is no change from the trial registration in the intervention and control treatments. The registry primary outcome reflects the reported primary outcome.