Japanease

Mar. 02, 2020

Aug. 31, 2020

jRCTs041190120

Multicenter, open-label, randomized trial of favipiravir in asymptomatic and minimally symptomatic patients infected with SARS-CoV2 to evaluate viral load reduction

Favipiravir for SARS-CoV-infected patients

June. 15, 2020

89

89 patients (median age, 50 years; 54 [60.7%] male) were enrolled. One patient in the delayed treatment group withdrew immediately after randomization and was excluded from analysis. Sixty-nine had a positive PCR on Day1.

Between March 2, 2020 and May 18, 2020, 89 patients signed the informed consent form. All 89 participants were enrolled and randomly assigned to a treatment group (44 to the early treatment and 45 to the delayed treatment).

There were 101 adverse events that may have been associated with the drug. There was one reportable serious adverse event (prolongation of hospitalization). Hyperuricemia was the most common adverse event, which occurred in 69/82 (84.1%). Hyperuricemia was transient and resolved in most patients.

Primary endpoint; Clearance of SARS-CoV2 by Day6 was achieved in 66.7% of the early treatment group and 56.1% of the delayed treatment group (adjusted hazard ratio, 1.42; 95% CI, 0.76-2.62). Secondary endpoints; (1) Clearance of SARS-CoV2 by Day10 was achieved in 86.1% of the early treatment group and 83.1% of the delayed treatment group (adjusted hazard ratio, 1.27; 95% CI, 0.74-2.17). (2) 50% reduction in SARS-CoV2 copy number was achieved in 94.4% of the early treatment group and 78.8% of the delayed treatment group (adjusted odds ratio, 4.75; 95% CI, 0.88-25.76). (3) Changes in SARS-CoV2 copy number on a logarithmic scale did not reach statistical significance over time.

89 participants were enrolled into this study. Favipiravir did not significantly improve viral clearance by the sixth. However, there was a trend towards earlier viral clearance with the agent.

Aug. 31, 2020

Yes

After approval from Japan Agency for Medical Research and Development (AMED), this trial data can be shared with qualifying researchers who submit a proposal with a valuable research question. A contract should be signed.

https://jrct.niph.go.jp/latest-detail/jRCTs041190120

Doi Yohei

Fujita Health University Hospital

1-98 Dengakugakubo, Kutsukake, Toyoake, Aichi 470-1192, Japan

+81-562-93-2433

yoheidoi@fujita-hu.ac.jp

Kondo Masashi

Fujita Health University Hospital

1-98 Dengakugakubo, Kutsukake, Toyoake, Aichi 470-1192, Japan

+81-562-93-9407

mkond@fujita-hu.ac.jp

Mar. 02, 2020

86

Interventional

randomized controlled trial

open(masking not used)

no treatment control

parallel assignment

treatment purpose

none

(1) Age 16 or greater at the time of consent
(2) Sex; male or female
(3) Outpatient or inpatient: inpatient
(4) Meets all of 1), 2), 3) below
1)Has at least one RT-PCR test positive for SARS-CoV2 from pharyngeal or nasopharyngeal swab (date of collection must be within 14 days before enrollment)
2) Has a performance status of 0 or 1
3) Is able to remain inpatient for 6 days
(5) Has a negative pregnancy test if the subject is female and pre-menopausal
(6) Has provided written consent for participation; written consents from both the subject and a legal guardian

(1) Performance status of 2 or greater
(2) Advanced liver function abnormalities classified as grade C by the Child-Pugh criteria
(3) End-stage renal disease requiring dialysis
(4) Altered mental status
(5) Pregnant or planning pregnancy
(6) If female, not agreeable to using oral contraceptive, intrauterine contraceptive device, mechanical contraceptive methods such as pessaries and condoms, or combinations thereof, during favipiravir administration and 90 days thereafter
(7) If male, has a female partner who is not agreeable to the contraceptive methods described in (7)
(8) If male, not agreeable to using condoms during favipiravir administration and 90 days thereafter
(9) History of hereditary xanthine oxidase deficiency
(10) History of hypouricemia (less than 1 mg/dL) or xanthine urolithiasis
(11) History of uncontrolled gout or hyperuricemia
(12) History of immunocompromising conditions such as HIV positivity
(13) Has received systemic agents with suggested activity against SARS-CoV2 within 28 days before enrollment
(14) Deemed ineligible as determined by the principal investigator or a co-investigator

16age old over
No limit

Both

COVID-19 infection

Immediate favipiravir arm: Favipiravir administered orally between Day 1 and Day 10, 1800 mg twice a day on Day 1 followed by 800 mg twice a day from Day 2
Delayed favipiravir arm: Favipiravir administered orally between Day 6 and Day 15, 1800 mg twice a day on Day 6 followed by 800 mg twice a day from Day 7

006

COVID-19 infection

Proportion of subjects with clearance of SARS-CoV2 in nasopharyngeal swab by Day 6

Proportion of subjects with clearance of SARS-CoV2 in nasopharyngeal swab by Day 11
Proportion of subjects with 50% reduction in SARS-CoV2 copy number in nasopharyngeal swab on a logarithmic scale
Change of SARS-CoV2 copy number on a logarithmic scale

Complete

Japan Agency for Medical Research and Development
Not applicable
Fujita Health University Certified Clinical Research Review Board
1-98 Dengakugakubo, Kutsukake-cho, Toyoake, Japan, Aichi

+81-562-93-2865

f-irb@fujita-hu.ac.jp
Approval

Feb. 28, 2020