Clinical effectiveness, safety, and viral mutagenicity of oral favipiravir for COVID-19: results from a community-based, open-label, randomized Phase III trial
Bibliographic record
Abstract
ABSTRACT Early community treatment of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection may reduce severe coronavirus disease (COVID-19) incidence. We evaluated clinical effectiveness, safety, and SARS-CoV-2 mutagenicity of favipiravir, an oral viral RNA polymerase inhibitor. We performed an open-label, community-based, randomized Phase III trial, recruiting non-hospitalized adults with mild COVID-19 (WHO ordinal severity score [OSS] ≤ 3). Positive cases were invited to web-based self-screening within 24 h using public health data. Exclusion criteria included symptoms for >7 days, pregnancy/breastfeeding, severe renal/liver disease, gout, and licensed antiviral eligibility. Participants were randomized 1:1 to 10 days favipiravir (Day 1: 3,600 mg; days 2-10: 1,600 mg) or no additional treatment. The primary endpoint was worst recorded OSS up to and including Day 15 (intention-to-treat). The target recruitment was 302. Secondary endpoints included adverse event (AE) rate to Day 60, time-to-viral clearance (TTVC), time-to-symptom resolution (TTSR), and SARS-CoV-2 sequencing variant rate (≥5% frequency) at Day 15 (registration ISRCTN: 31062548; EudraCT: 2020-001904-41). A total of 68,788 adults were invited, and 302 (0.4%) were subsequently randomized between December 2020 and July 2022 (favipiravir [ n = 152]: standard care [ n = 150]). Mean (SD) age was 47.2 (13.2), and 230/302 (76%) were vaccinated. Severe outcomes were infrequent, with no intensive care unit admissions/deaths. There was no difference in the primary endpoint: odds ratio 1.18 (95% confidence interval [CI] 0.63–2.20), TTSR (HR 1.03 [95% CI 0.81–1.31]), or TTVC (HR 1.13 [95% CI 0.65–1.97]). Favipiravir was well tolerated with few AEs but was associated with increased variant frequency, including C-to-U mutations. Community administration of favipiravir for mild COVID-19 was not associated with clinical benefits or safety concerns but was associated with SARS-CoV-2 mutagenicity. CLINICAL TRIALS This study is registered with ISRCTN as 31062548 and with EU-CTR as 2020-001904-41 .
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.005 | 0.004 |
| Meta-epidemiology (narrow) | 0.002 | 0.001 |
| Meta-epidemiology (broad) | 0.003 | 0.002 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.001 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.002 | 0.003 |
| Insufficient payload (model declined to judge) | 0.006 | 0.001 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".