Dataset Information

A Prospective, Randomized, Open-Label Trial of Early versus Late Favipiravir Therapy in Hospitalized Patients with COVID-19.

ABSTRACT: Favipiravir is an oral broad-spectrum inhibitor of viral RNA-dependent RNA polymerase that is approved for treatment of influenza in Japan. We conducted a prospective, randomized, open-label, multicenter trial of favipiravir for the treatment of COVID-19 at 25 hospitals across Japan. Eligible patients were adolescents and adults admitted with COVID-19 who were asymptomatic or mildly ill and had an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. Patients were randomly assigned at a 1:1 ratio to early or late favipiravir therapy (in the latter case, the same regimen starting on day 6 instead of day 1). The primary endpoint was viral clearance by day 6. The secondary endpoint was change in viral load by day 6. Exploratory endpoints included time to defervescence and resolution of symptoms. Eighty-nine patients were enrolled, of whom 69 were virologically evaluable. Viral clearance occurred within 6?days in 66.7% and 56.1% of the early and late treatment groups (adjusted hazard ratio [aHR], 1.42; 95% confidence interval [95% CI], 0.76 to 2.62). Of 30 patients who had a fever (?37.5°C) on day 1, times to defervescence were 2.1?days and 3.2?days in the early and late treatment groups (aHR, 1.88; 95% CI, 0.81 to 4.35). During therapy, 84.1% developed transient hyperuricemia. Favipiravir did not significantly improve viral clearance as measured by reverse transcription-PCR (RT-PCR) by day 6 but was associated with numerical reduction in time to defervescence. Neither disease progression nor death occurred in any of the patients in either treatment group during the 28-day participation. (This study has been registered with the Japan Registry of Clinical Trials under number jRCTs041190120.).

SUBMITTER: Doi Y

PROVIDER: S-EPMC7674035 | biostudies-literature | 2020 Nov

REPOSITORIES: biostudies-literature

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A Prospective, Randomized, Open-Label Trial of Early versus Late Favipiravir Therapy in Hospitalized Patients with COVID-19.

Doi Yohei Y Hibino Masaya M Hase Ryota R Yamamoto Michiko M Kasamatsu Yu Y Hirose Masahiro M Mutoh Yoshikazu Y Homma Yoshito Y Terada Masaki M Ogawa Taku T Kashizaki Fumihiro F Yokoyama Toshihiko T Koba Hayato H Kasahara Hideki H Yokota Kazuhisa K Kato Hideaki H Yoshida Junichi J Kita Toshiyuki T Kato Yasuyuki Y Kamio Tadashi T Kodama Nobuhiro N Uchida Yujiro Y Ikeda Nobuhiro N Shinoda Masahiro M Nakagawa Atsushi A Nakatsumi Hiroki H Horiguchi Tomoya T Iwata Mitsunaga M Matsuyama Akifumi A Banno Sumi S Koseki Takenao T Teramachi Mayumi M Miyata Masami M Tajima Shigeru S Maeki Takahiro T Nakayama Eri E Taniguchi Satoshi S Lim Chang Kweng CK Saijo Masayuki M Imai Takumi T Yoshida Hisako H Kabata Daijiro D Shintani Ayumi A Yuzawa Yukio Y Kondo Masashi M

Antimicrobial agents and chemotherapy 20201117 12

Favipiravir is an oral broad-spectrum inhibitor of viral RNA-dependent RNA polymerase that is approved for treatment of influenza in Japan. We conducted a prospective, randomized, open-label, multicenter trial of favipiravir for the treatment of COVID-19 at 25 hospitals across Japan. Eligible patients were adolescents and adults admitted with COVID-19 who were asymptomatic or mildly ill and had an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. Patients were randomly assi ...[more]

PMID: 32958718

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Project description:Background: In addition to supportive therapy, antiviral therapy is an effective treatment for coronavirus disease 2019 (COVID-19). Objective: To compare the efficacy and safety of favipiravir and umifenovir (Arbidol) to treat COVID-19 patients. Methods: We conducted a prospective, randomized, controlled, open-label multicenter trial involving adult patients with COVID-19. Enrolled patients with initial symptoms within 12 days were randomly assigned in a 1:1 ratio to receive conventional therapy plus Arbidol (200 mg*3/day) or favipiravir (1600 mg*2/first day followed by 600 mg*2/day) for 7 days. The primary outcome was the clinical recovery rate at day 7 of drug administration (relief for pyrexia and cough, respiratory frequency ≤24 times/min; oxygen saturation ≥98%). Latency to relief for pyrexia and cough and the rate of auxiliary oxygen therapy (AOT) or noninvasive mechanical ventilation (NMV)/mechanical ventilation (MV) were the secondary outcomes. Safety data were collected for 17 days. Results: A total of 240 enrolled COVID-19 patients underwent randomization; 120 patients were assigned to receive favipiravir (116 assessed), and 120 patients were assigned to receive Arbidol (120 assessed). The clinical recovery rate at day 7 of drug administration did not significantly differ between the favipiravir group (71/116) and Arbidol group (62/120) (p = 0.1396, difference in recovery rate: 0.0954; 95% CI: -0.0305∼0.2213). Favipiravir contributed to relief for both pyrexia (difference: 1.70 days, p < 0.0001) and cough (difference: 1.75 days, p < 0.0001). No difference was observed in the AOT or NMV/MV rate (both p > 0.05). The most frequently observed favipiravir-associated adverse event was increased serum uric acid (16/116, OR: 5.52, p = 0.0014). Conclusion: Among patients with COVID-19, favipiravir, compared to Arbidol, did not significantly improve the clinical recovery rate at day 7. Favipiravir significantly improved the latency to relieve pyrexia and cough. Adverse effects caused by favipiravir are mild and manageable.

Project description:BackgroundThe role of ivermectin in the treatment of moderate coronavirus disease 2019 (COVID-19) is controversial. We performed an open label randomized controlled trial to evaluate the role of ivermectin plus favipiravir-based standard of care versus favipiravir-based standard of care for the treatment of moderate COVID-19 infection.Materials and methodsAn open-label randomized control trial was performed at Thammasat Field Hospital and Thammasat University Hospital from October 1st, 2021 to May 31st, 2022. Patients with moderate COVID-19 infections were randomized to the intervention (ivermectin plus favipiravir-based standard of care) or control group (favipiravir-based standard of care alone). Patients were followed up to 21 days. The primary outcome was the improvement in World Health Organization (WHO) category ordinal scale by 2 points. Secondary outcomes included duration of illness, development of severe COVID-19, and adverse reactions.ResultsThere were 157 patients in the intervention and 160 patients in the control group. Characteristics, underlying diseases, and risk factors for severe COVID-19 were comparable in both groups. Improvement in the WHO-category ordinal scale by 2 points was achieved in 98.7% of the intervention group and in 99.4% of the control group (relative risk [RR]: 0.487; 95% confidence interval [CI]: 0.044-5.430). The median illness duration was 5.0 days (range, 3 - 28 days) in intervention group versus 5.2 days (range, 3 - 28 days) in control group (P = 0.630). Severe COVID-19 that required intensive care occurred in 2 patients (1.3%) in the intervention group and 1 patient (0.6%) in the control group (RR: 2.052; 95% CI: 0.184 - 22.857). No significant difference in serious drug adverse events was seen.ConclusionIn this study ivermectin plus standard of care was not associated with improvement in the WHO-category ordinal scale, reduced illness duration, or development of severe COVID-19 in moderately ill COVID-19 patients.Trial registrationClinicaltrials.gov Identifier: TCTR20220427005.

Project description:AimsThere is rising healthcare utilization related to the increasing incidence and prevalence of atrial fibrillation (AF) worldwide. Simplifying therapy and reducing hospital episodes would be a valuable development. The efficacy of a streamlined AF ablation approach was compared to drug therapy and a conventional catheter ablation technique for symptom control in paroxysmal AF.Methods and resultsWe recruited 321 patients with symptomatic paroxysmal AF to a prospective randomized, multi-centre, open label trial at 13 UK hospitals. Patients were randomized 1:1:1 to cryo-balloon ablation without electrical mapping with patients discharged same day [Ablation Versus Anti-arrhythmic Therapy for Reducing All Hospital Episodes from Recurrent (AVATAR) protocol]; optimization of drug therapy; or cryo-balloon ablation with confirmation of pulmonary vein isolation and overnight hospitalization. The primary endpoint was time to any hospital episode related to treatment for atrial arrhythmia. Secondary endpoints included complications of treatment and quality-of-life measures. The hazard ratio (HR) for a primary endpoint event occurring when comparing AVATAR protocol arm to drug therapy was 0.156 (95% CI, 0.097-0.250; P < 0.0001 by Cox regression). Twenty-three patients (21%) recorded an endpoint event in the AVATAR arm compared to 76 patients (74%) within the drug therapy arm. Comparing AVATAR and conventional ablation arms resulted in a non-significant HR of 1.173 (95% CI, 0.639-2.154; P = 0.61 by Cox regression) with 23 patients (21%) and 19 patients (18%), respectively, recording primary endpoint events (P = 0.61 by log-rank test).ConclusionThe AVATAR protocol was superior to drug therapy for avoiding hospital episodes related to AF treatment, but conventional cryoablation was not superior to the AVATAR protocol. This could have wide-ranging implications on how demand for AF symptom control is met.Trial registrationClinical Trials Registration: NCT02459574.

Project description:IntroductionAntiviral drugs have shown limited effectiveness in treating patients with coronavirus disease 2019 (COVID-19). We aimed to assess the effects of a favipiravir and hydroxychloroquine combination on treating moderate-to-severe COVID-19 patients.MethodsAn investigator-initiated, multicenter, open-label, randomized trial at nine hospitals. Eligible patients were adults with moderate-to-severe COVID-19 defined as oxygen saturation (SaO2) of ≤ 94% while breathing ambient air or significant clinical symptoms with chest x-ray changes requiring hospital admission. Randomization was in a 1:1 ratio to receive standard care (control group) or standard care plus favipiravir and hydroxychloroquine. The primary outcome was time to clinical improvement of two points (from the status at randomization) on a seven-category ordinal scale or live discharge from the hospital within 14 days. Analyses were done in an intention-to-treat population.ResultsFrom May 2020 to Jan 2021, 254 patients were enrolled; 129 were assigned to standard of care and 125 to the treatment. The mean age was 52 (± 13) years, and 103 (41%) were women. At randomization, six patients were on invasive mechanical ventilation, 229 (90.15%) were requiring supplemental oxygen only (with or without non-invasive ventilation), and 19 (7.48%) were receiving neither. The time to clinical improvement was not significantly different between the groups: median of 9 days in the treatment group and 7 days in the control group (HR: 0.845; 95% CI 0.617-1.157; p-value = 0.29). The 28-day mortality was not significantly different between the groups (7.63% treatment) vs. (10.32% control); p-value = 0.45. The most prevalent adverse events were headache, elevation in ALT, and the prolonged QTc interval in the treatment group.ConclusionThe combination of favipiravir and hydroxychloroquine did not result in a statistically significant clinical benefit in patients with moderate-to-severe COVID-19.Clinical trial registrationClinicalTrials.gov (NCT04392973).

Project description:BackgroundCOVID-19 has overwhelmed health services globally. Oral antiviral therapies are licensed worldwide, but indications and efficacy rates vary. We aimed to evaluate the safety and efficacy of oral favipiravir in patients hospitalised with COVID-19.MethodsWe conducted a multicentre, open-label, randomised controlled trial of oral favipiravir in adult patients who were newly admitted to hospital with proven or suspected COVID-19 across five sites in the UK (n=2), Brazil (n=2) and Mexico (n=1). Using a permuted block design, eligible and consenting participants were randomly assigned (1:1) to receive oral favipiravir (1800 mg twice daily for 1 day; 800 mg twice daily for 9 days) plus standard care, or standard care alone. All caregivers and patients were aware of allocation and those analysing data were aware of the treatment groups. The prespecified primary outcome was the time from randomisation to recovery, censored at 28 days, which was assessed using an intention-to-treat approach. Post-hoc analyses were used to assess the efficacy of favipiravir in patients aged younger than 60 years, and in patients aged 60 years and older. The trial was registered with clinicaltrials.gov, NCT04373733.FindingsBetween May 5, 2020 and May 26, 2021, we assessed 503 patients for eligibility, of whom 499 were randomly assigned to favipiravir and standard care (n=251) or standard care alone (n=248). There was no significant difference between those who received favipiravir and standard care, relative to those who received standard care alone in time to recovery in the overall study population (hazard ratio [HR] 1·06 [95% CI 0·89-1·27]; n=499; p=0·52). Post-hoc analyses showed a faster rate of recovery in patients younger than 60 years who received favipiravir and standard care versus those who had standard care alone (HR 1·35 [1·06-1·72]; n=247; p=0·01). 36 serious adverse events were observed in 27 (11%) of 251 patients administered favipiravir and standard care, and 33 events were observed in 27 (11%) of 248 patients receiving standard care alone, with infectious, respiratory, and cardiovascular events being the most numerous. There was no significant between-group difference in serious adverse events per patient (p=0·87).InterpretationFavipiravir does not improve clinical outcomes in all patients admitted to hospital with COVID-19, however, patients younger than 60 years might have a beneficial clinical response. The indiscriminate use of favipiravir globally should be cautioned, and further high-quality studies of antiviral agents, and their potential treatment combinations, are warranted in COVID-19.FundingLifeArc and CW+.

Dataset Information

A Prospective, Randomized, Open-Label Trial of Early versus Late Favipiravir Therapy in Hospitalized Patients with COVID-19.

Publications

A Prospective, Randomized, Open-Label Trial of Early versus Late Favipiravir Therapy in Hospitalized Patients with COVID-19.

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