Dataset Information

Efficacy and safety of favipiravir, an oral RNA-dependent RNA polymerase inhibitor, in mild-to-moderate COVID-19: A randomized, comparative, open-label, multicenter, phase 3 clinical trial.

ABSTRACT:

Objective

To assess the efficacy and safety of favipiravir in adults with mild-to-moderate coronavirus disease 2019 (COVID-19).

Methods

In this randomized, open-label, parallel-arm, multicenter, phase 3 trial, adults (18-75 years) with RT-PCR confirmed COVID-19 and mild-to-moderate symptoms (including asymptomatic) were randomized 1:1 to oral favipiravir (day 1: 1800 mg BID and days 2-14: 800 mg BID) plus standard supportive care versus supportive care alone. The primary endpoint was time to the cessation of viral shedding; time to clinical cure was also measured.

Results

From May 14 to July 3, 2020, 150 patients were randomized to favipiravir (n = 75) or control (n = 75). Median time to the cessation of viral shedding was 5 days (95% CI: 4 days, 7 days) versus 7 days (95% CI: 5 days, 8 days), P = 0.129, and median time to clinical cure was 3 days (95% CI: 3 days, 4 days) versus 5 days (95% CI: 4 days, 6 days), P = 0.030, for favipiravir and control, respectively. Adverse events were observed in 36% of favipiravir and 8% of control patients. One control patient died due to worsening disease.

Conclusion

The lack of statistical significance on the primary endpoint was confounded by limitations of the RT-PCR assay. Significant improvement in time to clinical cure suggests favipiravir may be beneficial in mild-to-moderate COVID-19.

SUBMITTER: Udwadia ZF

PROVIDER: S-EPMC7668212 | biostudies-literature | 2021 Feb

REPOSITORIES: biostudies-literature

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Publications

Efficacy and safety of favipiravir, an oral RNA-dependent RNA polymerase inhibitor, in mild-to-moderate COVID-19: A randomized, comparative, open-label, multicenter, phase 3 clinical trial.

Udwadia Zarir F ZF Singh Pawan P Barkate Hanmant H Patil Saiprasad S Rangwala Shabbir S Pendse Amol A Kadam Jatin J Wu Wen W Caracta Cynthia F CF Tandon Monika M

International journal of infectious diseases : IJID : official publication of the International Society for Infectious Diseases 20201116

<h4>Objective</h4>To assess the efficacy and safety of favipiravir in adults with mild-to-moderate coronavirus disease 2019 (COVID-19).<h4>Methods</h4>In this randomized, open-label, parallel-arm, multicenter, phase 3 trial, adults (18-75 years) with RT-PCR confirmed COVID-19 and mild-to-moderate symptoms (including asymptomatic) were randomized 1:1 to oral favipiravir (day 1: 1800 mg BID and days 2-14: 800 mg BID) plus standard supportive care versus supportive care alone. The primary endpoint ...[more]

PMID: 33212256

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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: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:Rationale & objectiveIndividuals with chronic kidney disease frequently suffer from chronic kidney disease-associated pruritus (CKD-aP), impacting sleep quality and quality of life (QoL) and increasing the likelihood of depression. Difelikefalin is a kappa-opioid receptor agonist recently approved in the United States for the treatment of moderate-to-severe CKD-aP in hemodialysis patients. Study 3105 was conducted to further assess the safety of difelikefalin and the effects on pruritus and QoL.Study designOpen-label, multicenter, single-arm intervention trial.Setting & participantsMaintenance hemodialysis patients with moderate-to-severe CKD-aP at enrollment.InterventionIntravenous difelikefalin 0.5 μg/kg after each hemodialysis session for 12 weeks.OutcomesThe primary outcome was safety of difelikefalin. Secondary outcomes included: effectiveness of reducing itch intensity, assessed by the Worst Itching Intensity Numerical Rating Scale (WI-NRS); improving itch-related QoL, assessed with 5-D itch and Skindex-10 scales; and improvement of sleep, assessed with the Sleep Quality Numerial Rating Scale. Clinically meaningful thresholds for improvement in itch and QoL were previously established in this population.ResultsAmong 222 participants with baseline WI-NRS ≥5, mean [standard deviation] WI-NRS was 7.6 [1.3], mean age 58 years, 55% were male, and mean dialysis duration was 5.9 years; 197 participants (89%) completed treatment. Treatment-related treatment-emergent adverse events were reported in 16 participants (7.2%); those most commonly reported were somnolence (1.8%), hypoesthesia (1.4%), nausea (0.9%), and dizziness (0.9%). No deaths or serious treatment-emergent adverse events were considered treatment-related. Clinically meaningful reduction in itch intensity (≥3-point improvement) was reported by 74% of participants, with 70% and 63% also reporting a clinically relevant improvement in QoL as measured by 5-D itch and Skindex-10. Sleep quality improvement (≥3-point reduction on the Numerical Rating Scale) was reported in 66% of participants.LimitationsNo placebo control group.ConclusionsDifelikefalin was well tolerated, and treatment was associated with clinically meaningful improvements in itch intensity and itch-related QoL measures as well as improvements in sleep quality among individuals receiving hemodialysis who had moderate-to-severe CKD-aP, providing important insights into expected real-world effectiveness.FundingCara Therapeutics.Trial registrationNCT03998163.

Project description:ObjectiveTo assess the efficacy and safety of hydroxychloroquine plus standard of care compared with standard of care alone in adults with coronavirus disease 2019 (covid-19).DesignMulticentre, open label, randomised controlled trial.Setting16 government designated covid-19 treatment centres in China, 11 to 29 February 2020.Participants150 patients admitted to hospital with laboratory confirmed covid-19 were included in the intention to treat analysis (75 patients assigned to hydroxychloroquine plus standard of care, 75 to standard of care alone).InterventionsHydroxychloroquine administrated at a loading dose of 1200 mg daily for three days followed by a maintenance dose of 800 mg daily (total treatment duration: two or three weeks for patients with mild to moderate or severe disease, respectively).Main outcome measureNegative conversion of severe acute respiratory syndrome coronavirus 2 by 28 days, analysed according to the intention to treat principle. Adverse events were analysed in the safety population in which hydroxychloroquine recipients were participants who received at least one dose of hydroxychloroquine and hydroxychloroquine non-recipients were those managed with standard of care alone.ResultsOf 150 patients, 148 had mild to moderate disease and two had severe disease. The mean duration from symptom onset to randomisation was 16.6 (SD 10.5; range 3-41) days. A total of 109 (73%) patients (56 standard of care; 53 standard of care plus hydroxychloroquine) had negative conversion well before 28 days, and the remaining 41 (27%) patients (19 standard of care; 22 standard of care plus hydroxychloroquine) were censored as they did not reach negative conversion of virus. The probability of negative conversion by 28 days in the standard of care plus hydroxychloroquine group was 85.4% (95% confidence interval 73.8% to 93.8%), similar to that in the standard of care group (81.3%, 71.2% to 89.6%). The difference between groups was 4.1% (95% confidence interval -10.3% to 18.5%). In the safety population, adverse events were recorded in 7/80 (9%) hydroxychloroquine non-recipients and in 21/70 (30%) hydroxychloroquine recipients. The most common adverse event in the hydroxychloroquine recipients was diarrhoea, reported in 7/70 (10%) patients. Two hydroxychloroquine recipients reported serious adverse events.ConclusionsAdministration of hydroxychloroquine did not result in a significantly higher probability of negative conversion than standard of care alone in patients admitted to hospital with mainly persistent mild to moderate covid-19. Adverse events were higher in hydroxychloroquine recipients than in non-recipients.Trial registrationChiCTR2000029868.

Dataset Information

Efficacy and safety of favipiravir, an oral RNA-dependent RNA polymerase inhibitor, in mild-to-moderate COVID-19: A randomized, comparative, open-label, multicenter, phase 3 clinical trial.

Objective

Methods

Results

Conclusion

Publications

Efficacy and safety of favipiravir, an oral RNA-dependent RNA polymerase inhibitor, in mild-to-moderate COVID-19: A randomized, comparative, open-label, multicenter, phase 3 clinical trial.

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