Favipiravir Versus Arbidol for Clinical Recovery Rate in Moderate and Severe Adult COVID-19 Patients: A Prospective, Multicenter, Open-Label, Randomized Controlled Clinical Trial
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Abstract
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.
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SciScore for 10.1101/2020.03.17.20037432: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Institutional Review Board Statement Consent: Patients: Patients were assessed for eligibility on the basis of: (1) aged 18 years or older; (2) voluntarily provided informed consent; (3) initial symptoms were within 12 days; (4) Diagnosed as COVID-19 pneumonia.
IACUC: The study was approved by the Institutional Ethics Committee (No. 2020040) (additional details in Protocol/SAP).Randomization Study design: The study was designed as a prospective, randomized, controlled, open-label multicenter trial (Figure 1) conducted from Feb. 20 to Mar. 1, 2020 in three hospitals (Zhonghan Hospital of Wuhan University (ZNWU), Leishenshan Hospital (LSS) and the Third Hospital of Hubei Province (HBTH)) of Wuhan, … SciScore for 10.1101/2020.03.17.20037432: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Institutional Review Board Statement Consent: Patients: Patients were assessed for eligibility on the basis of: (1) aged 18 years or older; (2) voluntarily provided informed consent; (3) initial symptoms were within 12 days; (4) Diagnosed as COVID-19 pneumonia.
IACUC: The study was approved by the Institutional Ethics Committee (No. 2020040) (additional details in Protocol/SAP).Randomization Study design: The study was designed as a prospective, randomized, controlled, open-label multicenter trial (Figure 1) conducted from Feb. 20 to Mar. 1, 2020 in three hospitals (Zhonghan Hospital of Wuhan University (ZNWU), Leishenshan Hospital (LSS) and the Third Hospital of Hubei Province (HBTH)) of Wuhan, Hubei, China. Blinding not detected. Power Analysis not detected. Sex as a biological variable Hence, male and female adult patients with clinically confirmed COVID-19 including moderate, severe or critical types of COVID-19 were eligible. Table 2: Resources
No key resources detected.
Results from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).
Results from LimitationRecognizer: We detected the following sentences addressing limitations in the study:Our trial has several limitations. Firstly, for COVID-19, there is no clinically proven effective antiviral drug to serve as the control arm. Although Chinese guideline had recommended several options including Arbidol,11 no RCT results on these drugs were reported. Arbidol was widely used by Chinese doctors in the beginning stage of this epidemic of COVID-19 (Jan. 1-30, 2020) based on in vitro evidence.12 For ethical reasons, we chose Arbidol for the control arm. Secondly, observation time frame was limited due to the urgency of this epidemic. For the same reason, no relapse (including nucleic acid conversion, pyrexia, cough, or pneumonia progress by radiology) tracking were performed for the discharged patients. Thirdly, in the inclusion criteria, we did not force positive nucleic acid test as a necessity. The accuracy of nucleic acid assay was limited, which might due to multiple reasons including previous treatment, latency of onset, sampling method, biological specimen characteristics. This particular accuracy problem was a known issue among clinical practitioners across the world. It was estimated that the assay might have at most 30%-50% of sensitivity for patients in early stage of the disease, whilst contact history, clinical manifestations, radiology evidences, and lab results including leukopenia and lymphopenia could be confirmatory for these nucleic-acid-negative pneumonia patients. In the Chinese guideline,11 patients meeting these criteria were considered as wi...
Results from TrialIdentifier: No clinical trial numbers were referenced.
Results from Barzooka: We did not find any issues relating to the usage of bar graphs.
Results from JetFighter: We did not find any issues relating to colormaps.
Results from rtransparent:- Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
- Thank you for including a funding statement. Authors are encouraged to include this statement when submitting to a journal.
- No protocol registration statement was detected.
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