Experimental Treatment with Favipiravir for COVID-19: An Open-Label Control Study

Abstract

a b s t r a c tAn outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and its caused coronavirus disease 2019 has been reported in China since December 2019. More than 16% of patients developed acute respiratory distress syndrome, and the fatality ratio was about 1%-2%. No specific treatment has been reported. Herein, we examine the effects of Favipiravir (FPV) versus Lopinavir (LPV)/ritonavir (RTV) for the treatment of COVID-19. Patients with laboratory-confirmed COVID-19 who received oral FPV (Day 1: 1600 mg twice daily; Days 2-14: 600 mg twice daily) plus interferon (IFN)-a by aerosol inhalation (5 million U twice daily) were included in the FPV arm of this study, whereas patients who were treated with LPV/RTV (Days 1-14: 400 mg/100 mg twice daily) plus IFN-a by aerosol inhalation (5 million U twice daily) were included in the control arm. Changes in chest computed tomography (CT), viral clearance, and drug safety were compared between the two groups. For the 35 patients enrolled in the FPV arm and the 45 patients in the control arm, all baseline characteristics were comparable between the two arms. A shorter viral clearance time was found for the FPV arm versus the control arm (median (interquartile range, IQR), 4 (2.5-9) d versus 11 (8-13) d, P < 0.001). The FPV arm also showed significant improvement in chest imaging compared with the control arm, with an improvement rate of 91.43% versus 62.22% (P = 0.004). After adjustment for potential confounders, the FPV arm also showed a significantly higher improvement rate in chest imaging. Multivariable Cox regression showed that FPV was independently associated with faster viral clearance. In addition, fewer adverse reactions were found in the FPV arm than in the control arm. In this open-label nonrandomized control study, FPV showed significantly better treatment effects on COVID-19 in terms of disease progression and viral clearance; if causal, these results should be important information for establishing standard treatment guidelines to combat the SARS-CoV-2 infection.

Favipiravir: Pharmacokinetics and Concerns About Clinical Trials for 2019‐nCoV Infection

“…A clinical trial to evaluate the safety and efficacy of favipiravir in the treatment of COVID-19 (ChiCTR2000029600) was conducted in Shenzhen, with 80 patients recruited. 11 The results showed that the 35 patients in the favipiravir arm demonstrated significantly shorter viral clearance time as compared with the 45 patients in the control arm (median 4 days vs. 11 days). X-ray examinations confirmed a higher rate of improvement in chest imaging in the favipiravir arm (91.43% vs. 62%).…”

COVID-19 Pandemic: an Overview of epidemiology, pathogenesis, Diagnostics and Potential Vaccines and Therapeutics

“…For example, 199 patients in a clinical future science group www.future-science.com study conducted in Jin Yin-Tan Hospital, received a supportive therapy of supplemental oxygen, noninvasive and invasive ventilation, antibiotics, vasopressor support, renal-replacement therapy and extracorporeal membrane oxygenation (ECMO) [72]. Another clinical study at the national clinical research center for infectious diseases (the Third People's Hospital of Shenzhen), Shenzhen, China, has reported the use of oxygen inhalation, oral or intravenous rehydration therapy, electrolyte correction, antipyretics, analgesics and antiemetic drugs as supportive therapy for the patient [73]. Another example of supportive care is what is given to the first diagnosed case of SARS-CoV-2 in Washington, USA.…”

“…It blocks the replication of several viruses other than influenza. [73]. Therefore, FPV stands as a promising agent in the management of SARS-CoV-2.…”

Treatment of patients with nonsevere and severe coronavirus disease 2019: an evidence-based guideline

“…With regard to favipiravir, an RCT 25 in 236 patients with mixedseverity COVID-19 suggested, in comparison with umifenovir, a possible higher incidence of recovery at day 7, but because of risk of bias, imprecision and indirectness, the evidence was only very low quality (Appendix 3). 22 One observational study 26 in 80 patients with nonsevere COVID-19 provides very low-quality evidence that favipiravir may increase viral clearance at day 7 relative to lopinavir-ritonavir. Symptomatic benefit outcomes from patients with nonsevere disease for other agents were unavailable.…”