ABSTRACT
Purpose: To evaluate the safety and efficacy of favipiravir, which is prescribed for the treatment of patients with mild-to-moderate coronavirus disease 2019 (COVID-19) in India. Patients and Methods: This was a prospective, open-label, multicenter, single-arm postmarketing study conducted in India. Patients with mild-to-moderate COVID-19 received favipiravir (3600 mg [1800 mg orally twice daily] on the first day, followed by 800 mg orally twice daily, up to a maximum of 14 days) as a part of their treatment. The primary endpoints were to evaluate the safety of favipiravir by assessing the number of adverse events (AEs) and treatment-related AEs. The secondary endpoints were to evaluate the efficacy of favipiravir by assessing time to clinical cure, rate of clinical cure, time to pyrexia resolution, rate of oxygen requirement, and all-cause mortality. Results: A total of 1083 patients were enrolled in this study from December 2020 to June 2021. Adverse events were reported in 129 patients (11.9%), 116 (10.7%) of whom had mild AEs. Dose modification or withdrawal of favipiravir treatment was reported in four patients (0.37%). The median time to clinical cure and pyrexia resolution was 7 and 4 days, respectively. A total of 1036 patients (95.8%) exhibited clinical cure by day 14. Oxygen support was required by 15 patients (1.4%). One death was reported, which was unrelated to favipiravir. Conclusion: In the real-world setting, favipiravir was well-tolerated, and no new safety signals were detected.
ABSTRACT
INTRODUCTION: There is an urgent need for an effective, oral therapy for COVID-19. Purified aqueous extract of Cocculus hirsutus (AQCH) has shown robust antiviral activity in in vitro studies. We aimed to evaluate the efficacy and safety of AQCH plus standard of care in hospitalized patients with moderate COVID-19. METHODS: In an open-label, multicenter, randomized controlled trial conducted in India, eligible patients (aged 18-75 years) were randomized (1:1) to receive AQCH 400 mg orally three times a day plus standard of care (AQCH group) or standard of care alone (control group) for 10 days. Primary endpoint was the proportion of patients showing clinical improvement by day 14. Time to clinical improvement, time to viral clearance, and duration of hospitalization were secondary endpoints. RESULTS: A total of 210 patients were randomized. By day 14 most patients in both groups showed clinical improvement [difference - 0.01 (95% CI - 0.07 to 0.05); p = 1.0]. Median time to clinical improvement was 8 days (IQR 8-11) in the AQCH group versus 11 days (IQR 8-11) in the control group [HR 1.27 (95% CI 0.95-1.71); p = 0.032]. Time to viral clearance and duration of hospitalization were also significantly shorter in the AQCH group (p = 0.0002 and p = 0.016, respectively). AQCH was well tolerated, with no safety concerns identified. CONCLUSIONS: AQCH significantly reduced time to clinical improvement, time to viral clearance, and duration of hospitalization. In a pandemic, this has significant potential to decrease healthcare resource utilization and increase hospital bed availability. Further investigation of the therapeutic potential of AQCH in patients with COVID-19 is warranted. TRIAL REGISTRATION: Clinical Trials Registry - India (CTRI/2020/05/025397).