Efficacy and Safety of a Phytopharmaceutical Drug Derived from <italic>Cocculus hirsutus</italic> in Adults with Moderate COVID-19: a Phase 2, Open-label, Multicenter, Randomized Controlled Trial.

Introduction: There is an urgent need for an effective, oral therapy for COVID-19. Purified aqueous extract of <italic>Cocculus hirsutus</italic> (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.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.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); <italic>p</italic> = 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); <italic>p</italic> = 0.032]. Time to viral clearance and duration of hospitalization were also significantly shorter in the AQCH group (<italic>p</italic> = 0.0002 and <italic>p</italic> = 0.016, respectively). AQCH was well tolerated, with no safety concerns identified.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.Clinical Trials Registry – India (CTRI/2020/05/025397).Methods: There is an urgent need for an effective, oral therapy for COVID-19. Purified aqueous extract of <italic>Cocculus hirsutus</italic> (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.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.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); <italic>p</italic> = 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); <italic>p</italic> = 0.032]. Time to viral clearance and duration of hospitalization were also significantly shorter in the AQCH group (<italic>p</italic> = 0.0002 and <italic>p</italic> = 0.016, respectively). AQCH was well tolerated, with no safety concerns identified.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.Clinical Trials Registry – India (CTRI/2020/05/025397).Results: There is an urgent need for an effective, oral therapy for COVID-19. Purified aqueous extract of <italic>Cocculus hirsutus</italic> (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.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.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); <italic>p</italic> = 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); <italic>p</italic> = 0.032]. Time to viral clearance and duration of hospitalization were also significantly shorter in the AQCH group (<italic>p</italic> = 0.0002 and <italic>p</italic> = 0.016, respectively). AQCH was well tolerated, with no safety concerns identified.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.Clinical Trials Registry – India (CTRI/2020/05/025397).Conclusions: There is an urgent need for an effective, oral therapy for COVID-19. Purified aqueous extract of <italic>Cocculus hirsutus</italic> (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.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.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); <italic>p</italic> = 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); <italic>p</italic> = 0.032]. Time to viral clearance and duration of hospitalization were also significantly shorter in the AQCH group (<italic>p</italic> = 0.0002 and <italic>p</italic> = 0.016, respectively). AQCH was well tolerated, with no safety concerns identified.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.Clinical Trials Registry – India (CTRI/2020/05/025397).Trial Registration: There is an urgent need for an effective, oral therapy for COVID-19. Purified aqueous extract of <italic>Cocculus hirsutus</italic> (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.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.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); <italic>p</italic> = 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); <italic>p</italic> = 0.032]. Time to viral clearance and duration of hospitalization were also significantly shorter in the AQCH group (<italic>p</italic> = 0.0002 and <italic>p</italic> = 0.016, respectively). AQCH was well tolerated, with no safety concerns identified.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.Clinical Trials Registry – India (CTRI/2020/05/025397). [ABSTRACT FROM AUTHOR]