ABSTRACT
Background: Oral anti-viral therapies are licensed worldwide in COVID-19 but indications and efficacy rates vary. Aims and Objectives: To evaluate the safety and efficacy of oral favipiravir in patients hospitalised with COVID-19. Method(s): We conducted a multi-centre, open-label, randomised controlled trial of oral favipiravir in patients newly hospitalised with COVID-19, in five centres worldwide. 500 participants were randomised 1:1 to receive oral favipiravir (1800 mg twice daily (BD) for one-day;800 mg BD for nine-days) plus standard care (SC), or SC alone. NCT: 04373733. Result(s): Recruitment was performed between May 2020 and May 2021, with 251 patients randomised to favipiravir and 249 to SC. There was no difference in time to recovery in all patients (HR 1 06;95% CI 0 89-1 27;n=499;p=0.52). A faster rate of recovery was observed in patients receiving favipiravir under the age of 60 years (HR 1 35;95% CI 1 06-1 72;n=247, p=0 01). A 66 % improvement in mechanical ventilation free survival was evident in patients under 60-years of age (HR 0 34;95% CI 0 13-0 85;n=247, p=0 02). A non-significant 26 % reduction in mortality was observed in patients receiving favipiravir (favipiravir: 26;SC: 34;p=0 24). No significant differences were observed in serious adverse events (SAE) between arms (favipiravir: 36 in 27 patients;SC: 33 in 27 patients). Conclusion(s): Orally administered favipiravir has a beneficial effect on recovery, and mechanical ventilation freesurvival in patients under 60-years of age, hospitalised with COVID-19. Wider evaluation of anti-viral medications and their potential treatment combinations is warranted in patients with COVID-19.
ABSTRACT
Background. There are few real-world data on the use of remdesivir (RDV) looking at timing of initiation in relation to symptom onset and severity of presenting disease. Methods. We conducted multi-country retrospective study of clinical practice and use of RDV in COVID-19 patients. De-identified medical records data were entered into an e-CRF. Primary endpoints were all-cause mortality at day 28 and hospitalization duration. We assessed time from symptom onset to RDV start and re-admission. We included adults with PCR-confirmed symptomatic COVID-19 who were hospitalized after Aug 31, 2020 and received at least 1 dose of RDV. Descriptive analyses were conducted. Kaplan-Meier methods were used to calculate the mortality rate, LogRank test to compare groups defined by severity of disease. Competing risk regression with discharge and death as competing events was used to estimate duration of hospitalization, and Gray's test to compare the groups. Results. 448 patients in 5 countries (12 sites) were included. Demographics are summarized (table) by 3 disease severity groups at baseline: no supplemental oxygen (NSO), low flow oxygen ≤6 L/min (LFO), and high-flow oxygen > 6L/min (HFO). No demographic differences were found between groups except for the higher percentage of cancer/chemotherapy patients in NSO group. Corticosteroids use was HFO 73.6%, LFO 62.7%, NSO 58.0%. Mortality rate was significantly lower in NSO, and LFO groups compared with HFO (6.2%, 10.2%, 23.6%, respectively;Fig1). Median duration of hospitalization was 9 (95%CI 8-10), 9 (8-9), 13 (10-15) days, respectively (Fig2). Median time from first symptom to RDV start was 7 days in all 3 groups. Patients started RDV on day 1 of hospitalization in HFO and LFO and day 2 on NSO groups. And received a 5 day course (median). Readmission within 28-days of discharge was < 5% and similar across all 3 groups. Conclusion. In this real-world cohort of COVID-19 positive hospitalized patients, RDV use was consistent across countries. RDV was started within a median of 7 days from symptom within 2 days of admission and given for a median of 5 days. Higher mortality rate and duration of hospitalization was seen in the HFO group and similar rates seen in the LFO and NSO groups. Readmission was consistently low across all 3 groups.