Randomized controlled open label trial on the use of favipiravir combined with inhaled interferon beta-1b in hospitalized patients with moderate to severe COVID-19 pneumonia.

OBJECTIVE: To evaluate the therapeutic effectiveness of favipiravir combined with inhaled interferon beta-1b in adult patients hospitalized with moderate to severe COVID-19 pneumonia. METHODS: A randomized, open-label controlled trial of oral favipiravir in adults hospitalized with moderate to severe COVID-19 pneumonia from June 22nd 2020 to August 13th 2020 was conducted. Patients were randomly assigned to receive either a combination of favipiravir with interferon beta-1b by inhalation aerosol or hydroxychloroquine (HCQ). The outcome endpoints included improvement in inflammatory markers, lower length of hospital stay (LOS), discharges and lower overall 14-day mortality. RESULTS: A total of 89 patients underwent randomization with 49% (n = 44) assigned to favipiravir and 51% (n = 45) assigned HCQ. The overall mean age was 55 ± 14 years and 58% (n = 52) were males. There were no significant differences in the inflammatory biomarkers at hospital discharge between the two groups; C-reactive protein (p = 0.413), ferritin (p = 0.968), lactate dehydrogenase (p = 0.259) and interleukin 6 (p = 0.410). There were also no significant differences between the two groups with regards to the overall LOS (7 vs 7 days; p = 0.948), transfers to the ICU (18.2% vs 17.8%; p = 0.960), discharges (65.9% vs 68.9%; p = 0.764) and overall mortality (11.4% vs 13.3%; p = 0.778). CONCLUSIONS: No differences in clinical outcomes were found between favipiravir plus inhaled interferon beta-1b and hydroxychloroquine in adults hospitalized with moderate to severe COVID-19 pneumonia.

Interferon ß-1b in treatment of severe COVID-19: A randomized clinical trial.

In this study, efficacy and safety of interferon (IFN) ß-1b in the treatment of patients with severe COVID-19 were evaluated. Among an open-label, randomized clinical trial, adult patients (≥18 years old) with severe COVID-19 were randomly assigned (1:1) to the IFN group or the control group. Patients in the IFN group received IFN ß-1b (250 mcg subcutaneously every other day for two consecutive weeks) along with the national protocol medications while in the control group, patients received only the national protocol medications (lopinavir/ritonavir or atazanavir/ritonavir plus hydroxychloroquine for 7-10 days). The primary outcome of the study was time to clinical improvement. Secondary outcomes were in-hospital complications and 28-daymortality. Between April 20 and May 20, 2020, 80 patients were enrolled and finally 33 patients in each group completed the study. Time to clinical improvment in the IFN group was significantly shorter than the control group ([9(6-10) vs. 11(9-15) days respectively, p = 0.002, HR = 2.30; 95% CI: 1.33-3.39]). At day 14, the percentage of discharged patients was 78.79% and 54.55% in the IFN and control groups respectively (OR = 3.09; 95% CI: 1.05-9.11, p = 0.03). ICU admission rate in the control group was significantly higher than the IFN group (66.66% vs. 42.42%, p = 0.04). The duration of hospitalization and ICU stay were not significantly different between the groups All-cause 28-day mortality was 6.06% and 18.18% in the IFN and control groups respectively (p = 0.12). IFN ß-1b was effective in shortening the time to clinical improvement without serious adverse events in patients with severe COVID-19. Furthermore, admission in ICU and need for invasive mechanical ventilation decreased following administration of IFN ß-1b. Although 28-day mortality was lower in the IFN group, further randomized clinical trials with large sample size are needed for exact estimation of survival benefit of IFN ß-1b.