Efficacy and safety of sofosbuvir/velpatasvir versus the standard of care in adults hospitalized with COVID-19: a single-centre, randomized controlled trial.

OBJECTIVES: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for the COVID-19 pandemic. The majority of patients experience asymptomatic to mild self-limited disease, but some cases progress to respiratory and multi-organ failure. However, so far, no approved antiviral therapy has been available for treatment of COVID-19. Sofosbuvir/velpatasvir (SOF/VEL) is an approved anti-HCV drug that is capable of suppressing other families of positive-sense RNA viruses with conserved polymerase and may be effective against SARS-CoV-2. This study was conducted to evaluate the efficacy of the SOF/VEL combination in addition to the national standard of care versus the national standard of care alone (hydroxychloroquine and lopinavir/ritonavir as well as supportive care) in patients with moderate to severe COVID-19 infection. METHODS: This single-centre, randomized, open-labelled, prospective clinical trial was done in patients with moderate to severe COVID-19 admitted to Farabi Hospital in Kermanshah Province, Iran. Eligible patients were randomly assigned in a 1:1 ratio to the SOF/VEL arm (SOF/VEL plus the national standard of care) or the control arm (the national standard of care alone). The main outcome of the study was the mortality on Day 28 after randomization. Secondary outcomes were time from the start of medication to clinical improvement, hospital length of stay, need for mechanical ventilation, duration of mechanical ventilation and conversion of RT-PCR results from positive to negative from the time of randomization to discharge. Adverse events were evaluated in all patients who started their assigned treatment. RESULTS: Between 11 April and 8 June 2020, 80 patients were recruited and randomly assigned into the SOF/VEL (n = 40) and control (n = 40) arms. The primary outcome was not significantly different between the two arms (P = 1.00). Secondary outcomes, including time to clinical improvement, hospital length of stay, need for mechanical ventilation, duration of mechanical ventilation and RT-PCR conversion, were not significantly different between arms either (P > 0.05). SOF/VEL treatment and the national standard of care were tolerated similarly. CONCLUSIONS: Although treatment with SOF/VEL was safe, adding SOF/VEL to the standard of care did not improve the clinical status or reduce mortality in patients with moderate to severe COVID-19. However, larger randomized clinical trials including more parameters are needed for accurate estimation of the efficacy of SOF/VEL.

Efficacy and safety of sofosbuvir/ ledipasvir in treatment of patients with COVID-19; A randomized clinical trial.

BACKGROUND: There is no study regarding the use of SOF/LDP in treatment of COVID-19.  Objectives: In this study, the efficacy and safety of SOF/LDP were assessed in treatment of patients with mild to moderate COVID-19. METHODS: Among an open-label randomized clinical trial, 82 patients with mild to moderated COVID-19 were assigned to receive either SOF/LDP 400/100 mg daily plus the standard of care (SOF/LDP group, n=42) or the standard of care alone (control group, n=40) for 10 days. Time to clinical response, rate of clinical response, duration of hospital and ICU stay and 14-day mortality were assessed. RESULTS: Clinical response occurred in 91.46% of patients. Although rates of clinical response were comparable between the groups but it occurred faster in the SOF/LDP group than the control group (2 vs. 4 days respectively, P= 0.02). Supportive cares were provided in the medical wards for most patients but 17.07% of patients were transferred to ICU during the hospitalization course. However, durations of hospital and ICU stay were comparable between the groups.  14--day mortality rate was 7.14% and 7.5% in the SOF/ LDP and control groups respectively. No adverse effects leading to drug discontinuation occurred. Gastrointestinal events (nausea, vomiting and diarrhea) were the most common side effects (15.85%). CONCLUSION: Added to the standard of care, SOF/LDP accelerated time to the clinical response. However, rate of clinical response, duration of hospital and ICU stay and 14-day mortality were not different. No significant adverse event was detected.  More randomized clinical trials with larger sample sizes are needed to confirm the efficacy and safety of SOF/LDP in the treatment of COVID-19.