Babak Sayad1,2, Reza Khodarahmi3,4, Farid Najafi5, Ronak Miladi2,6, Zeinab Mohseni Afshar2,6, Feizollah Mansouri2,6, Zohreh Rahimi7, Maria Shirvani2,6, Mehdi Salimi2,6, Siavash Vaziri6,8, Alireza Janbakhsh2,6, Fatemeh Khosravi Shadmani5, Arezoo Bozorgomid1,2, Mohammad Hossein Zamanian2,6, Mandana Afsharian2,6. 1. Infectious Diseases Research Center, Health Institute, Kermanshah University of Medical Sciences, Kermanshah, Iran. 2. Clinical Research Development Center, Imam Reza Hospital, Kermanshah University of Medical Sciences, Kermanshah, Iran. 3. Medical Biology Research Center, Health Technology Institute, Kermanshah University of Medical Sciences, Kermanshah, Iran. 4. Department of Pharmacognosy and Biotechnology, Faculty of Pharmacy, Kermanshah University of Medical Sciences, Kermanshah, Iran. 5. Research Center for Environmental Determinants of Health, Health Institute, Kermanshah University of Medical Sciences, Kermanshah, Iran. 6. Department of Infectious Disease, School of Medicine, Kermanshah University of Medical Sciences, Kermanshah, Iran. 7. Department of Clinical Biochemistry, School of Medicine, Kermanshah University of Medical Sciences, Kermanshah, Iran. 8. Clinical Research Development Center, Imam Khomeini and Mohammad Kermanshahi and Farabi Hospitals, Kermanshah University of Medical Sciences, Kermanshah, Iran.
Abstract
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.
RCT Entities:
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-19infection. 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.