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

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.

Efficacy of antiviral therapies for COVID-19: a systematic review of randomized controlled trials

“…One study was originally included, but was later retracted due to concerns about data integrity, and thus was excluded [ 42 ]. Antiviral treatments compared in the included studies were umifenovir (Arbidol) [ 25 , 29 , 31 , 47 ], baloxavir marboxil [ 30 ], enisamium [ 50 ], favipiravir [ 25 , 30 , 35 , 40 – 42 , 44 , 45 , 48 , 52 ], lopinavir/ritonavir (LPV/r) [ 24 , 26 , 27 , 29 , 31 , 37 , 38 , 44 , 47 ], remdesivir [ 23 , 34 , 36 , 39 , 51 , 53 ], ribavirin [ 22 ], sofosbuvir/daclatasvir [ 22 , 32 , 33 , 46 , 49 ], sofosbuvir/ledipasvir [ 28 ], sofosbuvir/ravidasvir [ 46 ], and sofosbuvir/velpatasvir [ 43 ]. The study characteristics and baseline patient characteristics are summarized in Table 2 .…”

“…Of the RCTs that used sofosbuvir/daclatasvir, all five reported significantly better results for the treatment group for at least one outcome, although the magnitude of the effect was often small [ 22 , 32 , 33 , 46 , 49 ]. Of the three RCTs that included sofosbuvir combined with drugs other than daclatasvir, none reported significant differences between the treatment and control groups [ 28 , 43 , 46 ].…”

“…They found that sofosbuvir/ledipasvir had a shorter time to clinical improvement (2 [1–3.75]) compared to control (4 [2–5, p = 0.02), but no significant differences in incidence of clinical improvement (p = 0.65), duration of hospital stay (p = 0.98), or 14-day mortality (p = 0.60) between the groups. Sayad et al compared sofosbuvir/velpatasvir to standard of care alone [ 43 ]. They likewise found no difference in 28-day mortality (p = 0.38), time to clinical improvement (HR: 1.2 [95% CI 0.6–2.2], p = 0.30), or conversion to negative RT-PCR tests (p = 0.49).…”

“…However, Roozbeh et al did not observe a difference in symptoms between groups with mild COVID-19 after 7 days of treatment [ 32 ], and there were no mortality benefits observed with sofosbuvir/daclatasvir treatment. Additionally, combinations of sofosbuvir with other drugs similar to daclatasvir did not lead to differences in outcomes compared to standard of care [ 28 , 43 , 46 ]. The fact that sofosbuvir/daclatasvir is available in pill form as opposed to IV (as is the case with remdesivir), its inexpensive price tag (14-day treatment is $4.42 USD) [ 99 ], and its favorable safety profile noted in hepatitis C treatment [ 100 , 101 ] make sofosbuvir/daclatasvir an appealing option, provided its efficacy can be established in larger RCTs.…”

Efficacy and safety of sofosbuvir plus daclatasvir or ravidasvir in patients with COVID‐19: A randomized controlled trial

“…A combination of SOF/velpatasvir was also found ineffective in improving clinical status or reducing mortality rates. 36 So, clinical trials investigating monotherapy versus a combination of antivirals drugs to elucidate this hypothesis are recommended.…”