Evaluation of the efficacy of sofosbuvir plus daclatasvir in combination with ribavirin for hospitalized COVID-19 patients with moderate disease compared with standard care: a single-centre, randomized controlled trial

J Antimicrob Chemother. 2020 Nov 1;75(11):3373-3378. doi: 10.1093/jac/dkaa332.

Abstract

Background: New therapeutic options are urgently needed to tackle the novel coronavirus disease 2019 (COVID-19). Repurposing existing pharmaceuticals provides an immediate treatment opportunity. We assessed the efficacy of sofosbuvir and daclatasvir with ribavirin for treating patients with COVID-19.

Methods: This was a single-centre, randomized controlled trial in adults with moderate COVID-19 admitted to the Ghaem Shahr Razi Hospital in Mazandaran Province, Iran. Patients were randomly assigned to 400 mg sofosbuvir, 60 mg daclatasvir and 1200 mg ribavirin (intervention group) or to standard care (control group). The primary endpoint of this study was length of hospital stay. This study is registered by IRCT.ir under the ID: IRCT20200328046886N1.

Results: Between 20 March 2020 and 8 April 2020, 48 patients were recruited; 24 patients were randomly assigned to the intervention group and 24 to the control group. The median duration of hospital stay was 6 days in both groups (P = 0.398). The number of ICU admissions in the sofosbuvir/daclatasvir/ribavirin group was not significantly lower than the control group (0 versus 4, P = 0.109). There was no difference in the number of deaths between the groups (0 versus 3, P = 0.234). The cumulative incidence of recovery was higher in the sofosbuvir/daclatasvir/ribavirin arm (Gray's P = 0.033).

Conclusions: This randomized trial was too small to make definitive conclusions. There were trends in favour of the sofosbuvir/daclatasvir/ribavirin arm for recovery and lower death rates. However, there was an imbalance in the baseline characteristics between the arms. Larger randomized trials should be conducted to investigate this treatment further.

Publication types

  • Comparative Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Antiviral Agents / administration & dosage*
  • Betacoronavirus*
  • COVID-19
  • Carbamates
  • Coronavirus Infections / diagnosis
  • Coronavirus Infections / drug therapy*
  • Coronavirus Infections / epidemiology
  • Drug Therapy, Combination
  • Female
  • Hospitalization / trends
  • Humans
  • Imidazoles / administration & dosage*
  • Iran / epidemiology
  • Male
  • Middle Aged
  • Pandemics
  • Pneumonia, Viral / diagnosis
  • Pneumonia, Viral / drug therapy*
  • Pneumonia, Viral / epidemiology
  • Pyrrolidines
  • Ribavirin / administration & dosage*
  • SARS-CoV-2
  • Sofosbuvir / administration & dosage*
  • Treatment Outcome
  • Valine / analogs & derivatives

Substances

  • Antiviral Agents
  • Carbamates
  • Imidazoles
  • Pyrrolidines
  • Ribavirin
  • Valine
  • daclatasvir
  • Sofosbuvir