Current best evidence for clinical care (more info)
BACKGROUND: Currently no effective antiviral therapy has been found to treat COVID-19. The aim of this trial was to assess if the addition of sofosbuvir and daclatasvir improved clinical outcomes in patients with moderate or severe COVID-19.
METHODS: This was an open-label, multicentre, randomized controlled clinical trial in adults with moderate or severe COVID-19 admitted to four university hospitals in Iran. Patients were randomized into a treatment arm receiving sofosbuvir and daclatasvir plus standard care, or a control arm receiving standard care alone. The primary endpoint was clinical recovery within 14 days of treatment. The study is registered with IRCT.ir under registration number IRCT20200128046294N2.
RESULTS: Between 26 March and 26 April 2020, 66 patients were recruited and allocated to either the treatment arm (n = 33) or the control arm (n = 33). Clinical recovery within 14 days was achieved by 29/33 (88%) in the treatment arm and 22/33 (67%) in the control arm (P = 0.076). The treatment arm had a significantly shorter median duration of hospitalization [6 days (IQR 4-8)] than the control group [8 days (IQR 5-13)]; P = 0.029. Cumulative incidence of hospital discharge was significantly higher in the treatment arm versus the control (Gray's P = 0.041). Three patients died in the treatment arm and five in the control arm. No serious adverse events were reported.
CONCLUSIONS: The addition of sofosbuvir and daclatasvir to standard care significantly reduced the duration of hospital stay compared with standard care alone. Although fewer deaths were observed in the treatment arm, this was not statistically significant. Conducting larger scale trials seems prudent.
| Discipline / Specialty Area | Score |
|---|---|
| Hospital Doctor/Hospitalists | |
| Internal Medicine | |
| Respirology/Pulmonology | |
| Intensivist/Critical Care | |
| Infectious Disease | |
In this randomized trial, patients with documented COVID-19 are randomized to receiving 2 hepatitis C medications that theoretically should affect COVID-19 replication. During the context of the trial, hydroxychloroquine and lopinavir/ritonavir were best standard of care; these were both to used variably in this trial. It is a small trial with only 33 patients per arm; only 10 of the 66 patients required mechanical ventilation, so they may have been less sick. Corticosteroids, now believed to be beneficial, were used in 20 (more in the intervention arm). There was no statistical difference in death, but trends favored the intervention drug. It is good to know that there is something else to study in COVID-19; this finding should be replicated and compared to best available medications before it should become our go-to drug, but this combination deserves further study.
This is a small study comparing the addition of sofosbuvir/ daclatasvir combination to hydroxychloroquine in moderate to severe SARS-CoV-2 infection. These drugs work in hepatitis C by acting on the RNA-dependent RNA polymerase and it was hoped, despite lack of convincing in vitro evidence, that they may have an effect in COVID-19. 66 patients were randomized to either get this drug combinaton or not but all received hydroxychloroquine. Some also received lopinavir/ritonavir in a non-systematic way. Although the authors claim some small benefit from the sofosbuvir/daclatasvir combination, this study is so flawed by the lack of a placebo, the confounding effect of other antivirals and the presence of hydroxychloroquine to say nothing of the small size of the study. Drawing any meaningful conclusion is aggressive. Clinicians need to be aware of this study because of its appearance in the lay press.
There is a small sample size. It's just promising.