ABSTRACT
Background: COVID-19 is a pandemic disease caused by SARS-CoV-2, which is an RNA virus similar to HCV in the replication process. Sofosbuvir/ledipasvir is an approved drug by the FDA to treat HCV infection. This study investigates the efficacy of Sofosbuvir/ledipasvir as a treatment for patients with moderate COVID-19 infection.. Methods: This is a single-blinded parallel-randomized controlled trial. The participants were randomized equally into the intervention group received Sofosbuvir/ledipasvir (S.L. group), and the control group received Oseltamivir, Hydroxychloroquine, and Azithromycin (OCH group). The primary outcomes were the cure rate over time and the incidence of serious adverse events. The secondary outcomes included the laboratory findings. Results: Two hundred and fifty patients were divided equally into each group. Both groups were similar regarding gender, but age was higher in the S.L. group (p=0.001). In the S.L. group, 89 (71.2%) patients were cured, while only 51 (40.8%) patients were cured in the OCH group. The cure rate was significantly higher in the S.L. group (RR=1.75, p<0.001). Kaplan-Meir plot showed a considerably higher cure over time in the S.L. group (Log-rank test, p=0.032). There were no deaths in the S.L. group, but there were six deaths (4.8%) in the OCH group (RR=0.08, p=0.013). Seven patients (5.6%) in the S.L. group and six patients (4.8%) in the OCH group were admitted to ICU (RR=1.17, P=0.776). There was no significant difference between treatment groups regarding Total Leukocyte Count, Neutrophils count, Lymph, Alanine transaminase, and Urea. Conclusion: Sofosbuvir/ledipasvir is suggestive of being effective in treating patients with moderate COVID-19 infection. Further studies are needed to compare Sofosbuvir/ledipasvir with the new treatment protocols.
Subject(s)
COVID-19 , Hepatitis C , DiseaseABSTRACT
BACKGROUND: Data from molecular docking, in-vitro experiments and 2 published small clinical studies suggested a potential therapeutic benefit for the anti-hepatitis C drugs, sofosbuvir (SOF) and daclatasvir (DCV), to repurpose for the treatment of COVID-19. We planned this study to evaluate efficacy and safety of dual SOF/DCV as add-on treatment to the standard of care (SOC) in patients with COVID-19, initially hospitalized to a non-intensive care setting.METHODS: Eighty nine consecutive eligible patients presenting to a single center in Cairo were included in the study and randomly assigned to two treatment groups. The experimental group was treated with the SOC therapy (as per the Egyptian ministry of health protocol) in addition to one 400 mg tablet SOF and one 60 mg DCV daily for 10 days; while the control group was treated with the SOC therapy alone. Baseline clinical, laboratory and imaging data were measured and followed up for 21 days. Data were compared between the two treatment groups.FINDINGS: The proportion of cumulative clinical recovery in the experimental group at day 21 was numerically greater than the control group (40/44 (91%; CI: 78.8-96.4%) versus 35/45 (77.8%; 63.7-87.5%)). The Hazard Ratio (HR) for time to clinical recovery adjusted for baseline severity by a Cox-regression model was statistically significant: HR: 1.59 (CI: 1.001-2.5), signifying nearly 1.6 times higher probability of clinical recovery in the experimental group than the control at any time point during the study. Concordantly, the experimental group also showed trends to greater numerical improvement in other efficacy endpoints including the mean 8 points ordinal scale score, the mean severity of lung lesions score and the case fatality rate (4.5% versus 11.1%) than the control group. All these effects, though did not reach statistical significance at the study sample size, but being all concordant with the HR, they support the study concept. No serious or severe adverse events were reported in both groups and the treatment was well tolerated.INTERPRETATION: This study provides support to the potential benefits and safety of sofosbuvir combined with daclatasvir in the treatment of COVID-19. It is hoped to encourage further large sized multinational studies to confirm these encouraging results.Trial Registration: The study protocol was registered in the German clinical trial database repository (DRKS00022203) before the study initiation.Funding Statement: This study was funded by Pharco Corporate.Declaration of Interests: SH and OE are employees of Pharco, SH holds stock in Pharco. MY, AH conducted clinical studies and provided consultations for Pharco. Others have nothing to declare. Ethics Approval Statement: The study protocol was reviewed and approved by the Research Ethics Committee of Faculty of Medicine, Alexandria University (IRB00007555) and the Central Egyptian Ministry of Health and People Research Ethics Committee according to the Declaration of Helsinki. All subjects gave written informed consent before any treatment interventions were performed.