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Efficacy and Safety of Sofosbuvir/Daclatasvir in the Treatment of COVID-19: A Randomized, Controlled Study

20 Pages Posted: 6 Oct 2020

See all articles by Mostafa Yakoot

Mostafa Yakoot

Green Clinic and Research Center

Basem Eysa

National Hepatology and Tropical Medicine Research Institute (NHTMRI)

Essam Gouda

Alexandria University - Chest Diseases Department

Andrew Hill

University of Liverpool - Department of Translational Medicine

Sherine A. Helmy

Pharco Corporate

Mahmoud R. Elsayed

Alexandria University - Chest Diseases Department

Ambar Qavi

University of Liverpool

Kaitlyn McCann

University of Liverpool

Ola Elrouby

Pharco Corporate

Amal Mohamed

National Hepatology and Tropical Medicine Research Institute (NHTMRI)

Ehab Reyad

National Hepatology and Tropical Medicine Research Institute (NHTMRI)

Mohamed M. Fawzi

National Hepatology and Tropical Medicine Research Institute (NHTMRI)

Safaa Elmandouh

National Hepatology and Tropical Medicine Research Institute (NHTMRI)

Wessam Abdellatif

National Hepatology and Tropical Medicine Research Institute (NHTMRI)

Ahmed A. Zidan

National Hepatology and Tropical Medicine Research Institute (NHTMRI)

Abd-Elmoniem Adel

National Hepatology and Tropical Medicine Research Institute (NHTMRI)

Mohamad Hassany

National Hepatology and Tropical Medicine Research Institute (NHTMRI)

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Abstract

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.

Keywords: COVID-19, Drug therapy, Sofosbuvir, Daclatasvir, Randomized controlled study

Suggested Citation

Yakoot, Mostafa and Eysa, Basem and Gouda, Essam and Hill, Andrew and Helmy, Sherine A. and Elsayed, Mahmoud R. and Qavi, Ambar and McCann, Kaitlyn and Elrouby, Ola and Mohamed, Amal and Reyad, Ehab and Fawzi, Mohamed M. and Elmandouh, Safaa and Abdellatif, Wessam and Zidan, Ahmed A. and Adel, Abd-Elmoniem and Hassany, Mohamad, Efficacy and Safety of Sofosbuvir/Daclatasvir in the Treatment of COVID-19: A Randomized, Controlled Study. Available at SSRN: https://ssrn.com/abstract=3705289 or http://dx.doi.org/10.2139/ssrn.3705289

Mostafa Yakoot (Contact Author)

Green Clinic and Research Center ( email )

Alexandria, 21121
Egypt
+201223927561 (Phone)

Basem Eysa

National Hepatology and Tropical Medicine Research Institute (NHTMRI) ( email )

Egypt

Essam Gouda

Alexandria University - Chest Diseases Department ( email )

El-Guish Road
El-Shatby
Alexandria, 21321
Egypt

Andrew Hill

University of Liverpool - Department of Translational Medicine

Chatham Street
Liverpool, L69 7ZA
United Kingdom

Sherine A. Helmy

Pharco Corporate ( email )

Mahmoud R. Elsayed

Alexandria University - Chest Diseases Department

El-Guish Road
El-Shatby
Alexandria, 21321
Egypt

Ambar Qavi

University of Liverpool ( email )

Chatham Street
Liverpool, L69 7ZA
United Kingdom

Kaitlyn McCann

University of Liverpool ( email )

Chatham Street
Liverpool, L69 7ZA
United Kingdom

Ola Elrouby

Pharco Corporate ( email )

Amal Mohamed

National Hepatology and Tropical Medicine Research Institute (NHTMRI)

Egypt

Ehab Reyad

National Hepatology and Tropical Medicine Research Institute (NHTMRI) ( email )

Egypt

Mohamed M. Fawzi

National Hepatology and Tropical Medicine Research Institute (NHTMRI) ( email )

Egypt

Safaa Elmandouh

National Hepatology and Tropical Medicine Research Institute (NHTMRI) ( email )

Egypt

Wessam Abdellatif

National Hepatology and Tropical Medicine Research Institute (NHTMRI) ( email )

Egypt

Ahmed A. Zidan

National Hepatology and Tropical Medicine Research Institute (NHTMRI)

Egypt

Abd-Elmoniem Adel

National Hepatology and Tropical Medicine Research Institute (NHTMRI) ( email )

Egypt

Mohamad Hassany

National Hepatology and Tropical Medicine Research Institute (NHTMRI) ( email )

Egypt

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