Evaluation of the effect of sofosbuvir and daclatasvir in hospitalized COVID-19 patients: a randomized double-blind clinical trial (DISCOVER)
Authors: Mobarak Sara , Salasi Mehdi , Hormati Ahmad , Khodadadi Javad , Ziaee Masood , Abedi Farshid , Ebrahimzadeh Azadeh , Azarkar Zohreh , Mansour-Ghanaei Fariborz , Joukar Farahnaz , Yeganeh Sara , Yaghubi Kalurazi Tofigh , Naghipour Mohammadreza , Mehrabi Zeinab , Bahadori Amir Reza , Yaghoubi Shoeleh , Moslemi Rohollah , Abbaspour Kasgari Hamideh , Fakheri Hafez , Moghimi Minoo , Shabani Amir Mohammad , Nekoukar Zahra , Babamahmoodi Farhang , Davoudi Badabi Ali Reza , Davoodi Lotfollah , Hassaniazad Mehdi , Barahimi Elham , Tousi Abdolali , Sadeghi Anahita , Hosamirudsari Hadiseh , Ali Asgari Ali , Abdollahi Mohammad , Anushiravani Amir , Shabani Minoosh , Shokouhi Shervin , Khajavirad Nasim , Salehi Mohammadreza , Dehghan Manshadi Seyed Ali , Mousavi Hashem , Zolfaghari Farnaz , Azimi Elmira , Zeinali Aida , Akbarpour Elham , Merat Dorsa , Eslami Gholamali , Mousaviasl Sajedeh , Sayar Sara , Radmanesh Esmat , Ebrahimzadeh Mona , Arizavi Zahra , Jelvay Saeed , Salmanzadeh Shokrollah , Esmaeilian Hani , Mobarak Morteza , Karimi Jalal , Poormontaseri Zahra , Hasooni Bahrini Nasrollah , Bonyadi Atefeh , Dehghani Fatemeh , Mirzaei Hadi , Noori Jangi Masoome , Pourmasoomi Hossein , Rezaie Keikhaie Lili , Afshari Mahdi , Nateghi Baygi Alireza , Nateghi Baygi Helia , Levi Jacob , McCann Kaitlyn , Wentzel Hannah , Simmons Bryony , Hill Andrew , Merat Shahin 
Published: November 2021

Abstract

Background
The combination of sofosbuvir and daclatasvir has shown preliminary efficacy for hospitalized patients with COVID-19 in four open-label studies with small sample sizes. This larger trial aimed to assess if the addition of sofosbuvir/daclatasvir to standard care improved clinical outcomes in hospitalized patients with COVID-19.

Methods
This was a placebo-controlled, double-blind, randomized clinical trial in adults hospitalized with COVID-19 at 19 hospitals in Iran. Patients were randomized to oral sofosbuvir/daclatasvir 400/60 mg once-daily or placebo in addition to standard of care. Patients were included if they had positive PCR or diagnostic chest CT, O2 saturation &lt;95% and compatible symptoms. The primary outcome was hospital discharge within 10 days of randomization. Secondary outcomes included mortality and time to clinical events. The trial is registered on the Iran Registry of Clinical Trials under IRCT20200624047908N1.

Results
Between July and October 2020, 1083 patients were randomized to either the sofosbuvir/daclatasvir arm (n = 541) or the placebo arm (n = 542). No significant difference was observed in the primary outcome of hospital discharge within 10 days, which was achieved by 415/541 (77%) in the sofosbuvir/daclatasvir arm and 411/542 (76%) in the placebo arm [risk ratio (RR) 1.01, 95% CI 0.95–1.08, P = 0.734]. In-hospital mortality was 60/541 (11%) in the sofosbuvir/daclatasvir arm versus 55/542 (10%) in the placebo arm (RR 1.09, 95% CI 0.77–1.54, P = 0.615). No differences were observed in time to hospital discharge or time to in-hospital mortality.

Conclusions
We observed no significant effect of sofosbuvir/daclatasvir versus placebo on hospital discharge or survival in hospitalized COVID-19 patients.