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Randomized Controlled Trial
. 2022 Feb 23;77(3):758-766.
doi: 10.1093/jac/dkab433.

Evaluation of the effect of sofosbuvir and daclatasvir in hospitalized COVID-19 patients: a randomized double-blind clinical trial (DISCOVER)

Sara Mobarak  1 , Mehdi Salasi  2 , Ahmad Hormati  3   4 , Javad Khodadadi  5 , Masood Ziaee  6 , Farshid Abedi  6 , Azadeh Ebrahimzadeh  6 , Zohreh Azarkar  6 , Fariborz Mansour-Ghanaei  7 , Farahnaz Joukar  7 , Sara Yeganeh  8 , Tofigh Yaghubi Kalurazi  9 , Mohammadreza Naghipour  7 , Zeinab Mehrabi  10 , Amir Reza Bahadori  11 , Shoeleh Yaghoubi  10 , Rohollah Moslemi  12 , Hamideh Abbaspour Kasgari  13 , Hafez Fakheri  14 , Minoo Moghimi  13 , Amir Mohammad Shabani  13 , Zahra Nekoukar  13 , Farhang Babamahmoodi  15 , Ali Reza Davoudi Badabi  15 , Lotfollah Davoodi  15 , Mehdi Hassaniazad  16 , Elham Barahimi  16 , Abdolali Tousi  17 , Anahita Sadeghi  18 , Hadiseh Hosamirudsari  19 , Ali Ali Asgari  18 , Mohammad Abdollahi  18 , Amir Anushiravani  18 , Minoosh Shabani  20 , Shervin Shokouhi  20 , Nasim Khajavirad  21 , Mohammadreza Salehi  19 , Seyed Ali Dehghan Manshadi  19 , Hashem Mousavi  18 , Farnaz Zolfaghari  22 , Elmira Azimi  18 , Aida Zeinali  23 , Elham Akbarpour  18 , Dorsa Merat  18 , Gholamali Eslami  1 , Sajedeh Mousaviasl  1 , Sara Sayar  1 , Esmat Radmanesh  1 , Mona Ebrahimzadeh  1 , Zahra Arizavi  1 , Saeed Jelvay  1 , Shokrollah Salmanzadeh  1 , Hani Esmaeilian  1 , Morteza Mobarak  1 , Jalal Karimi  24 , Zahra Poormontaseri  24 , Nasrollah Hasooni Bahrini  2 , Atefeh Bonyadi  2 , Fatemeh Dehghani  2 , Hadi Mirzaei  25 , Masoome Noori Jangi  26 , Hossein Pourmasoomi  26 , Lili Rezaie Keikhaie  26 , Mahdi Afshari  27 , Alireza Nateghi Baygi  28 , Helia Nateghi Baygi  28 , Jacob Levi  29 , Kaitlyn McCann  30 , Hannah Wentzel  30 , Bryony Simmons  31 , Andrew Hill  32 , Shahin Merat  18
Affiliations
Randomized Controlled Trial

Evaluation of the effect of sofosbuvir and daclatasvir in hospitalized COVID-19 patients: a randomized double-blind clinical trial (DISCOVER)

Sara Mobarak et al. J Antimicrob Chemother. .

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 <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.

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Figures

Figure 1.
Figure 1.
Participant flow diagram. This figure appears in colour in the online version of JAC and in black and white in the print version of JAC.
Figure 2.
Figure 2.
Kaplan–Meier graph of the 28 day probability of hospital discharge. SOF/DCV, sofosbuvir/daclatasvir. This figure appears in colour in the online version of JAC and in black and white in the print version of JAC.
Figure 3.
Figure 3.
Kaplan–Meier graph of the 28 day probability of in-hospital mortality. SOF/DCV, sofosbuvir/daclatasvir. This figure appears in colour in the online version of JAC and in black and white in the print version of JAC.
See this image and copyright information in PMC

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