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Evaluation of the Effect of Sofosbuvir and Daclatasvir in Hospitalized Covid-19 Patients: A Randomized Double-Blind Clinical Trial (Discover) Publisher Pubmed



Mobarak S1 ; Salasi M2 ; Hormati A3, 4 ; Khodadadi J5 ; Ziaee M6 ; Abedi F6 ; Ebrahimzadeh A6 ; Azarkar Z6 ; Mansourghanaei F7 ; Joukar F7 ; Yeganeh S8 ; Yaghubi Kalurazi T9 ; Naghipour M7 ; Mehrabi Z10 Show All Authors
Authors
  1. Mobarak S1
  2. Salasi M2
  3. Hormati A3, 4
  4. Khodadadi J5
  5. Ziaee M6
  6. Abedi F6
  7. Ebrahimzadeh A6
  8. Azarkar Z6
  9. Mansourghanaei F7
  10. Joukar F7
  11. Yeganeh S8
  12. Yaghubi Kalurazi T9
  13. Naghipour M7
  14. Mehrabi Z10
  15. Bahadori AR11
  16. Yaghoubi S10
  17. Moslemi R12
  18. Abbaspour Kasgari H13
  19. Fakheri H14
  20. Moghimi M13
  21. Shabani AM13
  22. Nekoukar Z13
  23. Babamahmoodi F15
  24. Davoudi Badabi AR15
  25. Davoodi L15
  26. Hassaniazad M16
  27. Barahimi E16
  28. Tousi A17
  29. Sadeghi A18
  30. Hosamirudsari H19
  31. Ali Asgari A18
  32. Abdollahi M18
  33. Anushiravani A18
  34. Shabani M20
  35. Shokouhi S20
  36. Khajavirad N21
  37. Salehi M19
  38. Dehghan Manshadi SA19
  39. Mousavi H18
  40. Zolfaghari F22
  41. Azimi E18
  42. Zeinali A23
  43. Akbarpour E18
  44. Merat D18
  45. Eslami G1
  46. Mousaviasl S1
  47. Sayar S1
  48. Radmanesh E1
  49. Ebrahimzadeh M1
  50. Arizavi Z1
  51. Jelvay S1
  52. Salmanzadeh S1
  53. Esmaeilian H1
  54. Mobarak M1
  55. Karimi J24
  56. Poormontaseri Z24
  57. Hasooni Bahrini N2
  58. Bonyadi A2
  59. Dehghani F2
  60. Mirzaei H25
  61. Noori Jangi M26
  62. Pourmasoomi H26
  63. Rezaie Keikhaie L26
  64. Afshari M27
  65. Nateghi Baygi A28
  66. Nateghi Baygi H28
  67. Levi J29
  68. Mccann K30
  69. Wentzel H30
  70. Simmons B31
  71. Hill A32
  72. Merat S18
Show Affiliations
Authors Affiliations
  1. 1. Abadan University of Medical Sciences, Abadan, Iran
  2. 2. Imam Khomeini Hospital of Abadan Petroleum Health Organization, Abadan, Iran
  3. 3. Colorectal Research Center, Iran University of Medical Sciences, Tehran, Iran
  4. 4. Gastroenterology and Hepatology Disease Research Center, Qom University of Medical Sciences, Qom, Iran
  5. 5. Infectious Disease Department, Qom University of Medical Sciences, Qom, Iran
  6. 6. Infectious Diseases Research Center, Birjand University of Medical Sciences, Birjand, Iran
  7. 7. Gastrointestinal and Liver Diseases Research Center, Guilan University of Medical Sciences, Rasht, Iran
  8. 8. Caspian Digestive Diseases Research Center, Guilan University of Medical Sciences, Rasht, Iran
  9. 9. Department of Health, Nutrition and Infectious Diseases, Guilan University of Medical Sciences, Rasht, Iran
  10. 10. Department of Infectious Diseases, Shiraz University of Medical Sciences, Shiraz, Iran
  11. 11. Student Research Committee, Shiraz University of Medical Sciences, Shiraz, Iran
  12. 12. Department of Clinical Pharmacy, Shiraz University of Medical Sciences, Shiraz, Iran
  13. 13. Department of Clinical Pharmacy, Mazandaran University of Medical Sciences, Sari, Iran
  14. 14. Gut and Liver Research Center, Non-communicable Disease Institute, Mazandaran University of Medical Sciences, Sari, Iran
  15. 15. Antimicrobial Resistance Research Center, Communicable Diseases Institute, Mazandaran University of Medical Sciences, Sari, Iran
  16. 16. Infectious and Tropical Diseases Research Center, Hormozgan University of Medical Sciences, Bandar Abbas, Iran
  17. 17. Student Research Committee, Hormozgan University of Medical Sciences, Bandar Abbas, Iran
  18. 18. Digestive Diseases Research Institute, Tehran University of Medical Sciences, Tehran, Iran
  19. 19. Infectious Diseases Department, Tehran University of Medical Sciences, Tehran, Iran
  20. 20. Department of Infectious Diseases and Tropical Medicine, Loghman Hakim Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran
  21. 21. Department of Internal Medicine, Tehran University of Medical Sciences, Tehran, Iran
  22. 22. Student Research Committee, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
  23. 23. Department of Cardiology, Tehran University of Medical Sciences, Tehran, Iran
  24. 24. Department of Infectious Disease, Fasa University of Medical Sciences, Fasa, Iran
  25. 25. Department of Biotechnology, School of Medicine, Zabol University of Medical Sciences, Zabol, Iran
  26. 26. Department of Infectious Diseases, School of Medicine, Zabol University of Medical Sciences, Zabol, Iran
  27. 27. Pediatric Gastroenterology and Hepatology Research Center, Zabol University of Medical Sciences, Zabol, Iran
  28. 28. Research and Development Department, Fanavaran Rojan Mohaghegh Darou Co., Tehran, Iran
  29. 29. Department of Intensive Care, University College London Hospital, London, United Kingdom
  30. 30. School of Public Health, Imperial College London, London, United Kingdom
  31. 31. Department of Infectious Diseases, Imperial College London, London, United Kingdom
  32. 32. Department of Pharmacology and Therapeutics, University of Liverpool, Liverpool, United Kingdom

Source: Journal of Antimicrobial Chemotherapy Published:2022


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. © 2021 The Author(s) 2021. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved.