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Sd1000: High Sustained Viral Response Rate in 1361 Patients With Hepatitis C Genotypes 1, 2, 3, and 4 Using a Low-Cost, Fixed-Dose Combination Tablet of Generic Sofosbuvir and Daclatasvir: A Multicenter, Phase Iii Clinical Trial Publisher Pubmed



Merat S1 ; Sharifi AH1 ; Poustchi H1 ; Hajiani E2 ; Gharavi A1 ; Karimi J3 ; Mansourghanaei F4 ; Fattahi MR5 ; Ahmadi L5 ; Somi MH6 ; Kalantari H7 ; Ghadir MR8 ; Sheikhesmaeili F9 ; Baniasadi N10 Show All Authors
Authors
  1. Merat S1
  2. Sharifi AH1
  3. Poustchi H1
  4. Hajiani E2
  5. Gharavi A1
  6. Karimi J3
  7. Mansourghanaei F4
  8. Fattahi MR5
  9. Ahmadi L5
  10. Somi MH6
  11. Kalantari H7
  12. Ghadir MR8
  13. Sheikhesmaeili F9
  14. Baniasadi N10
  15. Sohrabi M11
  16. Moosavy S12
  17. Ziaee M13
  18. Zahedi MJ14
  19. Mokhtare M15
  20. Sali S16
  21. Sayad B17
  22. Afshar B18
  23. Bakhshipour A19
  24. Parsi A2
  25. Sharifian A20
  26. Amiriani T21
  27. Malekzadeh Z1
  28. Merat D1
  29. Ganji A22
  30. Rahmanisamani F23
  31. Jamali R1
  32. Sofian M24
  33. Ghezlou M25
  34. Sohrabpour AA1
  35. Goshayeshi L22
  36. Valizadehtoosi SM26
  37. Eslami L1
  38. Maleki I26
  39. Hormati A8
  40. Shayesteh AA2
  41. Shayesteh E2
  42. Norouzi A22
  43. Abna Z27
  44. Janbakhsh A28
  45. Fakheri H26
  46. Minakari M29
  47. Sardarian H30
  48. Ghajary AF31
  49. Fattahiabdizadeh M32
  50. Latifnia M33
  51. Roozbeh F34
  52. Agah S15
  53. Fakhriehasl S4
  54. Nateghibaygi A1
  55. Fattahi B1
  56. Nateghibaygi H1
  57. Hill A35
  58. Malekzadeh R1
Show Affiliations
Authors Affiliations
  1. 1. Liver and Pancreatobiliary Diseases Research Center, Digestive Diseases Research Institute, Tehran University of Medical Sciences
  2. 2. Alimentary Tract Research Center, School of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
  3. 3. Department of Infectious Diseases and Tropical Medicine, Fasa University of Medical Sciences
  4. 4. Gastrointestinal and Liver Diseases Research Center, Guilan University of Medical Sciences, Rasht, Iran
  5. 5. Gastroenterohepatology Research Center, Shiraz University of Medical Sciences
  6. 6. Tabriz University of Medical Sciences
  7. 7. Isfahan Liver Disease Research Center, Isfahan University of Medical Sciences
  8. 8. Gastroenterology and Hepatology Disease Research Center, Qom University of Medical Sciences
  9. 9. Liver and Digestive Research Center, Kurdistan University of Medical Sciences, Sanandaj, Iran
  10. 10. Bam University of Medical Sciences
  11. 11. Gastrointestinal and Liver Diseases Research Center, Iran University of Medical Sciences, Tehran, Iran
  12. 12. Hormozgan University of Medical Science, Bandarabbas, Iran
  13. 13. Infectious Diseases Research Center, Birjand University of Medical Sciences
  14. 14. Gastroenterology and Hepatology Research Center, Kerman University of Medical Sciences
  15. 15. Colorectal Research Center, Iran University of Medical Science
  16. 16. Infectious Diseases and Tropical Medicine Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran
  17. 17. Infectious Diseases Research Center, Kermanshah University of Medical Sciences
  18. 18. Hamadan University of Medical Sciences
  19. 19. Infectious Diseases and Tropical Medicine Research Center, Zahedan University of Medical Sciences
  20. 20. Basic and Molecular Epidemiology of Gastrointestinal Disorders Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
  21. 21. Golestan Research Center for Gastroenterology and Hepatology, Golestan University of Medical Science, Gorgan, Romania
  22. 22. Department of Gastroenterology and Hepatology, Mashhad University of Medical Sciences
  23. 23. Shahrekord University of Medical Sciences
  24. 24. Infectious Disease Research Center, Arak University of Medical Science
  25. 25. Gastroenterology and Hepatology Disease Research Center, Arak Medical Sience University
  26. 26. Gut and Liver Research Center, Mazandaran University Of Medical Sciences, Sari, Iran
  27. 27. Sirjan University of Medical Sciences
  28. 28. Infectious Diseases Department, Kermanshah University of Medical Sciences
  29. 29. Isfahan University of Medical Sciences
  30. 30. Guilan University of Medical Science, Bandar Anzali, Iran
  31. 31. Chamran Hospital of Saveh
  32. 32. Department of Microbiology
  33. 33. Department of Gastroenterology and Hepatology, Sabzevar University of Medical Sciences
  34. 34. Mazandaran University of Medical Sciences, Sari, Iran
  35. 35. Department of Translational Medicine, University of Liverpool, United Kingdom

Source: Clinical Infectious Diseases Published:2020


Abstract

Background. The combination of sofosbuvir and daclatasvir is a potent, pangenotypic regimen suitable for mass-scale hepatitis C treatment, especially in resource-limited countries where newer, expensive combinations are not available. This combination has been widely tested on genotype 4. However, Phase III trials of this combination in other genotypes have been cost prohibitive. With the introduction of generic, low-cost sofosbuvir and daclatasvir, large-scale studies in resource-limited countries are now possible. Methods. Sofosbuvir at 400 mg and daclatasvir at 60 mg were coformulated into a fixed-dose combination (FDC) tablet (Sovodak, Rojan Pharma, Tehran, Iran). Patients from 46 centers were dosed for 12 or 24 weeks with or without ribavirin, in line with existing guidelines. Responses to treatment were evaluated 12 weeks after the end of treatment (for a sustained virological response at Week 12; SVR12). Results. There were 1361 patients recruited. Overall, the patients were 21% female, with a mean age of 50 years; 39% were cirrhotic; 22% were treatment-experienced; 47% were genotype 1, 41% were genotype 3, and 2% were other genotypes. The genotype was not known in 10% of the patients. The intention-to-treat and per-protocol SVR12 rates were 94.7% and 98.8%, respectively. The safety profile was unremarkable, treatment was well tolerated, and compliance with the single-tablet regimen was excellent. Conclusions. The treatment with FDC of sofosbuvir and daclatasvir achieved high SVR12 rates, equivalent to those seen in Phase III trials of other pangenotypic options, and has been conducted at a similar scale in a representative, real-world population at a cost of under $100 per patient, which makes this combination suitable for elimination protocols in resource-limited countries. © The Author(s) 2019. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved.
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