Efficacy and safety of sofosbuvir in the treatment of SARS-CoV-2: an open label phase II trial
-
Mostafa Alavi-Moghaddam
,
Mohammad Sistanizad
,
Mehrdad Haghighi
,
Tahereh Sabaghian
,
Bahare Gholami Chaboki
,
Zahra Soroureddin
Abstract
Objective: Despite the worldwide spread of the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), an effective specific antiviral treatment for coronavirus disease of 2019 (COVID-19) is yet to be identified .We did this study to investigate the safety and efficacy of sofosbuvir as antiviral therapy among hospitalized adult patients with SARS-CoV-2. Methods: Patients were randomized into intervention arm receiving sofosbuvir or comparison arm receiving usual antiviral agents in addition to standard of care. The primary end point of the study was clinical recovery as defined by normal body temperature and normal oxygen saturation. The main secondary outcome was all-cause mortality during the admission in hospital or within 14 days after discharge if applicable. Reports of severe adverse events were observed in the intervention arm. Results: Fifty-seven patients enrolled into either the clinical trial arm (n=27) or the comparison arm (n=30). Primary outcome was achieved by 24 (88.9%) and 10 (33.3%) in the intervention and comparison arms, respectively. Median hospital length of stay was significantly shorter in the intervention arm (10 days [IQR: 5-12] vs. 11.5 days [IQR: 8.5-17.75], P = 0.016). All-cause mortality was two and thirteen in intervention and comparison groups, respectively. No serious adverse events were reported by the patients receiving sofosbuvir during the study. Conclusion: Among patients hospitalized with SARS-CoV-2, those who received sofosbuvir had more clinical recovery rate and had a shorter hospital length of stay than those who received usual antiviral agents in the study and these differences were statistically significant.
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8. Jacobson IM, Gordon SC, Kowdley KV, Yoshida EM, Rodriguez-Torres M, Sulkowski MS, et al. Sofosbuvir for hepatitis C genotype 2 or 3 in patients without treatment options. N Engl J Med. 2013;368(20):1867-77.
9. Naggie S, Sulkowski M, Lalezari J, Fessel J, Mounzer K, Shuhart M, et al. All-oral therapy with sofosbuvir plus ribavirin for the treatment of HCV genotype 1, 2, and 3 infection in patients co-infected with HIV (PHOTON-1). 21st conference on retroviruses and opportunistic infections (CROI). Boston, MA; March 3-6, 2014.
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11. Smolders EJ, de Kanter CT, van Hoek B, Arends JE, Drenth JP, Burger DM. Pharmacokinetics, efficacy, and safety of hepatitis C virus drugs in patients with liver and/or renal impairment. Drug saf. 2016;39(7):589-611.
12. Bullard-Feibelman KM, Govero J, Zhu Z, Salazar V, Veselinovic M, Diamond MS, et al. The FDA-approved drug sofosbuvir inhibits Zika virus infection. Antiviral Res. 2017;137:134-40.
13. Sacramento CQ, de Melo GR, de Freitas CS, Rocha N, Hoelz LV, Miranda M, et al. The clinically approved antiviral drug sofosbuvir inhibits Zika virus replication. Sci Rep. 2017;7:40920.
14. Onorati M, Li Z, Liu F, Sousa AMM, Nakagawa N, Li M, et al. Zika virus disrupts phospho-TBK1 localization and mitosis in human neuroepithelial stem cells and radial glia. Cell Rep. 2016;16(10):2576-92.
15. Ferreira AC, Reis PA, de Freitas CS, Sacramento CQ, Villas Bôas Hoelz L, Bastos MM, et al. Beyond members of the flaviviridae family, sofosbuvir also inhibits chikungunya virus replication. Antimicrob Agents Chemother. 2019;63(2):e01389-18.
16. Elfiky AA. Anti-HCV, nucleotide inhibitors, repurposing against COVID-19. Life Sci. 2020;248:117477.
17. Kumar P, Kulkarni A, Sharma M, Rao PN. Repurposing hepatitis C direct-acting antivirals against COVID-19. J Clin Expe Hepatol. 2021;11(2):273-5.
18. Sayad B, Sobhani M, Khodarahmi R. Sofosbuvir as repurposed antiviral drug against COVID-19: why were we convinced to evaluate the drug in a registered/approved clinical trial? Arc Med Res. 2020;51(6):577-81.
19. Vijayananthan A, Nawawi O. The importance of Good Clinical Practice guidelines and its role in clinical trials. Biomed Imaging Interv J. 2008;4(1):e5.
20. Sadeghi A, Ali Asgari A, Norouzi A, Kheiri Z, Anushirvani A, Montazeri M, et al. Sofosbuvir and daclatasvir compared with standard of care in the treatment of patients admitted to hospital with moderate or severe coronavirus infection (COVID-19): a randomized controlled trial. J Antimicrob Chemother. 2020;75(11):3379-85.
21. Eslami G, Mousaviasl S, Radmanesh E, Jelvay S, Bitaraf S, Simmons B, et al. The impact of sofosbuvir/daclatasvir or ribavirin in patients with severe COVID-19. JAntimicrob Chemother. 2020;75(11):3366-72.
22. Abbaspour Kasgari H, Moradi S, Shabani AM, Babamahmoodi F, Davoudi Badabi AR, Davoudi L, et al. Evaluation of the efficacy of sofosbuvir plus daclatasvir in combination with ribavirin for hospitalized COVID-19 patients with moderate disease compared with standard care: a single-centre, randomized controlled trial. J Antimicrob Chemother. 2020;75(11):3373-8.
23. Khalili H, Nourian A, Ahmadinejad Z, Emadi Kouchak H, Jafari S, Dehghan Manshadi SA, et al. Efficacy and safety of sofosbuvir/ ledipasvir in treatment of patients with COVID-19: a randomized clinical trial. Acta biomed. 2020;91(4):e2020102.
24. Sayad B, Khodarahmi R, Najafi F, Miladi R, Mohseni Afshar Z, Mansouri F, et al. Efficacy and safety of sofosbuvir/velpatasvir versus the standard of care in adults hospitalized with COVID-19: a single-centre, randomized controlled trial. J Antimicrob Chemother. 2021;76(8):2158-67.
25. Simmons B, Wentzel H, Mobarak S, Eslami G, Sadeghi A, Ali Asgari A, et al. Sofosbuvir/daclatasvir regimens for the treatment of COVID-19: an individual patient data meta-analysis. J Antimicrob Chemother. 2021;72(2):286-91.
26. Vetter P, Eckerle I, Kaiser L. Covid-19: a puzzle with many missing pieces. BMJ. 2020;368:m627.
27. Solidarity clinical trial for COVID-19 treatments: World Health Organization; 2019. Available from: https://www.who.int/emergencies/diseases/novel-coronavirus-2019/global-research-on-novel-coronavirus-2019-ncov/solidarity-clinical-trial-for-covid-19-treatments.
28. Recovery Collaborative Group; Horby P, Mafham M, Linsell L, Bell JL, Staplin N, Emberson JR, et al. Effect of hydroxychloroquine in hospitalized patients with Covid-19. N Engl J Med. 2020;383(21):2030-40.
29. Cao B, Wang Y, Wen D, Liu W, Wang J, Fan G, et al. A trial of lopinavir-ritonavir in adults hospitalized with severe Covid-19. N Engl J Med. 2020;382(19):1787-99.
30. WHO discontinues hydroxychloroquine and lopinavir/ritonavir treatment arms for COVID-19: World Health Organization; 2020. Available from: https://www.who.int/news/item/04-07-2020-who-discontinues-hydroxychloroquine-and-lopinavir-ritonavir-treatment-arms-for-covid-19.
31. Rahmani H, Davoudi-Monfared E, Nourian A, Khalili H, Hajizadeh N, Jalalabadi NZ, et al. Interferon β-1b in treatment of severe COVID-19: a randomized clinical trial. Int Immunopharmacol. 2020;88:106903.
32. Hung IF, Lung KC, Tso EY, Liu R, Chung TW, Chu MY, et al. Triple combination of interferon beta-1b, lopinavir–ritonavir, and ribavirin in the treatment of patients admitted to hospital with COVID-19: an open-label, randomised, phase 2 trial. Lancet. 2020;395(10238):1695-1704.
33. Tong S, Su Y, Yu Y, Wu C, Chen J, Wang S, et al. Ribavirin therapy for severe COVID-19: a retrospective cohort study. Int J Antimicrob Agents. 2020;56(3):106114.
34. Beigel JH, Tomashek KM, Dodd LE, Mehta AK, Zingman BS, Kalil AC, et al. Remdesivir for the treatment of Covid-19 - final report. N Engl Jl Med. 2020;383(19):1813-26.
35. Goldman JD, Lye DCB, Hui DS, Marks KM, Bruno R, Montejano R, et al. Remdesivir for 5 or 10 days in patients with severe Covid-19. N Engl J Med. 2020;383(19):1827-37.
36. Spinner CD, Gottlieb RL, Criner GJ, Arribas López JR, Cattelan AM, Soriano Viladomiu A, et al. Effect of remdesivir vs standard care on clinical status at 11 days in patients with moderate COVID-19: a randomized clinical trial. JAMA. 2020;324(11):1048-57.
37. Recovery Collaborative Group; Horby P, Lim WS, Emberson JR, Mafham M, Bell JL, Linsell L, et al. Dexamethasone in hospitalized patients with Covid-19. N Engl J Med. 2021;384(8):693-704.
2. Rahimi F, Talebi Bezmin Abadi A. Practical strategies against the novel coronavirus and COVID-19-the imminent global threat. Arch Med Res. 2020;51(3):280-1.
3. Chien M, Anderson TK, Jockusch S, Tao C, Li X, Kumar S, et al. Nucleotide analogues as inhibitors of SARS-CoV-2 polymerase, a key drug target for COVID-19. J Proteome Res. 2020;19(11):4690-7.
4. Ju J, Li X, Kumar S, Jockusch S, Chien M, Tao C, et al. Nucleotide analogues as inhibitors of SARS-CoV polymerase. Pharmacol Res Perspect. 2020;8(6):e00674.
5. te Velthuis AJ. Common and unique features of viral RNA-dependent polymerases. Cell Mol Life Sci. 2014;71(22):4403-20.
6. Svarovskaia ES, Dvory-Sobol HS, Hebner C, Doehle B, Gontcharova V, Martin R, et al. No resistance detected in four phase 3 clinical studies in HCV genotype 1-6 of sofosbuvir+ ribavirin with or without peginterferon.64rd annual meeting of the American Association for the Study of Liver Disease. Washington, DC; Nov 1-5, 2013.
7. Lawitz E, Mangia A, Wyles D, Rodriguez-Torres M, Hassanein T, Gordon SC, et al. Sofosbuvir for previously untreated chronic hepatitis C infection. N Engl J Med. 2013;368(20):1878-87.
8. Jacobson IM, Gordon SC, Kowdley KV, Yoshida EM, Rodriguez-Torres M, Sulkowski MS, et al. Sofosbuvir for hepatitis C genotype 2 or 3 in patients without treatment options. N Engl J Med. 2013;368(20):1867-77.
9. Naggie S, Sulkowski M, Lalezari J, Fessel J, Mounzer K, Shuhart M, et al. All-oral therapy with sofosbuvir plus ribavirin for the treatment of HCV genotype 1, 2, and 3 infection in patients co-infected with HIV (PHOTON-1). 21st conference on retroviruses and opportunistic infections (CROI). Boston, MA; March 3-6, 2014.
10. Mariño Z, van Bömmel F, Forns X, Berg T. New concepts of sofosbuvir-based treatment regimens in patients with hepatitis C. Gut. 2014;63(2):207-15.
11. Smolders EJ, de Kanter CT, van Hoek B, Arends JE, Drenth JP, Burger DM. Pharmacokinetics, efficacy, and safety of hepatitis C virus drugs in patients with liver and/or renal impairment. Drug saf. 2016;39(7):589-611.
12. Bullard-Feibelman KM, Govero J, Zhu Z, Salazar V, Veselinovic M, Diamond MS, et al. The FDA-approved drug sofosbuvir inhibits Zika virus infection. Antiviral Res. 2017;137:134-40.
13. Sacramento CQ, de Melo GR, de Freitas CS, Rocha N, Hoelz LV, Miranda M, et al. The clinically approved antiviral drug sofosbuvir inhibits Zika virus replication. Sci Rep. 2017;7:40920.
14. Onorati M, Li Z, Liu F, Sousa AMM, Nakagawa N, Li M, et al. Zika virus disrupts phospho-TBK1 localization and mitosis in human neuroepithelial stem cells and radial glia. Cell Rep. 2016;16(10):2576-92.
15. Ferreira AC, Reis PA, de Freitas CS, Sacramento CQ, Villas Bôas Hoelz L, Bastos MM, et al. Beyond members of the flaviviridae family, sofosbuvir also inhibits chikungunya virus replication. Antimicrob Agents Chemother. 2019;63(2):e01389-18.
16. Elfiky AA. Anti-HCV, nucleotide inhibitors, repurposing against COVID-19. Life Sci. 2020;248:117477.
17. Kumar P, Kulkarni A, Sharma M, Rao PN. Repurposing hepatitis C direct-acting antivirals against COVID-19. J Clin Expe Hepatol. 2021;11(2):273-5.
18. Sayad B, Sobhani M, Khodarahmi R. Sofosbuvir as repurposed antiviral drug against COVID-19: why were we convinced to evaluate the drug in a registered/approved clinical trial? Arc Med Res. 2020;51(6):577-81.
19. Vijayananthan A, Nawawi O. The importance of Good Clinical Practice guidelines and its role in clinical trials. Biomed Imaging Interv J. 2008;4(1):e5.
20. Sadeghi A, Ali Asgari A, Norouzi A, Kheiri Z, Anushirvani A, Montazeri M, et al. Sofosbuvir and daclatasvir compared with standard of care in the treatment of patients admitted to hospital with moderate or severe coronavirus infection (COVID-19): a randomized controlled trial. J Antimicrob Chemother. 2020;75(11):3379-85.
21. Eslami G, Mousaviasl S, Radmanesh E, Jelvay S, Bitaraf S, Simmons B, et al. The impact of sofosbuvir/daclatasvir or ribavirin in patients with severe COVID-19. JAntimicrob Chemother. 2020;75(11):3366-72.
22. Abbaspour Kasgari H, Moradi S, Shabani AM, Babamahmoodi F, Davoudi Badabi AR, Davoudi L, et al. Evaluation of the efficacy of sofosbuvir plus daclatasvir in combination with ribavirin for hospitalized COVID-19 patients with moderate disease compared with standard care: a single-centre, randomized controlled trial. J Antimicrob Chemother. 2020;75(11):3373-8.
23. Khalili H, Nourian A, Ahmadinejad Z, Emadi Kouchak H, Jafari S, Dehghan Manshadi SA, et al. Efficacy and safety of sofosbuvir/ ledipasvir in treatment of patients with COVID-19: a randomized clinical trial. Acta biomed. 2020;91(4):e2020102.
24. Sayad B, Khodarahmi R, Najafi F, Miladi R, Mohseni Afshar Z, Mansouri F, et al. Efficacy and safety of sofosbuvir/velpatasvir versus the standard of care in adults hospitalized with COVID-19: a single-centre, randomized controlled trial. J Antimicrob Chemother. 2021;76(8):2158-67.
25. Simmons B, Wentzel H, Mobarak S, Eslami G, Sadeghi A, Ali Asgari A, et al. Sofosbuvir/daclatasvir regimens for the treatment of COVID-19: an individual patient data meta-analysis. J Antimicrob Chemother. 2021;72(2):286-91.
26. Vetter P, Eckerle I, Kaiser L. Covid-19: a puzzle with many missing pieces. BMJ. 2020;368:m627.
27. Solidarity clinical trial for COVID-19 treatments: World Health Organization; 2019. Available from: https://www.who.int/emergencies/diseases/novel-coronavirus-2019/global-research-on-novel-coronavirus-2019-ncov/solidarity-clinical-trial-for-covid-19-treatments.
28. Recovery Collaborative Group; Horby P, Mafham M, Linsell L, Bell JL, Staplin N, Emberson JR, et al. Effect of hydroxychloroquine in hospitalized patients with Covid-19. N Engl J Med. 2020;383(21):2030-40.
29. Cao B, Wang Y, Wen D, Liu W, Wang J, Fan G, et al. A trial of lopinavir-ritonavir in adults hospitalized with severe Covid-19. N Engl J Med. 2020;382(19):1787-99.
30. WHO discontinues hydroxychloroquine and lopinavir/ritonavir treatment arms for COVID-19: World Health Organization; 2020. Available from: https://www.who.int/news/item/04-07-2020-who-discontinues-hydroxychloroquine-and-lopinavir-ritonavir-treatment-arms-for-covid-19.
31. Rahmani H, Davoudi-Monfared E, Nourian A, Khalili H, Hajizadeh N, Jalalabadi NZ, et al. Interferon β-1b in treatment of severe COVID-19: a randomized clinical trial. Int Immunopharmacol. 2020;88:106903.
32. Hung IF, Lung KC, Tso EY, Liu R, Chung TW, Chu MY, et al. Triple combination of interferon beta-1b, lopinavir–ritonavir, and ribavirin in the treatment of patients admitted to hospital with COVID-19: an open-label, randomised, phase 2 trial. Lancet. 2020;395(10238):1695-1704.
33. Tong S, Su Y, Yu Y, Wu C, Chen J, Wang S, et al. Ribavirin therapy for severe COVID-19: a retrospective cohort study. Int J Antimicrob Agents. 2020;56(3):106114.
34. Beigel JH, Tomashek KM, Dodd LE, Mehta AK, Zingman BS, Kalil AC, et al. Remdesivir for the treatment of Covid-19 - final report. N Engl Jl Med. 2020;383(19):1813-26.
35. Goldman JD, Lye DCB, Hui DS, Marks KM, Bruno R, Montejano R, et al. Remdesivir for 5 or 10 days in patients with severe Covid-19. N Engl J Med. 2020;383(19):1827-37.
36. Spinner CD, Gottlieb RL, Criner GJ, Arribas López JR, Cattelan AM, Soriano Viladomiu A, et al. Effect of remdesivir vs standard care on clinical status at 11 days in patients with moderate COVID-19: a randomized clinical trial. JAMA. 2020;324(11):1048-57.
37. Recovery Collaborative Group; Horby P, Lim WS, Emberson JR, Mafham M, Bell JL, Linsell L, et al. Dexamethasone in hospitalized patients with Covid-19. N Engl J Med. 2021;384(8):693-704.
| Files | ||
| Issue | Vol 7 No 1 (2023): Winter (February) | |
| Section | Original article | |
| DOI | 10.18502/fem.v7i1.11697 | |
| Keywords | ||
| Antiviral Agents COVID-19 SARS-Cov-2 Sofosbuvir | ||
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How to Cite
1.
Alavi-Moghaddam M, Sistanizad M, Haghighi M, Sabaghian T, Gholami Chaboki B, Soroureddin Z. Efficacy and safety of sofosbuvir in the treatment of SARS-CoV-2: an open label phase II trial. Front Emerg Med. 2023;7(1):e7.
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