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A Pragmatic, Randomized Controlled Trial of Oral Antivirals for the Treatment of Chronic Hepatitis C: The PRIORITIZE Study.

Publication ,  Journal Article
Sulkowski, MS; Moon, JS; Sherman, KE; Morelli, G; Darling, JM; Muir, AJ; Khalili, M; Fishbein, DA; Hinestrosa, F; Shiffman, ML; Di Bisceglie, A ...
Published in: Hepatology
December 2021

BACKGROUND AND AIMS: Multiple direct-acting antiviral (DAA) regimens are available to treat HCV genotype 1 infection. However, comparative effectiveness from randomized controlled trials of DAA regimens is unavailable. APPROACH AND RESULTS: We conducted a pragmatic randomized controlled trial (NCT02786537) to compare the effectiveness of DAAs for HCV genotype 1a or 1b on viral response, safety, tolerability, and medication nonadherence. Adults with compensated liver disease, HCV genotype 1, not pregnant or breastfeeding, and with health insurance likely to cover ledipasvir/sofosbuvir (LDV/SOF) were recruited from 34 US viral hepatitis clinics. Participants were randomized (± ribavirin) to LDV/SOF, elbasvir/grazoprevir (EBR/GZR), and paritaprevir/ritonavir/ombitasvir+dasabuvir (PrOD; treatment arm stopped early). Primary outcomes included sustained viral response at 12 weeks (SVR12), clinician-recorded adverse events, patient-reported symptoms, and medication nonadherence. Between June 2016 and March 2018, 1,609 participants were randomized. Among 1,128 participants who received ≥1 dose of EBR/GZR or LDV/SOF (± ribavirin), SVR12 was 95.2% (95% CI, 92.8%-97.6%) and 97.4% (95% CI, 95.5%-99.2%), respectively, with a difference estimate of 2.2% (-0.5% to 4.7%), falling within the "equivalence" interval (-5% to 5%). While most (56%) participants experienced adverse events, few were serious (4.2%) or severe (1.8%). In the absence of ribavirin, discontinuations due to adverse events were rare. Patient-reported symptoms and medication nonadherence were similar. Study limitations were dropout due to insurance denial and loss to follow-up after treatment, limiting the ability to measure SVR12. CONCLUSIONS: This pragmatic trial demonstrated high SVR12 for participants treated with EBR/GZR and LDV/SOF with few adverse effects. Overall, the two regimens were equivalent in effectiveness. The results support current HCV guidelines that do not distinguish between ribavirin-free EBR/GZR and LDV/SOF.

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Published In

Hepatology

DOI

EISSN

1527-3350

Publication Date

December 2021

Volume

74

Issue

6

Start / End Page

2952 / 2964

Location

United States

Related Subject Headings

  • Young Adult
  • Valine
  • Uracil
  • Treatment Outcome
  • Sustained Virologic Response
  • Sulfonamides
  • Sofosbuvir
  • Ribavirin
  • RNA, Viral
  • Quinoxalines
 

Citation

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Sulkowski, M. S., Moon, J. S., Sherman, K. E., Morelli, G., Darling, J. M., Muir, A. J., … PRIORITIZE Study Team, . (2021). A Pragmatic, Randomized Controlled Trial of Oral Antivirals for the Treatment of Chronic Hepatitis C: The PRIORITIZE Study. Hepatology, 74(6), 2952–2964. https://doi.org/10.1002/hep.32053
Sulkowski, Mark S., Juhi S. Moon, Kenneth E. Sherman, Giuseppe Morelli, Jama M. Darling, Andrew J. Muir, Mandana Khalili, et al. “A Pragmatic, Randomized Controlled Trial of Oral Antivirals for the Treatment of Chronic Hepatitis C: The PRIORITIZE Study.Hepatology 74, no. 6 (December 2021): 2952–64. https://doi.org/10.1002/hep.32053.
Sulkowski MS, Moon JS, Sherman KE, Morelli G, Darling JM, Muir AJ, et al. A Pragmatic, Randomized Controlled Trial of Oral Antivirals for the Treatment of Chronic Hepatitis C: The PRIORITIZE Study. Hepatology. 2021 Dec;74(6):2952–64.
Sulkowski, Mark S., et al. “A Pragmatic, Randomized Controlled Trial of Oral Antivirals for the Treatment of Chronic Hepatitis C: The PRIORITIZE Study.Hepatology, vol. 74, no. 6, Dec. 2021, pp. 2952–64. Pubmed, doi:10.1002/hep.32053.
Sulkowski MS, Moon JS, Sherman KE, Morelli G, Darling JM, Muir AJ, Khalili M, Fishbein DA, Hinestrosa F, Shiffman ML, Di Bisceglie A, Rajender Reddy K, Pearlman B, Lok AS, Fried MW, Stewart PW, Peter J, Wadsworth S, Kixmiller S, Sloan A, Vainorius M, Horne PM, Michael L, Dong M, Evon DM, Segal JB, Nelson DR, PRIORITIZE Study Team. A Pragmatic, Randomized Controlled Trial of Oral Antivirals for the Treatment of Chronic Hepatitis C: The PRIORITIZE Study. Hepatology. 2021 Dec;74(6):2952–2964.
Journal cover image

Published In

Hepatology

DOI

EISSN

1527-3350

Publication Date

December 2021

Volume

74

Issue

6

Start / End Page

2952 / 2964

Location

United States

Related Subject Headings

  • Young Adult
  • Valine
  • Uracil
  • Treatment Outcome
  • Sustained Virologic Response
  • Sulfonamides
  • Sofosbuvir
  • Ribavirin
  • RNA, Viral
  • Quinoxalines