A Pragmatic, Randomized Controlled Trial of Oral Antivirals for the Treatment of Chronic Hepatitis C: The PRIORITIZE Study.
A Pragmatic, Randomized Controlled Trial of Oral Antivirals for the Treatment of Chronic Hepatitis C: The PRIORITIZE Study.
- 2021
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. 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. 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. Copyright (c) 2021 The Authors. Hepatology published by Wiley Periodicals LLC on behalf of American Association for the Study of Liver Diseases.
English
0270-9139
10.1002/hep.32053 [doi] NIHMS1752507 [mid] PMC8639765 [pmc]
*Antiviral Agents/ad [Administration & Dosage]
*Hepacivirus/ip [Isolation & Purification]
*Hepatitis C, Chronic/dt [Drug Therapy]
2-Naphthylamine/ad [Administration & Dosage]
Administration, Oral
Adolescent
Adult
Aged
Aged, 80 and over
Anilides/ad [Administration & Dosage]
Benzimidazoles/ad [Administration & Dosage]
Benzofurans/ad [Administration & Dosage]
Cyclopropanes/ad [Administration & Dosage]
Drug Combinations
Drug Therapy, Combination/mt [Methods]
Female
Fluorenes/ad [Administration & Dosage]
Follow-Up Studies
Genotyping Techniques
Hepacivirus/ge [Genetics]
Hepatitis C, Chronic/bl [Blood]
Hepatitis C, Chronic/di [Diagnosis]
Hepatitis C, Chronic/vi [Virology]
Humans
Imidazoles/ad [Administration & Dosage]
Lactams, Macrocyclic/ad [Administration & Dosage]
Male
Middle Aged
Proline/aa [Analogs & Derivatives]
Proline/ad [Administration & Dosage]
Quinoxalines/ad [Administration & Dosage]
Ribavirin/ad [Administration & Dosage]
RNA, Viral/bl [Blood]
Sofosbuvir/ad [Administration & Dosage]
Sulfonamides/ad [Administration & Dosage]
Sustained Virologic Response
Treatment Outcome
Uracil/aa [Analogs & Derivatives]
Uracil/ad [Administration & Dosage]
Valine/ad [Administration & Dosage]
Young Adult
MedStar Health Research Institute
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
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. 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. 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. Copyright (c) 2021 The Authors. Hepatology published by Wiley Periodicals LLC on behalf of American Association for the Study of Liver Diseases.
English
0270-9139
10.1002/hep.32053 [doi] NIHMS1752507 [mid] PMC8639765 [pmc]
*Antiviral Agents/ad [Administration & Dosage]
*Hepacivirus/ip [Isolation & Purification]
*Hepatitis C, Chronic/dt [Drug Therapy]
2-Naphthylamine/ad [Administration & Dosage]
Administration, Oral
Adolescent
Adult
Aged
Aged, 80 and over
Anilides/ad [Administration & Dosage]
Benzimidazoles/ad [Administration & Dosage]
Benzofurans/ad [Administration & Dosage]
Cyclopropanes/ad [Administration & Dosage]
Drug Combinations
Drug Therapy, Combination/mt [Methods]
Female
Fluorenes/ad [Administration & Dosage]
Follow-Up Studies
Genotyping Techniques
Hepacivirus/ge [Genetics]
Hepatitis C, Chronic/bl [Blood]
Hepatitis C, Chronic/di [Diagnosis]
Hepatitis C, Chronic/vi [Virology]
Humans
Imidazoles/ad [Administration & Dosage]
Lactams, Macrocyclic/ad [Administration & Dosage]
Male
Middle Aged
Proline/aa [Analogs & Derivatives]
Proline/ad [Administration & Dosage]
Quinoxalines/ad [Administration & Dosage]
Ribavirin/ad [Administration & Dosage]
RNA, Viral/bl [Blood]
Sofosbuvir/ad [Administration & Dosage]
Sulfonamides/ad [Administration & Dosage]
Sustained Virologic Response
Treatment Outcome
Uracil/aa [Analogs & Derivatives]
Uracil/ad [Administration & Dosage]
Valine/ad [Administration & Dosage]
Young Adult
MedStar Health Research Institute
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't