Abstract | BACKGROUND & AIMS: METHODS: Treatment-experienced patients (88% white and 35% prior null responders) with HCV genotype 1 infection and compensated cirrhosis were assigned randomly to groups given vaniprevir (600 mg twice daily) with peginterferon and ribavirin for 24 weeks (n = 16), vaniprevir (600 mg twice daily) for 24 weeks with peginterferon and ribavirin for 48 weeks (n = 14), vaniprevir (300 mg twice daily) with peginterferon and ribavirin for 48 weeks (n = 15), vaniprevir (600 mg twice daily) with peginterferon and ribavirin for 48 weeks (n = 15), or placebo with peginterferon and ribavirin for 48 weeks (n = 14, control). Cirrhosis was documented by liver biopsy (84%) or noninvasive methods (16%). Before randomization, participants were stratified based on their historical response to peginterferon and ribavirin. RESULTS: In the primary analysis, SVR rates among patients in the respective vaniprevir groups were 9 of 15 (60.0%), 9 of 13 (69.2%), 8 of 15 (53.3%), and 10 of 13 (76.9%), compared with 2 of 14 (14.3%) in the control group (pairwise P values ≤ .016). Cirrhotic patients with null or partial responses to prior therapy achieved SVR less often than patients with prior breakthrough or relapse, although 42.1% of prior null responders in the vaniprevir groups achieved SVRs. Patients in the vaniprevir groups more frequently experienced mild-moderate nausea, vomiting, and diarrhea than controls; 5% developed grade 2 anemia compared with none in the control group (no patient developed grade 3 or 4 anemia). Among patients in the vaniprevir groups who experienced virologic failure, resistance-associated variants were detected predominantly at positions 155, 156, and 168 in the HCV protease gene. CONCLUSIONS: In a controlled phase 2B trial, vaniprevir with peginterferon and ribavirin significantly increased rates of SVR among treatment-experienced patients with chronic HCV genotype 1 infection, compared with re-treatment with peginterferon and ribavirin alone. Vaniprevir generally was well tolerated for up to 48 weeks in patients with compensated cirrhosis. ClinicalTrials.gov number, NCT00704405.
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Authors | Maribel Rodriguez-Torres, Albrecht Stoehr, Edward J Gane, Lawrence Serfaty, Eric Lawitz, Amy Zhou, Michael Bourque, Sanhita Bhanja, Julie Strizki, Richard J O Barnard, Peggy M T Hwang, Mark J DiNubile, Niloufar Mobashery |
Journal | Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association
(Clin Gastroenterol Hepatol)
Vol. 12
Issue 6
Pg. 1029-37.e5
(Jun 2014)
ISSN: 1542-7714 [Electronic] United States |
PMID | 24120953
(Publication Type: Clinical Trial, Phase II, Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
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Copyright | Copyright © 2014 AGA Institute. Published by Elsevier Inc. All rights reserved. |
Chemical References |
- Antiviral Agents
- Cyclopropanes
- Indoles
- Interferon-alpha
- Isoindoles
- Lactams, Macrocyclic
- Placebos
- Sulfonamides
- Ribavirin
- Proline
- vaniprevir
- Leucine
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Topics |
- Adolescent
- Adult
- Aged
- Antiviral Agents
(therapeutic use)
- Cyclopropanes
- Double-Blind Method
- Drug Therapy, Combination
(methods)
- Female
- Genotype
- Hepacivirus
(classification, genetics, isolation & purification)
- Hepatitis C, Chronic
(complications, drug therapy, virology)
- Humans
- Indoles
(therapeutic use)
- Interferon-alpha
(therapeutic use)
- Isoindoles
- Lactams, Macrocyclic
- Leucine
(analogs & derivatives)
- Liver Cirrhosis
- Male
- Middle Aged
- Placebos
(administration & dosage)
- Proline
(analogs & derivatives)
- Ribavirin
(therapeutic use)
- Sulfonamides
- Treatment Outcome
- Viral Load
- Young Adult
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