Abstract | BACKGROUND: METHODS: We randomly assigned 380 patients with Child-Pugh class A cirrhosis to receive either 12 or 24 weeks of treatment with ABT-450/r- ombitasvir (at a once-daily dose of 150 mg of ABT-450, 100 mg of ritonavir, and 25 mg of ombitasvir), dasabuvir (250 mg twice daily), and ribavirin administered according to body weight. The primary efficacy end point was a sustained virologic response 12 weeks after the end of treatment. The rate of sustained virologic response in each group was compared with the estimated rate with a telaprevir-based regimen (47%; 95% confidence interval [CI], 41 to 54). A noninferiority margin of 10.5 percentage points established 43% as the noninferiority threshold; the superiority threshold was 54%. RESULTS: A total of 191 of 208 patients who received 12 weeks of treatment had a sustained virologic response at post-treatment week 12, for a rate of 91.8% (97.5% CI, 87.6 to 96.1). A total of 165 of 172 patients who received 24 weeks of treatment had a sustained virologic response at post-treatment week 12, for a rate of 95.9% (97.5% CI, 92.6 to 99.3). These rates were superior to the historical control rate. The three most common adverse events were fatigue (in 32.7% of patients in the 12-week group and 46.5% of patients in the 24-week group), headache (in 27.9% and 30.8%, respectively), and nausea (in 17.8% and 20.3%, respectively). The hemoglobin level was less than 10 g per deciliter in 7.2% and 11.0% of patients in the respective groups. Overall, 2.1% of patients discontinued treatment owing to adverse events. CONCLUSIONS: In this phase 3 trial of an oral, interferon-free regimen evaluated exclusively in patients with HCV genotype 1 infection and cirrhosis, multitargeted therapy with the use of three new antiviral agents and ribavirin resulted in high rates of sustained virologic response. Drug discontinuations due to adverse events were infrequent. (Funded by AbbVie; TURQUOISE-II ClinicalTrials.gov number, NCT01704755.).
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Authors | Fred Poordad, Christophe Hezode, Roger Trinh, Kris V Kowdley, Stefan Zeuzem, Kosh Agarwal, Mitchell L Shiffman, Heiner Wedemeyer, Thomas Berg, Eric M Yoshida, Xavier Forns, Sandra S Lovell, Barbara Da Silva-Tillmann, Christine A Collins, Andrew L Campbell, Thomas Podsadecki, Barry Bernstein |
Journal | The New England journal of medicine
(N Engl J Med)
Vol. 370
Issue 21
Pg. 1973-82
(May 22 2014)
ISSN: 1533-4406 [Electronic] United States |
PMID | 24725237
(Publication Type: Clinical Trial, Phase III, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
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Chemical References |
- Anilides
- Antiviral Agents
- Carbamates
- Cyclopropanes
- Lactams, Macrocyclic
- Macrocyclic Compounds
- Sulfonamides
- ombitasvir
- Ribavirin
- Proline
- Valine
- paritaprevir
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Topics |
- Adult
- Aged
- Anilides
(adverse effects, therapeutic use)
- Antiviral Agents
(adverse effects, therapeutic use)
- Carbamates
(adverse effects, therapeutic use)
- Cyclopropanes
- Drug Resistance, Viral
- Drug Therapy, Combination
- Female
- Genotype
- Hepacivirus
(genetics, isolation & purification)
- Hepatitis C, Chronic
(complications, drug therapy)
- Humans
- Lactams, Macrocyclic
- Liver Cirrhosis
(drug therapy, etiology)
- Logistic Models
- Macrocyclic Compounds
(adverse effects, therapeutic use)
- Male
- Middle Aged
- Proline
(analogs & derivatives)
- Recurrence
- Ribavirin
(adverse effects, therapeutic use)
- Sulfonamides
- Valine
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