Kwo PY. NEJM 2014;371:2375-82CORAL-I
Design
OBV/PTV/r + DSV + RBV
Open labelPhase II
18-70 yearsChronic HCV infection, genotype 1
Liver transplantation for HCV≥ 12 months ago
HCV RNA > 10,000 IU/mlTreatment naïve or prior IFN-based
regimen prior to transplantationMetavir ≤ F2 by biopsy
No HBV or HIV coinfection
CORAL Study: OBV/PTV/r + DSV + RBV in liver transplantation with recurrent genotype 1 infection
W24
N = 34
Stable immunosuppressive therapy : tacrolimus or cyclosporin ; glucocorticoïds at dose ≤ 5 mg/day permitted Treatment regimens
– Co-formulated ombitasvir/paritaprevir/rironavir/ (OBV/PTV/r/): 25/150/100 mg qd = 2 tablets
– Dasabuvir (DSV) : 250 mg bid– RBV : dose selected by investigator (most often 600-800 mg/day)
Objective– SVR12, by intention to treat, with 95% CI, descriptive analysis
N = 34Demographics and clinical characteristics
Mean age, years 60
Female 31%
Genotype 1a 85%
IL28B CC genotype 24%
HCV RNA log10 IU/ml, mean (SD) 6.6 ± 0.5
Metavir F0 / F1 / F2, % 18% / 38% / 44%
Lack of response to previous IFN treatment 71%
Time since liver transplantation, months, median 39.5
Tacrolimus / ciclosporine, % 85% / 15%
Outcome, % (95% CI)HCV RNA < 25 IU/ml at W24 (end of treatment) 100% (90-100)
SVR12 (HCV RNA < 25 IU/ml) 97% (85-100)
Relapse, n, % 1* , 3%
Baseline characteristics and treatment response
* At relapse : resistance-associated variants R155K in NS3, M28T and Q30R in NS5A, and G554S in NS5B
Kwo PY. NEJM 2014;371:2375-82CORAL-I
CORAL Study: OBV/PTV/r + DSV + RBV in liver transplantation with recurrent genotype 1 infection
AE leading to discontinuation 1 (3%)*
Serious adverse events 2 (6%)
Fatigue 50%
Headache 44%
Cough 32%
Anemia 29%
Diarrhea 26%
Insomnia 26%
Asthenia 24%
Nausea 24%
Muscle spasms 21%
Back pain 18%
Dizziness 18%
Peripheral edema 18%
Rhinorrhea 18%
Adverse events and laboratory abnormalities in the 34 patients, N (%)
Grade 3 laboratory abnormalitiesALT 0
AST 0
Total bilirubin 2 (6%)
Hemoglobin 1 (3%)
Creatinine 0
* W18 : rash, memory impairment, and anxiety.SVR12 despite premature discontinuation
No graft rejection and no deaths
Kwo PY. NEJM 2014;371:2375-82CORAL-I
CORAL Study: OBV/PTV/r + DSV + RBV in liver transplantation with recurrent genotype 1 infection
CORAL Study: OBV/PTV/r + DSV + RBV in liver transplantation with recurrent genotype 1 infection
Summary– In this phase II trial of a 24-week, IFN-free, all-oral antiviral regimen for
HCV genotype 1 infection, a rate of sustained virologic response of 97% (95% CI, 85 to 100) at post-treatment weeks 12 and 24 was observed among liver-transplant recipients with no fibrosis or mild fibrosis.
– No deaths or episodes of graft rejection– Very good tolerability and safety– No patient needed a blood transfusion ; 5 patients (15%) required
erythropoietin, all of whom had initially received RBV at a total daily dose of 1000 or 1200 mg
• Given the high SVR12, regardless of the initial RBV dose, an initial dose of 600 to 800 mg may provide sufficient therapeutic benefit and minimize the risk of severe anemia
– Limitations• Patients with advanced fibrosis excluded• Patients with aggressive forms of recurrent HCV infection (e.g., fibrosing
cholestatic hepatitis) excluded
Kwo PY. NEJM 2014;371:2375-82CORAL-I
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