Hepatitis C, Liver Transplantation
Conditions
Brief summary
Pilot, single center, open-label study to evaluate the efficacy and tolerability of Grazoprevir and Elbasvir in HCV GT1 and 4 liver transplant recipients.30 liver transplant recipients with hepatitis C recurrence.
Interventions
DRUGGrazoprevir 100 mg/day
Grazoprevir 100 mg/ day 12 weeks
DRUGElbasvir 50 mg/d
Elbasvir 50 mg/day 12 weeks
DRUGRibavirin 1200 mg/day
Ribavirin 1200 mg/day 16 weeks
DRUGElbasvir 50 mg/day
Elbasvir 50 mg/d 16 weeks
Sponsors
Fundacion Clinic per a la Recerca Biomédica
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 78 Years
Healthy volunteers
No
Inclusion criteria
* Age between 18 and 78 year-old. * Previous liver transplantation(more than 6 month). * Genotype 1 and 4 infection. * Hepatitis C recurrence defined by the presence of abnormal liver function test, positive HCV-RNA, histological signs of hepatitis C recurrence. * Viral load ≥10000UI/mL. * Immunosuppression with tacrolimus and/or mycophenolate (Prednisone use is allowed at low dose, ≤10 mg/d). * Treatment naïve or treatment experienced (Peg-RBV or triple therapy).
Exclusion criteria
* Genotype 2, 3, 5 or 6 infection. * Decompensated cirrhosis defined by the presence of actual or previous history of clinical decompensation including ascites, hepatic encephalopathy, variceal bleeding or spontaneous bacterial peritonitis, or a Child-Pugh B or C. * Hepatocellular carcinoma after liver transplantation. * Total bilirubin \> 3 mg/dL. * Immunosuppression with cyclosporine or an mTOR inhibitor (everolimus or sirolimus). * Severe extrahepatic diseases: cardiovascular, respiratory, cerebrovascular and poorly controlled diabetes. * Platelets \< 75 x 109 cells/L. * Neutrophil count \< 0.5 x 109 cells/L. * Hemoglobin \< 9 g/dL. * Albumin \< 3g/dL. * HIV infection. * Hepatitis B infection. * Active intake of toxic amounts of alcohol or recreational drugs. * Females who are pregnant, become to be pregnant or breastfeeding or males whose partners are pregnant, become to be pregnant or breastfeeding. * Intake of disallowed medications including(but not limited to): 1. Antibiotics: clarithromycin, erythromycin, telithromycin, nafcillin, rifampin 2. Antifungals: itraconazole, ketoconazole, voriconazole 3. Antihypertensives: nifedipine 4. Anticonvulsants: carbamazepine, phenytoin, phenobarbital 5. Bosentan 6. Modafinil 7. St.Jonh's Wort 8. Immunosuppressants: cyclosporin, everolimus, sirolimus 9. Diabetes agents: glibenclamide, glyburide 10. Lipid lowering agents: gemfibrozil 11. Eltrombopag 12. Lapatinib 13. HIV medications: efavirenz, etravirine, all ritonavir boosted and unboosted HIV protease inhibitors 14. Statins: simvastatin, fluvastatin, rosuvastatin at doses greater than 10 mg/d, atorvastatin at doses greater than 10 mg/d.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Sustained virological response | 12 weeks post-treatment | Sustained virological response 12 w (SVR24) defined as HCV-RNA undetectable at post-treatment week 12. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Sustained virological response | 4 weeks and 24 weeks post-treatment | Sustained virological response 12 ( SVR12) defined as HCV-RNA undetectable at post-treatment weeks 4 and , 24 respectively. |
| To evaluate the beneficial effects of antiviral therapy on renal function. | 24 weeks post-treatment | creatinine sample analyses blood analyses in all visits |
| To assess the impact of therapy in kidney function. | 24 weeks post-treatment | Elevation Transaminases blood analyses in all visits |
| Tolerability of this combination in liver transplant recipients. | Every visit | Serious advers events evaluation |
Outcome results
None listed