E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Recurrence of hepatitis C post-liver transplantation in patients with hepatitic C. |
Recidiva de la hepatitis C post-trasplante hepático en pacientes con hepatitic C. |
|
E.1.1.1 | Medical condition in easily understood language |
Recurrence of hepatitis C post-liver transplantation in patients with hepatitic C. |
Recidiva de la hepatitis C post-trasplante hepático en pacientes con hepatitic C. |
|
E.1.1.2 | Therapeutic area | Diseases [C] - Virus Diseases [C02] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10070678 |
E.1.2 | Term | Hepatitis C recurrent |
E.1.2 | System Organ Class | 10021881 - Infections and infestations |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10024716 |
E.1.2 | Term | Liver transplantation |
E.1.2 | System Organ Class | 10042613 - Surgical and medical procedures |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
Compare the evolution of hepatitis C recurrence as determined by progression of liver fibrosis (F ? 2, as ranked by ISHAK) a year post-liver transplantation in patients receiving low dose tacrolimus in combination with mycophenolate mofetil vs everolimus. |
Comparar la evolución de la recidiva de la hepatitis C determinada por progresión de la fibrosis hepática (F?2, según la clasificación de ISHAK) al año post-trasplante hepático en pacientes que reciben dosis bajas de tacrolimus en combinación con micofenolato mofetil vs everolimus. |
|
E.2.2 | Secondary objectives of the trial |
1. To assess the viral load of HCV RNA. 2. To characterize the haplotype of each patient. 3. Rate serological markers of hepatic fibrosis 4. To assess the elasticity of the liver parenchyma by FibroScan. 5. To compare the incidence of acute rejection and acute rejection corticoresistente. 6. Compare the time to first acute rejection episode. 7. Compare the need for antiviral therapy post-transplant year. 8. Assess patient survival and graft survival post-transplant year. 9. To evaluate the incidence of patient withdrawals or study discontinuation post-transplant year. 10. To evaluate the incidence of cardiovascular risk factors. |
1. Valorar la carga viral RNA del VHC. 2. Caracterizar el haplotipo de cada paciente. 3. Valorar los marcadores serológicos de fibrosis hepática 4. Valorar la elasticidad del parénquima hepático mediante FibroScan. 5. Comparar la incidencia del rechazo agudo y rechazo agudo corticoresistente. 6. Comparar el tiempo hasta el primer episodio de rechazo agudo. 7. Comparar la necesidad de administrar tratamiento antiviral al año post-trasplante. 8. Valorar la supervivencia del paciente y del injerto al año post-trasplante. 9. Valorar la incidencia de retiradas del paciente o interrupción del estudio al año post-trasplante. 10. Valorar la incidencia de los factores de riesgo cardiovascular. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Patients ? 18 years with HCV RNA-positive 12 months before transplantation, recipients of a first orthotopic liver transplantation. |
Pacientes ? 18 años, con RNA-VHC positivo 12 meses antes del trasplante, receptores de un primer trasplante hepático ortotópico. |
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E.4 | Principal exclusion criteria |
1. Multi-organ transplant recipients or who have previously received an organ transplant. 2. Patients with split or living donor recipients. 3. Transplant recipients with ABO incompatibility. 4. Patients seropositive for HIV antibodies. 5. Recipients who receive a transplant for fulminant hepatic failure. 6. HCV patients with cirrhosis who received antiviral treatment before transplantation, and have to negative serum HCV-RNA. 7. Patients with known malignancy or history of malignancy except basal cell skin carcinoma and hepatocellular carcinoma meeting the following criteria: absence of vascular invasion, lymph single or less than two inches in diameter or two or three nodules of no more than three inches in diameter (Milan criteria). 8. Patients with a glomerular filtration <60 ml/min/1.73m 2 before transplantation or requiring renal dialysis before transplantation. 9. Patients in whom severe coexisting disease, or suffering any unstable medical condition that could affect the objectives of the study. 10. Patients who have been treated during the month prior to inclusion in the study with a drug or therapy is not recorded (investigational drug) or if such therapy be administered in the post-transplant. 11. Pregnant patients, nursing or of childbearing potential, not using effective contraception. Exclusion criteria at the time of randomization (day 28 post-transplant): Patients who have not completed the healing process post-transplant month. Patients with a platelet count <50.000/mm3, a WBC count <2000/mm3, active infection requiring ICU admission or threatens vital, requiring intensive care and life support measures. |
1. Receptores de un trasplante multiorgánico o que hayan recibido previamente el trasplante de algún órgano. 2. Pacientes con split o receptores de donante vivo. 3. Receptores de un trasplante con incompatibilidad ABO. 4. Pacientes seropositivos para anticuerpos del VIH. 5. Receptores que reciban el trasplante por un fallo hepático fulminante. 6. Pacientes con cirrosis por VHC que hayan recibido tratamiento antiviral antes del trasplante, y que hayan negativizado el ARN-VHC sérico. 7. Pacientes con neoplasia conocida o historia de neoplasia, exceptuando carcinoma cutáneo de células basales y hepatocarcinoma que cumpla los siguientes criterios: ausencia de invasión vascular, nódulo único menor o igual a cinco centímetros de diámetro máximo o dos o tres nódulos de no más de tres centímetros de diámetro (criterios de Milán). 8. Pacientes con un Filtrado Glomerular <60 ml/min/1.73m 2 antes del trasplante, o que requieran diálisis renal antes del trasplante. 9. Pacientes en los que coexista una enfermedad grave, o que sufran alguna situación médica inestable, que pudiera afectar a los objetivos del estudio. 10. Pacientes que hayan sido tratados durante el mes previo a la inclusión en el estudio con algún fármaco o terapia no registrada (fármaco en investigación), o si dicha terapia se va a administrar en el post-trasplante. 11. Pacientes mujeres embarazadas, en periodo de lactancia o potencialmente fértiles, que no utilicen un método anticonceptivo eficaz. Criterios de exclusión en el momento de la randomización (día 28 post-trasplante): Pacientes que no han completado el proceso de cicatrización al mes post-trasplante. Pacientes con un recuento plaquetar <50.000/mm3, un recuento leucocitario <2.000/mm3, infección activa que requiera ingreso en UCI o suponga una amenaza vital, que requieran cuidados intensivos y medidas de soporte vital. |
|
E.5 End points |
E.5.1 | Primary end point(s) |
Percentage of patients with fibrosis grade ? 2 according to the classification of ISHAK |
Porcentaje de pacientes que presenten grado de fibrosis ? 2 según la clasificación de ISHAK |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
12 months after transplantation. |
12 meses postrasplante. |
|
E.5.2 | Secondary end point(s) |
Incidence of biopsy-proven acute rejection. Time to first episode of acute rejection. Time to histologic recurrence of hepatitis C after liver transplantation. Measures of central tendency and viral load of HCV. Patient survival and graft. Incidence of adverse events. |
Incidencia de rechazos agudos demostrados por biopsia. Tiempo hasta el primer episodio de rechazo agudo. Tiempo hasta la recidiva histológica de la hepatitis C post-trasplante. Medidas de centralización y dispersión de la carga viral del VHC. Supervivencia del paciente y del injerto. Incidencia de acontecimientos adversos. |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
12 months after transplantation. |
12 meses postrasplante. |
|
E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Yes |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
Last visit of the last subject undergoing the trial. |
Última visita del último sujeto del ensayo. |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 3 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 3 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |