E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
DE NOVO LIVER TRANSPLANT |
TRAPIANTO DI FEGATO DE-NOVO |
|
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 | HLT |
E.1.2 | Classification code | 10019715 |
E.1.2 | Term | Hepatic viral infections |
E.1.2 | System Organ Class | 100000004871 |
|
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 |
To demonstrate that the rate of fibrosis stage 2 or above (Ishak-Knodell FS≥2) at 1 year posttransplant is lower in hepatitis C positive patients receiving Neoral versus tacrolimus. |
Dimostrare una piu` bassa incidenza di fibrosi di grado 2 o superiore (Ishak-Knodell FS≥2) in pazienti HCV+ in trattamento con Neoral versus tacrolimus ad un anno dal trapianto di fegato. |
|
E.2.2 | Secondary objectives of the trial |
¿ To compare the rate of the combined endpoint of death or graft loss or FS≥2 by 1 year post-transplant and at the 2 year follow-up visit; ¿ To compare the occurrence rate of FS≥2 at the 2 year follow-up visit ¿ To compare the mean fibrosis score at 1 and 2 years and its evolution over time in each arm ¿ To compare the percentage of patients with an increase of at least 1 stage in fibrosis between 1 and 2 years ¿ To compare the incidence of fibrosing cholestatic hepatitis by 1 year |
incidenza dell¿endpoint composito: morte,perdita d¿organo e FS≥2 ad 1 e 2 anni dal trapianto- confronto dei principali scores per la fibrosi ad 1 e 2 anni dal trapianto- confronto delle cinetiche virali ad 1 e 2 anni dal trapianto |
|
E.2.3 | Trial contains a sub-study | Yes |
E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
PHARMACOGENETIC: Vers:Finale Date:2005/06/22 Title: Objectives:
|
FARMACOGENETICA: Vers:Finale Data:2005/06/22 Titolo:STUDIO MULTICENTRICO, RANDOMIZZATO, IN APERTO PER CONFRONTARE LO SVILUPPO DI FIBROSI EPATICA 12 MESI DOPO TRAPIANTO DI FEGATO PER CIRROSI DA EPATITE C IN PAZIENTI IN TRATTAMENTO CON NEORAL O TACROLIMUS Obiettivi:Biopsia epatica: il campione bioptico di fegato rimanente (preferibilmente meta`) raccolto nel contesto dello studio principale sara` impiegato anche per l¿analisi farmacogenomica. Non saranno effettuate biopsie addizionali.
|
|
E.3 | Principal inclusion criteria |
¿ Male or female aged 18 to 75 (inclusive) ¿ Reason for transplant is end-stage liver disease due to hepatitis C cirrhosis ¿ Patients receiving a first liver transplant from a deceased or living donor ¿ Patients willing and capable of giving written informed consent for study participation ¿ Patients in whom allograft biopsies will be possible ¿ Patients in whom the immunosuppressive regimen described in this protocol will be initiated and maintained for the entire study period |
¿ Pazienti di entrambi i sessi, di eta` compresa tra 18 e 75 anni ¿ Trapianto di fegato dovuto ad una cirrosi da epatite C ¿ Primo trapianto di fegato da donatore vivente o cadavere ¿ Possibilita` di effettuare biopsie del fegato trapiantato ¿ Consenso informato scritto |
|
E.4 | Principal exclusion criteria |
¿ Multi-organ transplant recipients ¿ Transplanted with an organ from a non-heart beating donor ¿ Patients receiving an ABO incompatible liver ¿ Expected to receive induction therapy with ATG/ALG or OKT3 ¿ HBV/HIV co-infected patients ¿ Recipients of an organ from an HCV+ or HIV+ or HBV+ donor ¿ Patients with a serum creatinine ≥2.0 mg/dL (≥177 μmol/L) prior to transplantation or if renal dialysis is necessary prior to transplantation ¿ Patients with severe coexisting disease or presenting with any unstable medical condition which could affect the study objectives ¿ Patients who are not eligible to receive the recommended calcineurin inhibitor starting dose within 24 hours of transplantation ¿ Patients with a co-existing alcoholic disease who have not been abstinent for at least 6 month immediately prior to transplantation and are not expected to be able to remain abstinent after transplantation ¿ Patients who are unlikely to comply with the study requirements or unable to give informed consent ¿ Use of other investigational drugs at the time of enrollment, or within 30 days or 5 halflives of enrollment, whichever is longer or if such therapy is to be instituted posttransplantation ¿ History of hypersensitivity to any of the study drugs or to drugs with similar chemical structures ¿ Patients transplanted for hepatocellular carcinoma exceeding the Milan criteria, defined as presence of a tumor 5 cm or less in diameter in patients with single hepatocellular carcinoma and no more than 3 tumor nodules, each 3 cm or less in diameter in patients with multiple tumors ¿ History of malignancy of any organ system, treated or untreated, within the past 5 years whether or not there is evidence of local recurrence or metastases, with the exception of localized basal cell carcinoma of the skin ¿ Pregnant or nursing (lactating) women, where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive hCG laboratory test (> 5 mIU/ml) |
¿ Trapianto multiorgano o donatore a cuore non battente ¿ Incompatibilita` AB0 ¿ Terapia di induzione con ATG/ALG o OKT3 ¿ Paziente con infezione concomitante HBV o HIV oppure organi da donatori HCV+/HIV+/HBV+ ¿ Livelli di creatinina ≥2.0 mg/dL (≥177 μmol/L) o necessita` di dialisi prima del trapianto ¿ Pazienti alcolisti che non siano in stato di astinenza da almeno 6 mesi prima del trapianto e capaci di restare tali dopo il trapianto ¿ Trapianto per carcinomi epatocellulari che supera i criteri di Milano, definiti come presenza di un tumore di non oltre 5 cm di diametro in pazienti con carcinoma epatocellulare singolo e non oltre 3 noduli tumorali, ciascuno di diametro di non oltre 3 cm, in pazienti con tumori multipli ¿ Storia di neoplasie nei 5 anni precedenti il trapianto (ad eccezione di carcinomi cutanei basocellulari) ¿ Donne in gravidanza o in allattamento |
|
E.5 End points |
E.5.1 | Primary end point(s) |
To compare the development of liver fibrosis at 12 months after transplantation for hepatitis C cirrhosis |
Confrontare lo sviluppo di fibrosi epatica 12 mesi dopo trapianto di fegato per cirrosi da epatite C |
|
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 | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
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 | Yes |
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) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | Yes |
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
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 6 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 20 |
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
| |
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 0 |
E.8.9.1 | In the Member State concerned months | 96 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 0 |
E.8.9.2 | In all countries concerned by the trial months | 96 |
E.8.9.2 | In all countries concerned by the trial days | 0 |