Switch From Tacrolimus to Cyclosporin in the Treatment of Recurrent Hepatitis C After Liver Transplantation

NCT ID: NCT00375895

Last Updated: 2012-03-02

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE3
• Total Enrollment: 11 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2006-06-30
• Study Completion Date: 2009-12-31

Brief Summary

In France, 50% of hepatitis C virus carriers develop chronic clinical hepatitis, which may lead to cirrhosis and liver transplantation. Transplant infection by hepatitis C virus is constant after transplantation and recurrence causes chronic liver disease in 50 to 80% of cases. The aim of this study is to assess the efficacy of cyclosporin on C virological response. Patients included in the Transpeg 1 study and non-responder or with a recurrent disease will be switched from their tacrolimus therapy to cyclosporin, in association with a 1 year peginterferon alfa-2a / ribavirin bitherapy. Efficacy will be assessed by the percentage of patients with a negative qualitative PCR after 19 months of cyclosporin treatment.

Detailed Description

In France, 50% of hepatitis C virus carriers develop chronic clinical hepatitis, which may lead to cirrhosis and liver transplantation. Transplant infection by hepatitis C virus is constant after transplantation. A main factor determining the severity of recurrent hepatitis C after transplantation may be immunosuppression. Thus optimization of immunosuppressive regimens might be a key aspect to improve the prognosis of chronic hepatitis C in transplanted patients. The two most frequently used immunosuppressive drugs are cyclosporin and tacrolimus. However, it has been shown that virus replication could be inhibited by cyclosporin, through the blockade of cyclophilins, decreasing hepatitis C viral load and improving liver function. These effects were not found with tacrolimus.

The aim of our study is to assess the efficacy on C virological response of the switch from tacrolimus to cyclosporin associated with a peginterferon alfa-2a / ribavirin bitherapy, in non-responder or with a recurrent VHC+ disease liver transplanted patients.

Patients will receive a 19 month cyclosporin treatment, associated during 12 months with a peginterferon alfa-2a / ribavirin bitherapy. Efficacy will be assessed by the percentage of patients with a negative qualitative PCR after 19 months of cyclosporin treatment.

Conditions

Chronic Hepatitis C; Evidence of Liver Transplantation

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Ciclosporin

Group Type: EXPERIMENTAL

ciclosporin

Intervention Type: DRUG

ciclosporin administered orally twice a day, at the initial dosing of 2.5 mg/kg/d, adjusted to obtain a C2 concentration of 600 ng/ml associated with the usual ribavirin and PEGinterferon bitherapy.

Interventions

ciclosporin

ciclosporin administered orally twice a day, at the initial dosing of 2.5 mg/kg/d, adjusted to obtain a C2 concentration of 600 ng/ml associated with the usual ribavirin and PEGinterferon bitherapy.

Intervention Type: DRUG

Other Intervention Names

CsA; Cyclosporin

Eligibility Criteria

Inclusion Criteria

• Adults aged 18 or over,
• Who had been included in the Transpeg 1 study,
• Non-responders after a three month peginterferon alfa-2a / ribavirin bitherapy or with a recurrent disease during the Transpeg 1 maintenance phase, whatever the randomization group (ribavirin or placebo),
• With a positive qualitative PCR at inclusion,
• With a METAVIR histologic score of 1 or more on the last biopsy (done within the 6 months preceding inclusion),
• Treated with tacrolimus for at least 6 months prior to inclusion,
• Having given a written informed consent.

Exclusion Criteria

• Treatment with peginterferon or ribavirin within the 6 months preceding inclusion,
• Severe hepatocellular failure or decompensated cirrhosis,
• Acute graft rejection within the two months preceding inclusion, or signs of chronic rejection on the last biopsy, or retransplantation since inclusion in the Transpeg 1 study,
• Treatment with cyclosporin for more than 6 months during the 24 months preceding inclusion,
• Treatment with a mTOR inhibitor or with another investigational immunosuppressive drug,
• Positive serology for HIV or HBV,
• Cancer (or history of other malignancy during the last 5 years) except patients transplanted for hepatocellular carcinoma and basocellular or excised spinocellular carcinoma,
• Serious concomitant disease or acute or chronic disorder, other than the current transplant, treated with steroids,
• Serious cardiac pathology within the last 6 months,
• Women with ongoing pregnancy or breast-feeding,
• Serious chronic renal failure (creatinine clearance < 30 ml/mn),
• Haemoglobin < 10 g/dl, platelets < 50 000/mm3 or neutrophils < 1000 / mm3,
• Abnormal TSH values,
• Inability to cooperate or to communicate with the investigator,
• Contraindications to ribavirin, peginterferon alfa-2a or cyclosporin.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Novartis

INDUSTRY

Sponsor Role: collaborator

Rennes University Hospital

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Yvon Calmus, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Hôpital Cochin, Paris

Eric Bellissant, MD, PhD

Role: STUDY_CHAIR

CHU Rennes

Locations

Service d'Hépatologie - Hôpital Jean Minjoz

Besançon, , France

Service d'Hépatogastroentérologie - Hôpital Beaujon

Clichy, , France

Service d'Hépatologie et Gastroentérologie - CH Henri Mondor

Créteil, , France

Service des Maladies de l'Appareil Digestif - CHRU Claude Huriez

Lille, , France

Service de Chirurgie Générale - Hôpital Edouard Herriot

Lyon, , France

Chirurgie Générale - Hôpital de la Conception

Marseille, , France

Service d'Hépato-gastro-entérologie - Hôpital Saint Eloi

Montpellier, , France

Chirurgie Viscérale et Digestive - Hôpital de l'Archet

Nice, , France

Service de Chirurgie Générale - Hôpital Cochin

Paris, , France

Service des Maladies du Foie - Hôpital Pontchaillou

Rennes, , France

Service de Chirurgie Générale et Transplantation Multi-organe - Hôpital de la Hautepierre

Strasbourg, , France

Service d'Hépato-gastro-entérologie - Hôpital de Rangueil

Toulouse, , France

Centre Hépato-Biliaire - Hôpital Paul Brousse

Villejuif, , France

Countries

France

Other Identifiers

LOC/06-05

Identifier Type: OTHER

Identifier Source: secondary_id

CIC0203/058

Identifier Type: -

Identifier Source: secondary_id

EudraCT 2006-002714-35

Identifier Type: -

Identifier Source: org_study_id