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

NCT00375895 | Terminated Phase 3

• 3 other identifiers: EudraCT 2006-002714-35LOC/06-05CIC0203/058
• Study Type: interventional
• Target: 11
• Locations: 1 country
• Sites: 13

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.

Conditions

Chronic Hepatitis C; Evidence of Liver Transplantation

Keywords

Cyclosporin; Peginterferon; Ribavirin; Chronic hepatitis C; Liver transplantation

Outcome Measures

Primary Outcomes (1)

• Prolonged virological response

  Percentage of patients with a negative qualitative PCR, 19 months after the initiation of cyclosporin treatment.

  19 months

Secondary Outcomes (8)

• Virological response 4, 7 and 13 months after the initiation of cyclosporin treatment

  4, 7 and 13 months

• Histological response: METAVIR score at 19 months

  19 months

• Biological response: liver function at 4, 7, 13 and 19 months

  4, 7, 13 and 19 months

• Incidence of acute or chronic graft rejection at 19 months

  19 months

• Incidence of death, graft loss and retransplantation at 13 and 19 months

  13 and 19 months

Study Arms (1)

Ciclosporin

EXPERIMENTAL

Drug: ciclosporin

Interventions

ciclosporin 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.

Also known as: CsA, Cyclosporin

Ciclosporin

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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),
• Having given a written informed consent.

You may not qualify if:

• Severe hepatocellular failure or decompensated cirrhosis,
• 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.

Sponsors & Collaborators

• Rennes University Hospital: lead
• Novartis: collaborator

Study Sites (13)

Service d'Hépatologie - Hôpital Jean Minjoz

Besançon, 25030, France

Location

Service d'Hépatogastroentérologie - Hôpital Beaujon

Clichy, 92118, France

Location

Service d'Hépatologie et Gastroentérologie - CH Henri Mondor

Créteil, 94010, France

Location

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

Lille, 59037, France

Location

Service de Chirurgie Générale - Hôpital Edouard Herriot

Lyon, 69437, France

Location

Chirurgie Générale - Hôpital de la Conception

Marseille, 13385, France

Location

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

Montpellier, 34295, France

Location

Chirurgie Viscérale et Digestive - Hôpital de l'Archet

Nice, 06200, France

Location

Service de Chirurgie Générale - Hôpital Cochin

Paris, 75679, France

Location

Service des Maladies du Foie - Hôpital Pontchaillou

Rennes, 35033, France

Location

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

Strasbourg, 67098, France

Location

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

Toulouse, 31403, France

Location

Centre Hépato-Biliaire - Hôpital Paul Brousse

Villejuif, 94804, France

Location

MeSH Terms

Conditions

Hepatitis C, Chronic

Interventions

Cyclosporine

Condition Hierarchy (Ancestors)

Hepatitis C; Blood-Borne Infections; Communicable Diseases; Infections; Hepatitis, Viral, Human; Virus Diseases; Flaviviridae Infections; RNA Virus Infections; Hepatitis, Chronic; Hepatitis; Liver Diseases; Digestive System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Cyclosporins; Peptides, Cyclic; Macrocyclic Compounds; Polycyclic Compounds; Peptides; Amino Acids, Peptides, and Proteins

Study Officials

• Yvon Calmus, MD, PhD

  Hôpital Cochin, Paris

  PRINCIPAL INVESTIGATOR

• Eric Bellissant, MD, PhD

  CHU Rennes

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 12, 2006
• First Posted: September 13, 2006
• Study Start: June 1, 2006
• Primary Completion: October 1, 2008
• Study Completion: December 1, 2009
• Last Updated: March 2, 2012

Record last verified: 2012-03

Locations

FR (13)