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

This study has been terminated.
(Insufficient enrollment)
Sponsor:
Collaborator:
Novartis
Information provided by (Responsible Party):
Rennes University Hospital
ClinicalTrials.gov Identifier:
NCT00375895
First received: September 12, 2006
Last updated: March 1, 2012
Last verified: March 2012
  Purpose

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.


Condition Intervention Phase
Chronic Hepatitis C
Evidence of Liver Transplantation
Drug: ciclosporin
Phase 3

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Prospective, Open-label, Single Arm Pilot Study Evaluating the Effect on Virological Response of the Switch From Tacrolimus to Cyclosporin Associated With a Peginterferon Alfa-2a / Ribavirin Bitherapy, in Non-responder or With Recurrent VHC+ Disease Liver Transplanted Patients.

Resource links provided by NLM:


Further study details as provided by Rennes University Hospital:

Primary Outcome Measures:
  • Prolonged virological response [ Time Frame: 19 months ] [ Designated as safety issue: No ]
    Percentage of patients with a negative qualitative PCR, 19 months after the initiation of cyclosporin treatment.


Secondary Outcome Measures:
  • Virological response 4, 7 and 13 months after the initiation of cyclosporin treatment [ Time Frame: 4, 7 and 13 months ] [ Designated as safety issue: No ]
    Percentage of patient with negative or decreased quantitative PCR

  • Histological response: METAVIR score at 19 months [ Time Frame: 19 months ] [ Designated as safety issue: No ]
  • Biological response: liver function at 4, 7, 13 and 19 months [ Time Frame: 4, 7, 13 and 19 months ] [ Designated as safety issue: No ]
    Transaminases, gammaGT, alcalin phosphatase, total bilirubin.

  • Incidence of acute or chronic graft rejection at 19 months [ Time Frame: 19 months ] [ Designated as safety issue: No ]
  • Incidence of death, graft loss and retransplantation at 13 and 19 months [ Time Frame: 13 and 19 months ] [ Designated as safety issue: No ]
  • Renal function at 4, 7, 13 and 19 months [ Time Frame: 4, 7, 13 and 19 months ] [ Designated as safety issue: Yes ]
    Creatinin clearance

  • Incidence of treatment discontinuation at 4, 7, 13 and 19 months [ Time Frame: 4, 7, 13 and 19 months ] [ Designated as safety issue: Yes ]
  • Incidence of adverse events (cancers in particular). [ Time Frame: 19 months ] [ Designated as safety issue: Yes ]

Enrollment: 11
Study Start Date: June 2006
Study Completion Date: December 2009
Primary Completion Date: October 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Ciclosporin Drug: 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.
Other Names:
  • CsA
  • Cyclosporin

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00375895

Locations
France
Service d'Hépatologie - Hôpital Jean Minjoz
Besançon, France, 25030
Service d'Hépatogastroentérologie - Hôpital Beaujon
Clichy, France, 92118
Service d'Hépatologie et Gastroentérologie - CH Henri Mondor
Créteil, France, 94010
Service des Maladies de l'Appareil Digestif - CHRU Claude Huriez
Lille, France, 59037
Service de Chirurgie Générale - Hôpital Edouard Herriot
Lyon, France, 69437
Chirurgie Générale - Hôpital de la Conception
Marseille, France, 13385
Service d'Hépato-gastro-entérologie - Hôpital Saint Eloi
Montpellier, France, 34295
Chirurgie Viscérale et Digestive - Hôpital de l'Archet
Nice, France, 06200
Service de Chirurgie Générale - Hôpital Cochin
Paris, France, 75679
Service des Maladies du Foie - Hôpital Pontchaillou
Rennes, France, 35033
Service de Chirurgie Générale et Transplantation Multi-organe - Hôpital de la Hautepierre
Strasbourg, France, 67098
Service d'Hépato-gastro-entérologie - Hôpital de Rangueil
Toulouse, France, 31403
Centre Hépato-Biliaire - Hôpital Paul Brousse
Villejuif, France, 94804
Sponsors and Collaborators
Rennes University Hospital
Novartis
Investigators
Principal Investigator: Yvon Calmus, MD, PhD Hôpital Cochin, Paris
Study Chair: Eric Bellissant, MD, PhD CHU Rennes
  More Information

No publications provided

Responsible Party: Rennes University Hospital
ClinicalTrials.gov Identifier: NCT00375895     History of Changes
Other Study ID Numbers: EudraCT 2006-002714-35, LOC/06-05, CIC0203/058
Study First Received: September 12, 2006
Last Updated: March 1, 2012
Health Authority: France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)

Keywords provided by Rennes University Hospital:
Cyclosporin
Peginterferon
Ribavirin
Chronic hepatitis C
Liver transplantation

Additional relevant MeSH terms:
Hepatitis
Hepatitis A
Hepatitis, Chronic
Hepatitis C
Hepatitis C, Chronic
Liver Diseases
Digestive System Diseases
Hepatitis, Viral, Human
Virus Diseases
Enterovirus Infections
Picornaviridae Infections
RNA Virus Infections
Flaviviridae Infections
Cyclosporins
Cyclosporine
Tacrolimus
Peginterferon alfa-2a
Ribavirin
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antifungal Agents
Anti-Infective Agents
Therapeutic Uses
Dermatologic Agents
Antirheumatic Agents
Antimetabolites

ClinicalTrials.gov processed this record on August 27, 2014