search
Back to results

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

Primary Purpose

Chronic Hepatitis C, Evidence of Liver Transplantation

Status
Terminated
Phase
Phase 3
Locations
France
Study Type
Interventional
Intervention
ciclosporin
Sponsored by
Rennes University Hospital
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Chronic Hepatitis C focused on measuring Cyclosporin, Peginterferon, Ribavirin, Chronic hepatitis C, Liver transplantation

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • Service d'Hépatologie - Hôpital Jean Minjoz
  • Service d'Hépatogastroentérologie - Hôpital Beaujon
  • Service d'Hépatologie et Gastroentérologie - CH Henri Mondor
  • Service des Maladies de l'Appareil Digestif - CHRU Claude Huriez
  • Service de Chirurgie Générale - Hôpital Edouard Herriot
  • Chirurgie Générale - Hôpital de la Conception
  • Service d'Hépato-gastro-entérologie - Hôpital Saint Eloi
  • Chirurgie Viscérale et Digestive - Hôpital de l'Archet
  • Service de Chirurgie Générale - Hôpital Cochin
  • Service des Maladies du Foie - Hôpital Pontchaillou
  • Service de Chirurgie Générale et Transplantation Multi-organe - Hôpital de la Hautepierre
  • Service d'Hépato-gastro-entérologie - Hôpital de Rangueil
  • Centre Hépato-Biliaire - Hôpital Paul Brousse

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Ciclosporin

Arm Description

Outcomes

Primary Outcome Measures

Prolonged virological response
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
Percentage of patient with negative or decreased quantitative PCR
Histological response: METAVIR score at 19 months
Biological response: liver function at 4, 7, 13 and 19 months
Transaminases, gammaGT, alcalin phosphatase, total bilirubin.
Incidence of acute or chronic graft rejection at 19 months
Incidence of death, graft loss and retransplantation at 13 and 19 months
Renal function at 4, 7, 13 and 19 months
Creatinin clearance
Incidence of treatment discontinuation at 4, 7, 13 and 19 months
Incidence of adverse events (cancers in particular).

Full Information

First Posted
September 12, 2006
Last Updated
March 1, 2012
Sponsor
Rennes University Hospital
Collaborators
Novartis
search

1. Study Identification

Unique Protocol Identification Number
NCT00375895
Brief Title
Switch From Tacrolimus to Cyclosporin in the Treatment of Recurrent Hepatitis C After Liver Transplantation
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.
Study Type
Interventional

2. Study Status

Record Verification Date
March 2012
Overall Recruitment Status
Terminated
Why Stopped
Insufficient enrollment
Study Start Date
June 2006 (undefined)
Primary Completion Date
October 2008 (Actual)
Study Completion Date
December 2009 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Rennes University Hospital
Collaborators
Novartis

4. Oversight

Data Monitoring Committee
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Chronic Hepatitis C, Evidence of Liver Transplantation
Keywords
Cyclosporin, Peginterferon, Ribavirin, Chronic hepatitis C, Liver transplantation

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
11 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Ciclosporin
Arm Type
Experimental
Intervention Type
Drug
Intervention Name(s)
ciclosporin
Other Intervention Name(s)
CsA, Cyclosporin
Intervention Description
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.
Primary Outcome Measure Information:
Title
Prolonged virological response
Description
Percentage of patients with a negative qualitative PCR, 19 months after the initiation of cyclosporin treatment.
Time Frame
19 months
Secondary Outcome Measure Information:
Title
Virological response 4, 7 and 13 months after the initiation of cyclosporin treatment
Description
Percentage of patient with negative or decreased quantitative PCR
Time Frame
4, 7 and 13 months
Title
Histological response: METAVIR score at 19 months
Time Frame
19 months
Title
Biological response: liver function at 4, 7, 13 and 19 months
Description
Transaminases, gammaGT, alcalin phosphatase, total bilirubin.
Time Frame
4, 7, 13 and 19 months
Title
Incidence of acute or chronic graft rejection at 19 months
Time Frame
19 months
Title
Incidence of death, graft loss and retransplantation at 13 and 19 months
Time Frame
13 and 19 months
Title
Renal function at 4, 7, 13 and 19 months
Description
Creatinin clearance
Time Frame
4, 7, 13 and 19 months
Title
Incidence of treatment discontinuation at 4, 7, 13 and 19 months
Time Frame
4, 7, 13 and 19 months
Title
Incidence of adverse events (cancers in particular).
Time Frame
19 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Yvon Calmus, MD, PhD
Organizational Affiliation
Hôpital Cochin, Paris
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Eric Bellissant, MD, PhD
Organizational Affiliation
CHU Rennes
Official's Role
Study Chair
Facility Information:
Facility Name
Service d'Hépatologie - Hôpital Jean Minjoz
City
Besançon
ZIP/Postal Code
25030
Country
France
Facility Name
Service d'Hépatogastroentérologie - Hôpital Beaujon
City
Clichy
ZIP/Postal Code
92118
Country
France
Facility Name
Service d'Hépatologie et Gastroentérologie - CH Henri Mondor
City
Créteil
ZIP/Postal Code
94010
Country
France
Facility Name
Service des Maladies de l'Appareil Digestif - CHRU Claude Huriez
City
Lille
ZIP/Postal Code
59037
Country
France
Facility Name
Service de Chirurgie Générale - Hôpital Edouard Herriot
City
Lyon
ZIP/Postal Code
69437
Country
France
Facility Name
Chirurgie Générale - Hôpital de la Conception
City
Marseille
ZIP/Postal Code
13385
Country
France
Facility Name
Service d'Hépato-gastro-entérologie - Hôpital Saint Eloi
City
Montpellier
ZIP/Postal Code
34295
Country
France
Facility Name
Chirurgie Viscérale et Digestive - Hôpital de l'Archet
City
Nice
ZIP/Postal Code
06200
Country
France
Facility Name
Service de Chirurgie Générale - Hôpital Cochin
City
Paris
ZIP/Postal Code
75679
Country
France
Facility Name
Service des Maladies du Foie - Hôpital Pontchaillou
City
Rennes
ZIP/Postal Code
35033
Country
France
Facility Name
Service de Chirurgie Générale et Transplantation Multi-organe - Hôpital de la Hautepierre
City
Strasbourg
ZIP/Postal Code
67098
Country
France
Facility Name
Service d'Hépato-gastro-entérologie - Hôpital de Rangueil
City
Toulouse
ZIP/Postal Code
31403
Country
France
Facility Name
Centre Hépato-Biliaire - Hôpital Paul Brousse
City
Villejuif
ZIP/Postal Code
94804
Country
France

12. IPD Sharing Statement

Learn more about this trial

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

We'll reach out to this number within 24 hrs