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

September 12, 2006
March 1, 2012
June 2006
October 2008   (final data collection date for primary outcome measure)
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.
Prolonged virological response: percentage of patients with a negative qualitative PCR, 19 months after the initiation of cyclosporin treatment.
Complete list of historical versions of study NCT00375895 on ClinicalTrials.gov Archive Site
  • 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 ]
  • Virological response 4, 7 and 13 months after the initiation of cyclosporin treatment
  • Histological response: METAVIR score at 19 months
  • Biological response: liver function at 4, 7, 13 and 19 months
  • 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
  • Incidence of treatment discontinuation at 4, 7, 13 and 19 months
  • Incidence of adverse events (cancers in particular).
Not Provided
Not Provided
 
Switch From Tacrolimus to Cyclosporin in the Treatment of Recurrent Hepatitis C After Liver Transplantation
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.

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.

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.

Interventional
Phase 3
Allocation: Non-Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
  • Chronic Hepatitis C
  • Evidence of Liver Transplantation
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
Experimental: Ciclosporin
Intervention: Drug: ciclosporin
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Terminated
11
December 2009
October 2008   (final data collection date for primary outcome measure)

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.
Both
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
France
 
NCT00375895
EudraCT 2006-002714-35, LOC/06-05, CIC0203/058
No
Rennes University Hospital
Rennes University Hospital
Novartis
Principal Investigator: Yvon Calmus, MD, PhD Hôpital Cochin, Paris
Study Chair: Eric Bellissant, MD, PhD CHU Rennes
Rennes University Hospital
March 2012

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP