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.
18 Years
N/A
Both
Chronic Hepatitis C, Evidence of Liver Transplantation
Trial Information
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. 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.
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.
Type of Study:
Interventional
Study Design:
Allocation: Non-Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Outcome Measure:
Prolonged virological response
Outcome Description:
Percentage of patients with a negative qualitative PCR, 19 months after the initiation of cyclosporin treatment.
Outcome Time Frame:
19 months
Safety Issue:
No
Principal Investigator
Yvon Calmus, MD, PhD
Investigator Role:
Principal Investigator
Investigator Affiliation:
Hôpital Cochin, Paris
Authority:
France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
Study ID:
EudraCT 2006-002714-35
NCT ID:
NCT00375895
Start Date:
June 2006
Completion Date:
December 2009
Related Keywords:
- Chronic Hepatitis C
- Evidence of Liver Transplantation
- Cyclosporin
- Peginterferon
- Ribavirin
- Chronic hepatitis C
- Liver transplantation
- Hepatitis
- Hepatitis A
- Hepatitis, Chronic
- Hepatitis C
- Hepatitis C, Chronic
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