Study of Liver Transplant For End-Stage Liver Disease Caused By Chronic Hepatitis C Infection

Study Overview
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Brief Summary
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The purpose of this study is to compare three treatment regimens in patients who have received a liver transplant for end-stage liver disease caused by Chronic Hepatitis C infection.

Detailed Description
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End-stage liver disease due to Hepatitis C virus (HCV) infection is the most common reason for liver transplantation in the United States. Patients who have HCV will always carry the virus in their body. If patients respond to treatment, the virus is no longer active. This means that although the virus is still present, it is not currently causing damage to their liver. Because recurrence of HCV is virtually universal in HCV positive transplant recipients and is associated with long term, possibly lethal complications, the search for the most appropriate therapies must also include methods to prevent or minimize recurrence or disease progression, if the goal of improving long term outcomes for these patients is to be achieved. Corticosteroids and high doses of immunosuppressive agents have been associated with increased rates of HCV recurrence. Finding a regimen that provides adequate immunosuppression to prevent early and late rejection episodes, and minimizes steroid usage as well as high doses of other immunosuppressive agents is highly desirable. This study is being conducted to determine the most effective immunosuppressive regimen that will prevent allograft rejection, minimize adverse events and at the same time, prevent or reduce the incidence of HCV recurrence following liver transplant.

Official Title
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An Open-Label, Randomized, Prospective Multicenter Study To Compare The Efficacy And Safety Among 3 Immunosuppressant Treatment Regimens In Patients Receiving A Liver Transplant For ESLD Caused By Chronic Hepatitis C

Conditions
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End Stage Liver Disease, Hepatitis C

Intervention / Treatment
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* Drug: Daclizumub
* Drug: Tacrolimus
* Drug: Cyclosporine
* Drug: MMF


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patient has been fully informed and has signed an IRB approved informed consent form and is willing and able to follow study procedures for the full 2 years. Patient is a recipient of a primary whole/split, cadaveric/living donor liver transplant for end stage chronic Hepatitis C. Patient is > age 18. Female patients of child bearing potential must have a negative urine or serum pregnancy test upon hospitalization or within 7 days prior to enrollment and have agreed to utilize effective birth control throughout the study as well as for 6 weeks following study completion. Exclusion Criteria: Patient has previously received or is receiving an organ transplant other than a liver. Patient has received a liver transplant from a Hepatitis B core antibody or a Hepatitis C antibody positive donor. Patient has received an ABO (blood group anti A, anti B antibodies) incompatible donor liver. Patient has fulminant liver failure with a life expectancy without a liver transplant of less than 7 days as defined by UNOS (Adult Patient Status 1, UNOS Policy 3.6.4.1: See Appendix C). Patient has renal dysfunction pre-transplant that, in the opinion of the investigator, will prohibit the use of calcineurin inhibitors within 72 hours post transplant. Patient is intubated, on vasopressors, is ICU bound, or has experienced a significant blood loss (greater than 5 units) 72 hours prior to transplant procedure. Recipient or donor is seropositive for human immunodeficiency virus (HIV) or HbsAg positive serology. Patient is to receive antilymphocyte antibody induction therapy, such as ATGAM (lymphocyte immune globulin), OKT3 (muromonab-CD3), Simulect (basiliximab), or Thymoglobulin. Patient has a known hypersensitivity to Prograf (TAC), HCO-60, CellCept (MMF), Zenapax or corticosteroids. Patient is pregnant or lactating. Patient has participated in a blinded trial or participated in a trial involving a non-marketed (investigational) drug within 3 months of enrollment. Patient has participated in a trial involving a market drug within 30 days. However, patients who participated in any interferon or ribavirin trials are permitted.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: tacrolimus and cyclosporine<br>immunosuppressant treatment regimens the intervention is antirejection treatment with the above labeled drugs tacrolimus and cyclosporine | Drug: Daclizumub<br>* anti-rejection drug<br>* Other names: Zenapax;Drug: Tacrolimus<br>* anti rejection drug<br>* Other names: Prograf;|
| Active Comparator: MMF, tacrolimus and cyclosporine<br>immunosuppressant treatment regimensthe intervention is antirejection treatment with the above labeled drugs MMF tacrolimus and cyclosporine | Drug: Tacrolimus<br>* anti rejection drug<br>* Other names: Prograf;Drug: Cyclosporine<br>* anti rejection drug<br>* Other names: Neoral;Drug: MMF<br>* anti rejection drug<br>* Other names: mycophenolate mofetil;|
| Active Comparator: daclizumub, MMFand tacrolimus<br>immunosuppressant treatment regimens | Drug: Daclizumub<br>* anti-rejection drug<br>* Other names: Zenapax;Drug: Tacrolimus<br>* anti rejection drug<br>* Other names: Prograf;Drug: MMF<br>* anti rejection drug<br>* Other names: mycophenolate mofetil;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Freedom From Acute Rejection or HCV Recurrence or Treatment Failure | Freedom from acute rejection (Banff>grade 2 with RAI score>4) or freedom from HCV recurrence (Batts/Ludwig>Stage 2, or >Grade 3) that requires HCV antiviral therapy or treatment failure (patient death, graft loss, premature withdrawal from study regimen or treatment with more than 1 dose of corticosteroids for presumptive rejection without a biopsy to confirm the rejection; reported values represent the Number of participants with Freedom From Acute Rejection or HCV Recurrence or Treatment Failure | 12 months | 
| Freedom From HCV Recurrence Within First Year That Requires HCV Antiviral Therapy and Freedom From Treatment Failure | Participants would have their blood drawn and tested for the HCV virus to determine if they had recurrence | 12 month post transplant | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Hepatitis C Virus, Immunosuppressive Agents