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

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

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.

Study Overview

• Status: Completed
• Conditions: End Stage Liver Disease; Hepatitis C
• Intervention / Treatment: Drug: Daclizumub; Drug: Tacrolimus; Drug: Cyclosporine; Drug: MMF

Detailed Description

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 If patients respond to treatment, the virus is no longer active.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.

• Study Type: Interventional
• Enrollment (Actual): 312
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • Texas
    • Dallas, Texas, United States, 75246
      • Baylor Regional Transplant Institute - Baylor University Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. 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.
2. Patient is a recipient of a primary whole/split, cadaveric/living donor liver transplant for end stage chronic Hepatitis C.
3. Patient is > age 18.
4. 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:

1. Patient has previously received or is receiving an organ transplant other than a liver.
2. Patient has received a liver transplant from a Hepatitis B core antibody or a Hepatitis C antibody positive donor.
3. Patient has received an ABO (blood group anti A, anti B antibodies) incompatible donor liver.
4. 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).
5. 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.
6. 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.
7. Recipient or donor is seropositive for human immunodeficiency virus (HIV) or HbsAg positive serology.
8. Patient is to receive antilymphocyte antibody induction therapy, such as ATGAM (lymphocyte immune globulin), OKT3 (muromonab-CD3), Simulect (basiliximab), or Thymoglobulin.
9. Patient has a known hypersensitivity to Prograf (TAC), HCO-60, CellCept (MMF), Zenapax or corticosteroids.
10. Patient is pregnant or lactating.
11. Patient has participated in a blinded trial or participated in a trial involving a non-marketed (investigational) drug within 3 months of enrollment.
12. 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.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Baylor Research Institute
• Collaborators: Medical University of South Carolina; University of Alabama at Birmingham; University of Chicago; New York University; Emory University; University of Southern California; Oregon Health and Science University; University of California, San Francisco; New York Presbyterian Hospital; University of Virginia; The University of Texas Health Science Center at San Antonio; University of Cincinnati; Lahey Clinic; Northwestern Memorial Hospital; University of Medicine and Dentistry of New Jersey; Baylor Health Care System; Mayo Clinic - Scottsdale/Phoenix, Arizona; Mayo Clinic - Rochester, Minnesota
• Investigators: Principal Investigator: Goran Klintmalm, MD, Baylor Univeristy Medical Center

Study record dates

Study Major Dates

• Study Start: July 1, 2002
• Primary Completion (Actual): April 1, 2006
• Study Completion (Actual): January 1, 2007

Study Registration Dates

• First Submitted: September 9, 2005
• First Submitted That Met QC Criteria: September 9, 2005
• First Posted (Estimate): September 14, 2005

Study Record Updates

• Last Update Posted (Estimate): January 12, 2017
• Last Update Submitted That Met QC Criteria: November 15, 2016
• Last Verified: November 1, 2016

More Information

Terms related to this study

• Keywords: Hepatitis C Virus; Immunosuppressive Agents
• Additional Relevant MeSH Terms: Digestive System Diseases; Liver Failure; Hepatic Insufficiency; RNA Virus Infections; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Flaviviridae Infections; Hepatitis, Viral, Human; Enterovirus Infections; Picornaviridae Infections; Hepatitis, Chronic; Liver Diseases; End Stage Liver Disease; Hepatitis; Hepatitis A; Hepatitis C; Hepatitis C, Chronic; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Antirheumatic Agents; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Dermatologic Agents; Anti-Bacterial Agents; Antibiotics, Antineoplastic; Antifungal Agents; Antitubercular Agents; Antibiotics, Antitubercular; Calcineurin Inhibitors; Tacrolimus; Mycophenolic Acid; Cyclosporine; Cyclosporins
• Other Study ID Numbers: 02-01-L; ZEN159 (Other Identifier: Baylor Research Institute)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: No their is not a plan to make individual Participant data available