Gradual Withdrawal of Immune System Suppressing Drugs in Patients Receiving a Liver Transplant - Full Text View

Sponsor:	National Institute of Allergy and Infectious Diseases (NIAID)
Collaborator:	Immune Tolerance Network (ITN)
Information provided by:	National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier:	NCT00135694

Purpose

In order to prevent organ rejection, patients receiving liver transplants currently require life-long treatment with immune system-suppressing medications to prevent the rejection of the transplanted liver. However, these medications can cause long-term side effects, such as infection, kidney problems, diabetes, and cancer. In patients infected with hepatitis C virus (HCV), these medications may increase the risk of HCV infection in the transplanted liver. The purpose of this study is to determine whether a slow withdrawal of immune system-suppressing medications is safe. The study will also look at whether slow withdrawal will help reduce the long-term side effects of immune system-suppressing medications and decrease the chance for HCV infection of the new liver in transplant patients with HCV.

Condition	Intervention	Phase
Hepatitis C Hepatitis C, Chronic Nonimmune Nonviral Causes of Liver Failure	Procedure: Continuous maintenance immunosuppressive therapy Procedure: Immunosuppression withdrawal Procedure: Liver transplant	Phase II

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Parallel Assignment Masking: Open Label Primary Purpose: Treatment
Official Title:	A Phase II Trial to Assess the Safety of Immunosuppression Withdrawal in Liver Transplant Recipients

Resource links provided by NLM:

MedlinePlus related topics: Hepatitis Hepatitis A Hepatitis C Liver Diseases Liver Transplantation

U.S. FDA Resources

Further study details as provided by National Institute of Allergy and Infectious Diseases (NIAID):

Primary Outcome Measures:

Proportion of participants with progression of hepatitis C-related liver disease, defined as Stage 4 or higher fibrosis on the Ishak scale [ Time Frame: In the 2 years following random assignment ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:

Tolerance induction [ Time Frame: 6 months following immunosuppression withdrawal ] [ Designated as safety issue: No ]
Laboratory tests indicative of successful withdrawal [ Time Frame: 6 months following immunosuppression withdrawal ] [ Designated as safety issue: No ]
Hepatitis C immune response and graft injury [ Time Frame: Random assignment to immunosuppression withdrawal ] [ Designated as safety issue: Yes ]
Definition of rejection profiles from laboratory tests [ Time Frame: Post-immunosuppression withdrawal ] [ Designated as safety issue: No ]

Estimated Enrollment:	275
Study Start Date:	October 2005
Estimated Study Completion Date:	October 2017
Estimated Primary Completion Date:	October 2014 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: 1 Liver transplant, followed by tapered withdrawal of immunosuppressive therapy over the course of 1 year	Procedure: Immunosuppression withdrawal Tapering occurs over a 1-year period Procedure: Liver transplant Occurs at study entry
Active Comparator: 2 Liver transplant, followed by maintenance doses of continuous immunosuppressive therapy over the course of 1 year	Procedure: Continuous maintenance immunosuppressive therapy May be cyclosporine, mycophenolate mofetil, or tacrolimus Procedure: Liver transplant Occurs at study entry

Detailed Description:

Following organ transplants, immunosuppressive medications are used to prevent the patient's immune system from rejecting the transplanted organ. In general, these antirejection medications are prescribed for the remainder of the transplant recipient's life. However, in patients infected with HCV, these same medications are believed to be associated with a rapid reoccurrence of HCV, which can lead to failure of the transplanted liver, severe hepatitis, cirrhosis, and other serious conditions. This study will evaluate how safe it is to slowly withdraw antirejection medications without the rejection of the transplanted liver in patients with HCV-related as well as nonimmune nonviral-related liver failure receiving a liver transplant. The study will also determine if the risk for HCV infection in the transplanted liver decreases with this regimen in the HCV cohort of patients.

Participants will undergo liver transplantation and receive immunosuppression medications consistent with current standard practices. Study participants will be treated with standard of care antirejection medications after transplant. This includes a 3-month course of corticosteroids and maintenance therapy with one or two antirejection medications (tacrolimus or cyclosporine and/or mycophenolate mofetil). Participants will be tapered off corticosteroids in the first 3 months but will continue maintenance immunosuppression for 1 year. Participants will be regularly monitored for recurrence of hepatitis and for evidence of allograft rejection.

One year after transplantation, participants who meet certain criteria for immunosuppressive withdrawal will be randomly assigned to either the immunosuppression withdrawal group or the control group. Only study participants who are taking one immunosuppressive drug will qualify for the random assignment. Participants assigned to the drug withdrawal group will have their dose of immunosuppressive drug tapered off over the course of 1 year. The control group will be maintained on normal levels of their assigned immunosuppressive drugs. Immunosuppressive drugs will not be provided by this study.

During and after the withdrawal phase, participants will be closely monitored for liver function, signs of rejection, levels of HCV in the blood and liver, and for the response of the immune system to the withdrawal of immunosuppression. Participants will be followed for a minimum of 1 year after the completion of withdrawal, possibly up to 4 years.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Active hepatitis C virus (HCV) infection with genotype 1 OR nonimmune, nonviral liver disease
Needs liver transplant
Willing to use acceptable forms of contraception

Exclusion Criteria:

Previous transplant
Multiorgan or split liver transplant other than a right trisegment
Living donor transplant
Donor liver from a donor positive for antibody against hepatitis B core antigen
Donor liver from a donor positive for antibody against hepatitis C
Donor liver from a non-heart-beating donor
Liver failure due to autoimmune disease
Fulminant liver failure
Hepatitis B virus infection or HCV infection with a genotype other than genotype 1
Stage III or higher hepatocellular cancer
History of cancer. Patients with hepatocellular cancer, adequately treated in situ cervical carcinoma, adequately treated basal or squamous cell carcinoma of skin, or other cancer judged to have a 5-year risk of recurrence less than 10% are not excluded.
Active systemic infection at the time of transplantation
Clinically significant chronic kidney disease
Clinically significant cardiovascular or cerebrovascular disease
HIV infected
Pregnancy

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00135694

Locations

United States, California
University of California, San Francisco
San Francisco, California, United States, 94143
United States, Colorado
University of Colorado
Denver, Colorado, United States, 80262
United States, Illinois
Northwestern University
Chicago, Illinois, United States, 60208
United States, Michigan
University of Michigan
Ann Arbor, Michigan, United States, 48109
United States, Ohio
Cleveland Clinic
Cleveland, Ohio, United States, 44195
United States, Pennsylvania
University of Pennsylvania
Philadelphia, Pennsylvania, United States, 19104
United States, Texas
Baylor University
Dallas, Texas, United States, 76798
United States, Washington
University of Washington
Seattle, Washington, United States, 98195

Sponsors and Collaborators

National Institute of Allergy and Infectious Diseases (NIAID)

Immune Tolerance Network (ITN)

Investigators

Principal Investigator:

Abraham Shaked, MD, PhD

University of Pennsylvania

More Information

Additional Information:

Click here for the Immune Tolerance Network Web site This link exits the ClinicalTrials.gov site

No publications provided

Responsible Party:	Associate Director, Clinical Research Program, DAIT/NIAID
ClinicalTrials.gov Identifier:	NCT00135694 History of Changes
Other Study ID Numbers:	DAIT ITN030ST
Study First Received:	August 25, 2005
Last Updated:	October 25, 2011
Health Authority:	United States: Federal Government; United States: Institutional Review Board

Keywords provided by National Institute of Allergy and Infectious Diseases (NIAID):

hepatitis
hepatitis C
HCV
liver
liver disease
liver transplant

liver transplantation
transplant
hepatic
hepatic transplantation
immunosuppression
rejection

Additional relevant MeSH terms:

Hepatitis
Hepatitis A
Hepatitis C
Liver Failure
Hepatitis C, Chronic
Liver Diseases
Digestive System Diseases
Hepatitis, Viral, Human
Virus Diseases
Enterovirus Infections

Picornaviridae Infections
RNA Virus Infections
Flaviviridae Infections
Hepatic Insufficiency
Hepatitis, Chronic
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on February 13, 2012