Immunosuppression Withdrawal for Stable Pediatric Liver Transplant Recipients

This study is currently recruiting participants.
Verified December 2013 by National Institute of Allergy and Infectious Diseases (NIAID)
Immune Tolerance Network (ITN)
Information provided by (Responsible Party):
National Institute of Allergy and Infectious Diseases (NIAID) Identifier:
First received: July 9, 2012
Last updated: December 3, 2013
Last verified: December 2013

Anti-rejection medicines, also known as immunosuppressive drugs, are prescribed to organ transplant recipients to prevent rejection of the new organ. Long-term use of these medicines places transplant recipients at higher risk of serious infections and certain types of cancer.

This study seeks to:

  • Find out if it is safe to slowly reduce and then completely stop the immunosuppression taken by children who have received liver transplants. This process is called 'immunosuppression withdrawal'or ISW.
  • Find blood or liver biopsy tests that can help transplant doctors in the future to predict if it is safe to decrease or stop immunosuppression drugs in children who have had a liver transplant.

Condition Intervention Phase
Transplantation, Liver
Other: Immunosuppression withdrawal (ISW)
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment

Resource links provided by NLM:

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

Primary Outcome Measures:
  • Proportion of subjects with normal liver biopsy and test results [ Time Frame: 12 months post-IS withdrawal ] [ Designated as safety issue: Yes ]
    The proportion of participants that is operationally tolerant, defined as those who successfully withdraw from IS and maintain normal allograft status as assessed by liver biopsy and liver tests 12 months after complete ISW.

Secondary Outcome Measures:
  • Composite of refractory acute rejection (AR), chronic rejection (CR), requirement for retransplantation, or death [ Time Frame: 48 months ] [ Designated as safety issue: Yes ]
    Rate of a composite outcome measure defined as the proportion of participants who develop refractory AR, chronic rejection (CR), undergo retransplantation,or die during study participation.

  • Histologic severity of AR episodes according to Banff criteria [ Time Frame: 48 months ] [ Designated as safety issue: Yes ]
  • Clinical severity of AR episodes assessed by treatment and time necessary to resolve AR or allograft dysfunction [ Time Frame: 48 months ] [ Designated as safety issue: Yes ]
  • Histologic progression determined from the stage of fibrosis at baseline to completion of the study according to the Ishak Severity System [ Time Frame: 48 months ] [ Designated as safety issue: Yes ]
  • Durability of operational tolerance defined as the time from achievement of the primary endpoint to IS reinitiation or to the end of trial participation [ Time Frame: 48 months ] [ Designated as safety issue: No ]
  • Percent of IS dose reduction achieved prior to failing the primary endpoint for any reason [ Time Frame: 24 months ] [ Designated as safety issue: No ]
  • Percent of IS dose reduction in IS dose for those who fail to achieve the primary endpoint [ Time Frame: 24 months ] [ Designated as safety issue: No ]

Estimated Enrollment: 100
Study Start Date: August 2012
Estimated Study Completion Date: July 2017
Estimated Primary Completion Date: July 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: ISW Other: Immunosuppression withdrawal (ISW)
Participants will undergo gradual ISW in no less than 36 weeks and no more than 52 weeks with frequent monitoring of liver tests. All participants will be followed for 48 months ensuring a minimum of 36 months of follow-up after successful ISW.


Ages Eligible for Study:   up to 18 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Subject and/or parent guardian must be able to understand and provide informed consent;
  • Is the recipient of a living or deceased donor liver tx when subject was less than or equal to 6 years of age;
  • Is at least 4 years post-tx at the time of study enrollment;
  • Has normal allograft function defined as Alanine aminotransferase (ALT) < 50 IU/l and gamma-glutamyl transferase (GGT) < 50 IU/l;
  • Has no evidence of AR or CR within the past 2 years, based on medical history;
  • Is stable on IS monotherapy with a calcineurin inhibitor (CNI);
  • For female subjects of childbearing potential, subject must have a negative pregnancy test upon study entry;
  • For female and male subjects with reproductive potential, subject must agree to use FDA approved methods of birth control for the duration of the study;
  • Must be negative for HBV and HCV infection within one year of enrollment;
  • Must have screening biopsy that fulfills, based on central pathology reading,

Exclusion Criteria:

  • Have received a liver tx for autoimmune liver disease, including autoimmune hepatitis or primary sclerosing cholangitis;
  • Have received a liver tx for hepatitis B or hepatitis C;
  • Have received a second organ transplant before, simultaneously, or after liver tx;
  • Have a calculated GFR (modified Schwartz formula) of less than 60 mL/min/1.73 m2;
  • Have had a 50% dose increase in CNI within 6 months of screening;
  • Have discontinued a second IS agent within 12 months of screening;
  • Have any systemic illness requiring or likely to require chronic or recurrent use of IS;
  • Is pregnant or breastfeeding;
  • Is unwilling or unable to adhere with study requirements and procedures;
  • Have mental illness or history of drug or alcohol abuse that, in the opinion of the investigator, would interfere with the participant's ability to comply with study requirements;
  • Is unwilling or unable to provide consent or comply with the study protocol;
  • Has used investigational drugs within 4 weeks of enrollment;
  • Is receiving treatment for HIV infection;
  • Has received any licensed or investigational live attenuated vaccine(s) within two months of enrollment;
  • Has any medical condition that, in the opinion of the investigator, will interfere with safe participation in the trial.
  Contacts and Locations
Please refer to this study by its identifier: NCT01638559

Contact: Sharon Blaschka 415-476-3229

United States, California
University of California Recruiting
San Francisco, California, United States, 94143-0780
Contact: Sharon Blaschka    415-476-3229   
Principal Investigator: S Feng, MD, PhD         
United States, Colorado
Children's Hospital of Colorado Recruiting
Aurora, Colorado, United States, 80045
Contact: Susanna Burr   
Principal Investigator: Michael Narkewicz, M.D.         
United States, Georgia
Emory University and Children's Hospital of Atlanta Recruiting
Atlanta, Georgia, United States, 30322
Contact: Liezl de la Cruz - Tracy    404-785-0421   
Principal Investigator: Stuart Knechtle, M.D.         
United States, Illinois
Ann & Robert H. Lurie Children's Hospital of Chicago Recruiting
Chicago, Illinois, United States, 60614
Contact: Adelaide Delute   
Principal Investigator: Udeme Ekong, M.D.         
United States, Michigan
University of Michigan C. S. Mott Children's Hospital Recruiting
Ann Arbor, Michigan, United States, 94143
Contact: Darlene McLean    734-615-3822   
Principal Investigator: John Magee, M.D.         
United States, Missouri
St. Louis Children's Hospital - Washington University Recruiting
St. Louis, Missouri, United States, 63110
Contact: Stacy Postma    314-747-5931   
Principal Investigator: Yumirle Turmelle, M.D.         
United States, New York
New York Presbyterian Morgan Stanley Children's Hospital - Columbia University Medical Center Recruiting
New York, New York, United States, 10032
Contact: Stephanie Ringelstein    212-305-3839   
Principal Investigator: Steven Lobritto, M.D.         
United States, Ohio
Cincinnati Children's Hospital Recruiting
Cincinnati, Ohio, United States, 45229
Contact: Andre Hawkins    513-636-7511   
Principal Investigator: John Bucuvalas, M.D.         
United States, Pennsylvania
Children's Hospital of Philadelphia Recruiting
Philadelphia, Pennsylvania, United States, 19104
Contact: Debbie Kawchak, MS, RD, LDN   
Principal Investigator: Elizabeth Rand, M.D.         
Children's Hospital of Pittsburgh Recruiting
Pittsburgh, Pennsylvania, United States, 15224
Contact: Amanda Brown    412-692-6692   
Principal Investigator: George Mazariegos, M.D.         
United States, Texas
Texas Children's Hospital Recruiting
Houston, Texas, United States
Contact: Julie Economides, RN    832-822-1519   
Principal Investigator: Ross W Shepherd, M.D., FRACP         
Canada, Ontario
The Hospital for Sick Children Recruiting
Toronto, Ontario, Canada, M5G1X8
Contact: Wardah Hannan    416-813-7654 ext 201594   
Principal Investigator: Vicky Ng, M.D.         
Sponsors and Collaborators
Immune Tolerance Network (ITN)
Principal Investigator: S Feng, M.D. , Ph.D. University of California, San Francisco
Study Chair: J Bucuvalas, M.D. Children's Hospital Medical Center, Cincinnati
  More Information

No publications provided

Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID) Identifier: NCT01638559     History of Changes
Other Study ID Numbers: DAIT iWITH, UO1AI100807
Study First Received: July 9, 2012
Last Updated: December 3, 2013
Health Authority: United States: Federal Government

Keywords provided by National Institute of Allergy and Infectious Diseases (NIAID):
immunosuppression withdrawal processed this record on April 23, 2014