rATG Induction and Tacrolimus Monotherapy in Pediatric Liver Transplantation

NCT01207141 | Completed DMC

• 2 other identifiers: 06080061R01AI073895-01
• Study Type: observational
• Target: 110
• Locations: 1 country
• Sites: 1

Brief Summary

This open-label clinical trial will evaluate the pharmacodynamics, pharmacogenomics and early efficacy and safety of steroid-free Tacrolimus (TAC) monotherapy and its minimization after induction with rabbit, anti-human thymocyte globulin (rATG, Genzyme, Cambridge, MA) in children and adults with pediatric liver transplantation. Eighty subjects (0-21 years) receiving liver transplantation will be enrolled. Incidence and severity of biopsy-proven acute cellular rejection (ACR) is a primary endpoint as well as time to Tacrolimus whole blood concentrations \<8 ng/ml The expected incidence of ACR is 50% and is derived from a non-consecutive subject population (n=40) who received an identical regimen in IND 64555. This incidence is acceptable because the long term sequel of rejection reported with other allografts have not been observed in liver grafts during IND 64555. These risks are further negated by the unique regenerative capacity of the liver allograft. An OBSERVATIONAL arm is being included in this trial. Because the numbers of pediatric liver transplants (LTx) are small in any single center setting, no information is known about relative outcomes on a conventional protocol, in children receiving conventional protocol of steroids+Tacrolimus. The PURPOSE of this additional recruitment is OBSERVATIONAL, only. Therefore, these subjects will NOT be randomized. Rather, by studying all types of patients, the investigators hope to utilize maximally, all available subjects, to understand the relative place of monotherapeutic induction. In turn, this will be the basis for a follow-up comparative, randomized trial.

Conditions

Liver Transplantation; Thymoglobulin; Rejection

Keywords

Liver Transplantation; Thymoglobulin; Rejection

Outcome Measures

Primary Outcomes (1)

• Incidence and severity of biopsy-proven acute cellular rejection

  90 days

Secondary Outcomes (2)

• Time to Tacrolimus whole blood concentrations <8 ng/ml

  1 year

• Duration of steroid treatment and time to steroid elimination

  1 year

Study Arms (2)

rATG induction

Liver transplant recipients who receive induction with rATG prior to transplantation.

no rATG induction

Liver transplant recipients who do not receive rATG induction therapy prior to transplantation.

Eligibility Criteria

• Age: Up to 21 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)
• Sampling Method: Non-Probability Sample

Study Population

Children 0- 21 years receiving liver transplantation

You may qualify if:

• Age 0-21 years, male and female
• Primary OLTx, Whole/segmental, cadaveric/live, Re-LTx, and LTx in the setting of a previous or simultaneous kidney transplant.
• All children receiving the types of LTx described above, but on conventional immunosuppression, will be enrolled in an observational arm, with the same treatment and monitoring protocols.

You may not qualify if:

• Multiorgan transplants (liver-intestine, liver intestine with stomach and other organs)
• Documented non-compliance
• Donor: Age \>60, macrovesicular steatosis \> 30%, Hepatitis C and B infections defined as anti-HCV antibody positive, and anti-Hepatitis B surface antigen or Hepatitis B core antibody positive, malignancy, cold ischemia time \>16 hours
• Children of child-bearing age receive pregnancy testing at the time of transplantation. Pregnancy is a contraindication to liver transplantation and therefore to enrollment in this clinical trial.

Sponsors & Collaborators

• University of Pittsburgh: lead
• National Institute of Allergy and Infectious Diseases (NIAID): collaborator

Study Sites (1)

Children's Hospital of Pittsburgh of UPMC

Pittsburgh, Pennsylvania, 15213, United States

Location

Biospecimen

Retention: NONE RETAINED

Blood

MeSH Terms

Conditions

Rejection, Psychology

Condition Hierarchy (Ancestors)

Social Behavior; Behavior

Study Officials

• Rakesh Sindhi, MD

  University of Pittsburgh

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Surgery

Study Record Dates

• First Submitted: September 21, 2010
• First Posted: September 22, 2010
• Study Start: August 1, 2006
• Primary Completion: May 1, 2019
• Study Completion: May 1, 2019
• Last Updated: March 7, 2023

Record last verified: 2023-03

Locations

US (1)