rATG Induction and Tacrolimus Monotherapy in Pediatric Liver Transplantation
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.
|Study Design:||Observational Model: Cohort
Time Perspective: Prospective
|Official Title:||Pharmacodynamics, Pharmacogenomics, and Preliminary Safety and Efficacy of rATG Induction and Tacrolimus Monotherapy in Pediatric Liver Transplantation|
- Incidence and severity of biopsy-proven acute cellular rejection [ Time Frame: 90 days ] [ Designated as safety issue: No ]
- Time to Tacrolimus whole blood concentrations <8 ng/ml [ Time Frame: 1 year ] [ Designated as safety issue: No ]
- Duration of steroid treatment and time to steroid elimination [ Time Frame: 1 year ] [ Designated as safety issue: No ]
Biospecimen Retention: Samples With DNA
|Study Start Date:||August 2006|
|Estimated Study Completion Date:||December 2011|
|Estimated Primary Completion Date:||December 2010 (Final data collection date for primary outcome measure)|
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.
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|United States, Pennsylvania|
|Children's Hospital of Pittsburgh of UPMC|
|Pittsburgh, Pennsylvania, United States, 15213|
|Principal Investigator:||Rakesh Sindhi, MD||Children's Hospital of Pittsburgh of UPMC|