Clinical trial NCT00694408: A Pilot Trial of Pediatric Liver Transplantation Without Steroids
Official title: A Randomized Pilot Trial of a Steroid-free Immunosuppressant Regimen in Pediatric Liver Transplantation
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Evidence of Liver Transplantation
Keywords: End stage liver disease
Paediatric liver transplantation
Steroid free immunosuppression
Lead sponsor: Birmingham Women's and Children's NHS Foundation Trust
Sponsor class: OTHER
Collaborators: name: Roche Pharma AG
First posted: 2008-06-10
Enrollment: 15
Sex: ALL
Minimum age (years): 1
Maximum age (years): 18
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Objective:

The overall objective is to investigate whether a steroid free immunosuppressive regimen is as safe and effective as a steroid containing regimen following pediatric liver transplantation and whether it promotes tolerance.

Detailed description: 3.2 Research question

Is it possible to avoid the use of corticosteroids in pediatric liver transplantation?

3.3 Trial objectives

This will be a pilot study to

i) investigate to what degree a steroid free immunosuppressive regimen is as safe and effective as a steroid containing regimen following pediatric liver transplantation

ii) investigate the effect of a steroid free immunosuppressive regimen on lymphocyte function and donor-specific immune responsiveness following pediatric liver transplantation

iii) investigate the effect of a steroid free immunosuppressive regimen on expression of tissue markers of tolerance following pediatric liver transplantation

It is hoped that this pilot study will be used to develop a definitive multicentre study of a steroid free regimen.

Eligibility criteria: Inclusion Criteria:

* Children undergoing primary isolated hepatic transplantation.
* Age \<=18 years
* Ability to provide informed consent

Exclusion Criteria:

* Children undergoing retransplantation.
* Transplantation for Intestinal failure associated liver disease.
* Multi-organ transplantation.
* Transplantation for autoimmune liver disease.
* Transplantation for extra hepatic malignancy.
* Pre-existing need for oral steroids, or high dose inhaled steroids sufficient to require a steroid warning card.

Primary outcomes:
measure: Primary endpoint: The development of histologically proven acute rejection. (within 12 months
timeFrame: 12m
Secondary outcomes:
measure: The development of steroid resistant acute rejection 12 months. The expression of tissue and circulating markers of immune tolerance in first year post transplant The incidence of infection in the first year post transplant
timeFrame: 12m
Other outcomes:
Locations:
city: Birmingham
country: United Kingdom
facility: Birmingham Children's Hospital
state: West Midlands
Study officials:
affiliation: Birmingham Children's Hospital
name: Patrick McKiernan, MRCP FRCPCH
role: PRINCIPAL_INVESTIGATOR
References:
citation: Sarwal MM, Vidhun JR, Alexander SR, Satterwhite T, Millan M, Salvatierra O Jr. Continued superior outcomes with modification and lengthened follow-up of a steroid-avoidance pilot with extended daclizumab induction in pediatric renal transplantation. Transplantation. 2003 Nov 15;76(9):1331-9. doi: 10.1097/01.TP.0000092950.54184.67.
citation: Vidhun JR, Sarwal MM. Corticosteroid avoidance in pediatric renal transplantation. Pediatr Nephrol. 2005 Mar;20(3):418-26. doi: 10.1007/s00467-004-1786-4. Epub 2005 Feb 3.
citation: Leonard H, Hornung T, Parry G, Dark JH. Pediatric cardiac transplant: results using a steroid-free maintenance regimen. Pediatr Transplant. 2003 Feb;7(1):59-63. doi: 10.1034/j.1399-3046.2003.00014.x.
citation: Walsh PT, Taylor DK, Turka LA. Tregs and transplantation tolerance. J Clin Invest. 2004 Nov;114(10):1398-403. doi: 10.1172/JCI23238.
citation: Yoshizawa A, Ito A, Li Y, Koshiba T, Sakaguchi S, Wood KJ, Tanaka K. The roles of CD25+CD4+ regulatory T cells in operational tolerance after living donor liver transplantation. Transplant Proc. 2005 Jan-Feb;37(1):37-9. doi: 10.1016/j.transproceed.2004.12.259.
citation: Hathaway M, Adams DH. Demonstration that donor-specific nonresponsiveness in human liver allograft recipients is both rare and transient. Transplantation. 2004 Apr 27;77(8):1246-52. doi: 10.1097/01.tp.0000121136.84965.35.
citation: Arora-Gupta N, Davies P, McKiernan P, Kelly DA. The effect of long-term calcineurin inhibitor therapy on renal function in children after liver transplantation. Pediatr Transplant. 2004 Apr;8(2):145-50. doi: 10.1046/j.1399-3046.2003.00132.x.
citation: Evans HM, McKiernan PJ, Kelly DA. Mycophenolate mofetil for renal dysfunction after pediatric liver transplantation. Transplantation. 2005 Jun 15;79(11):1575-80. doi: 10.1097/01.tp.0000163504.29054.3f.
citation: Kelly D, Jara P, Rodeck B, Lykavieris P, Burdelski M, Becker M, Gridelli B, Boillot O, Manzanares J, Reding R. Tacrolimus and steroids versus ciclosporin microemulsion, steroids, and azathioprine in children undergoing liver transplantation: randomised European multicentre trial. Lancet. 2004 Sep 18-24;364(9439):1054-61. doi: 10.1016/S0140-6736(04)17060-8.
citation: Reding R, Gras J, Sokal E, Otte JB, Davies HF. Steroid-free liver transplantation in children. Lancet. 2003 Dec 20;362(9401):2068-70. doi: 10.1016/S0140-6736(03)15104-5.