A Pilot Trial of Pediatric Liver Transplantation Without Steroids

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ClinicalTrials.gov Identifier: NCT00694408

Recruitment Status : Terminated (Study terminated due to withdrawal from market of Daclizumab)

First Posted : June 10, 2008

Last Update Posted : January 20, 2017

Sponsor:

Collaborator:

Roche Pharma AG

Information provided by (Responsible Party):

Birmingham Women's and Children's NHS Foundation Trust

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Evidence of Liver Transplantation	Drug: methyl prednisolone, hydrocortisone, prednisolone Other: No steroids	Phase 3

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.

Study Design


Study Type :	Interventional (Clinical Trial)
Actual Enrollment :	15 participants
Allocation:	Randomized
Intervention Model:	Parallel Assignment
Masking:	None (Open Label)
Primary Purpose:	Treatment
Official Title:	A Randomized Pilot Trial of a Steroid-free Immunosuppressant Regimen in Pediatric Liver Transplantation
Study Start Date :	June 2008
Actual Primary Completion Date :	August 2011
Actual Study Completion Date :	August 2011

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Liver Transplantation

Drug Information available for: Hydrocortisone acetate Hydrocortisone Prednisolone Prednisolone acetate Methylprednisolone acetate Methylprednisolone Prednisolone sodium phosphate Hydrocortisone sodium succinate Prednisolone phosphate Hydrocortisone cypionate Prednisolone sodium succinate Methylprednisolone sodium succinate Hydrocortisone valerate Hydrocortisone probutate Proctofoam-HC

U.S. FDA Resources

Arms and Interventions

Arm	Intervention/treatment
Active Comparator: Steroid immunosuppressive regimen Freedom from rejection and safety in children undergoing paediatric liver transplant using steroid containing immunosuppression regimen post transplant. This group of patients will receive steroids in conjunction with other prescribed immunosuppressive agents. Intervention is use of methyl prednisolone, hydrocortisone, prednisolone as routine post transplant management	Drug: methyl prednisolone, hydrocortisone, prednisolone Will be specific dependant on weight of patients Other Name: Methylprednisolone;Hydrocortisone;Prednisolone
Active Comparator: Steroid free immunosuppressive regimen Freedom from rejection and safety in children undergoing paediatric liver transplant using steroid free immunosuppression regimen post transplant. The patients in this arm will receive immunosuppression but not steroids to compare with those treated with steroids to measure differences in rejection and safety of a steroid free immunosuppressive regimen. Intervention is omission of methyl prednisolone, hydrocortisone, prednisolone as routine post transplant management. No steroids will be used routinely in this arm	Other: No steroids Children undergoing primary liver transplant will receive monoclonal antibodies and tacrolimus as per protocol

Arm

Intervention/treatment

Active Comparator: Steroid immunosuppressive regimen

Freedom from rejection and safety in children undergoing paediatric liver transplant using steroid containing immunosuppression regimen post transplant. This group of patients will receive steroids in conjunction with other prescribed immunosuppressive agents. Intervention is use of methyl prednisolone, hydrocortisone, prednisolone as routine post transplant management

Drug: methyl prednisolone, hydrocortisone, prednisolone

Will be specific dependant on weight of patients

Other Name: Methylprednisolone;Hydrocortisone;Prednisolone

Active Comparator: Steroid free immunosuppressive regimen

Freedom from rejection and safety in children undergoing paediatric liver transplant using steroid free immunosuppression regimen post transplant. The patients in this arm will receive immunosuppression but not steroids to compare with those treated with steroids to measure differences in rejection and safety of a steroid free immunosuppressive regimen. Intervention is omission of methyl prednisolone, hydrocortisone, prednisolone as routine post transplant management. No steroids will be used routinely in this arm

Other: No steroids

Children undergoing primary liver transplant will receive monoclonal antibodies and tacrolimus as per protocol

Outcome Measures

Primary Outcome Measures :

Primary endpoint: The development of histologically proven acute rejection. (within 12 months [ Time Frame: 12m ]

Secondary Outcome Measures :

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 [ Time Frame: 12m ]

Eligibility Criteria

Information from the National Library of Medicine

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Ages Eligible for Study:	up to 18 Years (Child, Adult)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

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.

Contacts and Locations

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00694408

Locations


United Kingdom
Birmingham Children's Hospital
Birmingham, West Midlands, United Kingdom, B4 6NH

Sponsors and Collaborators

Birmingham Women's and Children's NHS Foundation Trust

Roche Pharma AG

Investigators


Principal Investigator:	Patrick McKiernan, MRCP FRCPCH	Birmingham Children's Hospital

More Information

Publications:

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.

Vidhun JR, Sarwal MM. Corticosteroid avoidance in pediatric renal transplantation. Pediatr Nephrol. 2005 Mar;20(3):418-26. Epub 2005 Feb 3. Review.

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.

Walsh PT, Taylor DK, Turka LA. Tregs and transplantation tolerance. J Clin Invest. 2004 Nov;114(10):1398-403. Review.

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.

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.

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.

Evans HM, McKiernan PJ, Kelly DA. Mycophenolate mofetil for renal dysfunction after pediatric liver transplantation. Transplantation. 2005 Jun 15;79(11):1575-80.

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.

Reding R, Gras J, Sokal E, Otte JB, Davies HF. Steroid-free liver transplantation in children. Lancet. 2003 Dec 20;362(9401):2068-70.


Responsible Party:	Birmingham Women's and Children's NHS Foundation Trust
ClinicalTrials.gov Identifier:	NCT00694408 History of Changes
Other Study ID Numbers:	SFPT/OL
First Posted:	June 10, 2008 Key Record Dates
Last Update Posted:	January 20, 2017
Last Verified:	January 2017

Keywords provided by Birmingham Women's and Children's NHS Foundation Trust:


End stage liver disease Paediatric liver transplantation Steroid free immunosuppression

Additional relevant MeSH terms:


Liver Extracts Prednisolone acetate Methylprednisolone acetate Hydrocortisone 17-butyrate 21-propionate Hydrocortisone acetate Cortisol succinate Prednisolone Methylprednisolone Methylprednisolone Hemisuccinate Hydrocortisone Prednisolone hemisuccinate Prednisolone phosphate Immunosuppressive Agents Hematinics	Anti-Inflammatory Agents Glucocorticoids Hormones Hormones, Hormone Substitutes, and Hormone Antagonists Physiological Effects of Drugs Antineoplastic Agents, Hormonal Antineoplastic Agents Antiemetics Autonomic Agents Peripheral Nervous System Agents Gastrointestinal Agents Neuroprotective Agents Protective Agents Immunologic Factors

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