Steroid Free Immunosuppression in Liver Transplantation - Full Text View

Purpose

The purpose of this study is to determine whether steroid-related complications can be avoided by using steroid-free immuno-suppressive drug regimen after liver transplantation.

Condition	Intervention	Phase
Liver Cirrhosis Liver Transplant Disorder	Drug: Steroids Drug: Basiliximab Drug: Tacrolimus Drug: Enteric-coated Mycophenolic acid (EC-MPA)	Phase 4

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Factorial Assignment Masking: Open Label Primary Purpose: Treatment
Official Title:	Steroid Free Immunosuppression in Liver Transplantation

Resource links provided by NLM:

Genetics Home Reference related topics: North American Indian childhood cirrhosis

MedlinePlus related topics: Cirrhosis Liver Transplantation Steroids

Drug Information available for: Prednisolone Prednisolone acetate Prednisone Methylprednisolone acetate Methylprednisolone Prednisolone sodium phosphate Prednisolone phosphate Prednisolone sodium succinate Methylprednisolone sodium succinate Mycophenolic acid Mycophenolate sodium Tacrolimus Mycophenolate mofetil hydrochloride Mycophenolate mofetil Basiliximab

U.S. FDA Resources

Further study details as provided by Thomas Jefferson University:

Primary Outcome Measures:

Graft Survival Rate [ Time Frame: 1 and 2 years ] [ Designated as safety issue: No ]
Percentage of recipients whose liver grafts are still working at the end of 1 and 2 years.
Patient Survival Rate [ Time Frame: 1 and 2 years ] [ Designated as safety issue: No ]
Percentage of recipients who are still alive at the end of 1 and 2 years.
Acute Rejection Rate [ Time Frame: 6 months post-transplant ] [ Designated as safety issue: Yes ]
Biopsy proven acute rejection defined by biochemical and histological changes as well as the need for temporary steroid use occurred in 1 patient in each group both of which were steroid responsive

Secondary Outcome Measures:

Infection as an Adverse Effect of Steroids [ Time Frame: 3 months post-transplant ] [ Designated as safety issue: Yes ]
Incidence of bacterial infection was similar in the control group as well as study group, 4 patients in both groups had infection
Incidence and Severity of HCV Recurrence Post-OLT [ Time Frame: 6 months post-transplant ] [ Designated as safety issue: No ]
The incidence and severity of HCV recurrence based on Hepatitis C PCR levels and protocol liver biopsy findings were found to be similar between the 2 groups.
New-onset Diabetes Mellitus (NODM) as Secondary Outcome [ Time Frame: 6 months ] [ Designated as safety issue: No ]
The incidence of new-onset Diabetes mellitus (NODM, based on percentage of previously non-diabetic patients who developed DM post-transplantation, was similar between the 2 groups.

Enrollment:	40
Study Start Date:	February 2006
Study Completion Date:	June 2008
Primary Completion Date:	May 2008 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Steroid -free immunosuppression Study group - Basiliximab, Tacrolimus, Enteric-coated Mycophenolic acid (EC-MPA)	Drug: Basiliximab Basiliximab shall be given as induction therapy at 20 mg IV bolus intra-operatively and on the 4th day after transplantation. Other Name: Simulect Drug: Tacrolimus Tacrolimus shall be used as the main maintenance immuno-suppressive drug. It will be given at a dose of 0.15mg/ kg/ day by mouth or through a naso-gastric tube (NGT), starting not earlier than 24 after the transplant but within 48 hrs after reperfusion. The dose shall be adjusted to achieve a trough level of 10-15 ng/ml during the first 30 days after transplantation and lowered to 5-10 ng/ml, thereafter. Other Name: Prograf Drug: Enteric-coated Mycophenolic acid (EC-MPA) This drug may be given in combination with calcineurin inhibitors (tacrolimus) and steroids for maintenance immuno-prophylaxis to prevent rejection. They are particularly useful in recipients with renal dysfunction and neurotoxicity, when there is a need to reduce dose or delay introduction of calcineurin inhibitors. This drug is given at 720 mg PO BID for 3 months. Other Name: Myfortic
Steroid containing immunosuppression Control group- Basiliximab, Tacrolimus, EC-MPA, steroids	Drug: Steroids Patients randomized to Control group shall be administered steroids as methylprednisolone (Solumedrol) 1000 mg IV during the anhepatic phase. Methylprednisolone will be continued according to the following taper schedule: 50 mg IV every 6 hrs on day 1; 40 mg IV every 6hrs on day 2; 30 mg IV every 6 hrs on day 3; 20 mg IV every 6 hrs on day 4; 20 mg IV every 12 hrs on day 5; and Prednisone 20 mg by mouth or Naso-gastric tube (NGT) on day 6. Prednisone shall be tapered slowly starting at 1 month post-OLT and weaned off completely by 6 months post-OLT. Other Names: Methylprednisolone (Solumedrol) Prednisone Drug: Basiliximab Basiliximab shall be given as induction therapy at 20 mg IV bolus intra-operatively and on the 4th day after transplantation. Other Name: Simulect Drug: Tacrolimus Tacrolimus shall be used as the main maintenance immuno-suppressive drug. It will be given at a dose of 0.15mg/ kg/ day by mouth or through a naso-gastric tube (NGT), starting not earlier than 24 after the transplant but within 48 hrs after reperfusion. The dose shall be adjusted to achieve a trough level of 10-15 ng/ml during the first 30 days after transplantation and lowered to 5-10 ng/ml, thereafter. Other Name: Prograf Drug: Enteric-coated Mycophenolic acid (EC-MPA) This drug may be given in combination with calcineurin inhibitors (tacrolimus) and steroids for maintenance immuno-prophylaxis to prevent rejection. They are particularly useful in recipients with renal dysfunction and neurotoxicity, when there is a need to reduce dose or delay introduction of calcineurin inhibitors. This drug is given at 720 mg PO BID for 3 months. Other Name: Myfortic

Arms

Assigned Interventions

Steroid -free immunosuppression

Study group - Basiliximab, Tacrolimus, Enteric-coated Mycophenolic acid (EC-MPA)

Drug: Basiliximab

Basiliximab shall be given as induction therapy at 20 mg IV bolus intra-operatively and on the 4th day after transplantation.

Other Name: Simulect

Drug: Tacrolimus

Tacrolimus shall be used as the main maintenance immuno-suppressive drug. It will be given at a dose of 0.15mg/ kg/ day by mouth or through a naso-gastric tube (NGT), starting not earlier than 24 after the transplant but within 48 hrs after reperfusion. The dose shall be adjusted to achieve a trough level of 10-15 ng/ml during the first 30 days after transplantation and lowered to 5-10 ng/ml, thereafter.

Other Name: Prograf

Drug: Enteric-coated Mycophenolic acid (EC-MPA)

This drug may be given in combination with calcineurin inhibitors (tacrolimus) and steroids for maintenance immuno-prophylaxis to prevent rejection. They are particularly useful in recipients with renal dysfunction and neurotoxicity, when there is a need to reduce dose or delay introduction of calcineurin inhibitors. This drug is given at 720 mg PO BID for 3 months.

Other Name: Myfortic

Steroid containing immunosuppression

Control group- Basiliximab, Tacrolimus, EC-MPA, steroids

Drug: Steroids

Patients randomized to Control group shall be administered steroids as methylprednisolone (Solumedrol) 1000 mg IV during the anhepatic phase. Methylprednisolone will be continued according to the following taper schedule: 50 mg IV every 6 hrs on day 1; 40 mg IV every 6hrs on day 2; 30 mg IV every 6 hrs on day 3; 20 mg IV every 6 hrs on day 4; 20 mg IV every 12 hrs on day 5; and Prednisone 20 mg by mouth or Naso-gastric tube (NGT) on day 6. Prednisone shall be tapered slowly starting at 1 month post-OLT and weaned off completely by 6 months post-OLT.

Other Names:

Methylprednisolone (Solumedrol)
Prednisone

Drug: Basiliximab

Basiliximab shall be given as induction therapy at 20 mg IV bolus intra-operatively and on the 4th day after transplantation.

Other Name: Simulect

Drug: Tacrolimus

Tacrolimus shall be used as the main maintenance immuno-suppressive drug. It will be given at a dose of 0.15mg/ kg/ day by mouth or through a naso-gastric tube (NGT), starting not earlier than 24 after the transplant but within 48 hrs after reperfusion. The dose shall be adjusted to achieve a trough level of 10-15 ng/ml during the first 30 days after transplantation and lowered to 5-10 ng/ml, thereafter.

Other Name: Prograf

Drug: Enteric-coated Mycophenolic acid (EC-MPA)

This drug may be given in combination with calcineurin inhibitors (tacrolimus) and steroids for maintenance immuno-prophylaxis to prevent rejection. They are particularly useful in recipients with renal dysfunction and neurotoxicity, when there is a need to reduce dose or delay introduction of calcineurin inhibitors. This drug is given at 720 mg PO BID for 3 months.

Other Name: Myfortic

Show Detailed Description

Eligibility

Ages Eligible for Study:	18 Years to 72 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Male and female patients between 18 and 72 years of age
Male or female patients who are primary cadaveric liver transplant recipients
Cold ischemia time must be <20 hours
Females capable of becoming pregnant must have a negative pregnancy test at baseline and are required to practice an approved method of birth control for the duration of the study and for a period of three months following discontinuation of study medication
Patient has given written informed consent to participate in the study

Exclusion Criteria:

Patients meeting any of the following criteria at baseline will be excluded from study participation
Patients who have previously received an organ transplant
Patients who are recipients of a multiple organ transplants
Women of childbearing potential not using the contraception method(s) specified in this study, as well as women who are breastfeeding
Known sensitivity to Simulect or class of Simulect
Patients with severe medical condition(s) that in the view of the investigator prohibits participation in the study
Use of any other investigational agent in the last 30 days

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00296244

Locations

United States, Pennsylvania
Thomas Jefferson University
Philadelphia, Pennsylvania, United States, 19107

Sponsors and Collaborators

Thomas Jefferson University

Novartis Pharmaceuticals

Investigators

Principal Investigator:

Carlo Gerardo B Ramirez, M.D.

Thomas Jefferson University

More Information

No publications provided

Responsible Party:	Thomas Jefferson University
ClinicalTrials.gov Identifier:	NCT00296244 History of Changes
Other Study ID Numbers:	CERL080AUS29
Study First Received:	February 23, 2006
Results First Received:	July 21, 2011
Last Updated:	October 18, 2012
Health Authority:	United States: Food and Drug Administration United States: Institutional Review Board

Keywords provided by Thomas Jefferson University:

steroid-free immunosuppression
liver transplantation

Additional relevant MeSH terms:

Liver Cirrhosis
Fibrosis
Liver Diseases
Digestive System Diseases
Pathologic Processes
Methylprednisolone acetate
Prednisolone acetate
Methylprednisolone
Methylprednisolone Hemisuccinate
Prednisolone
Prednisone
Prednisolone hemisuccinate
Prednisolone phosphate
Mycophenolic Acid
Mycophenolate mofetil

Tacrolimus
Basiliximab
Anti-Inflammatory Agents
Therapeutic Uses
Pharmacologic Actions
Antiemetics
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Central Nervous System Agents
Gastrointestinal Agents
Neuroprotective Agents
Protective Agents
Glucocorticoids
Hormones

ClinicalTrials.gov processed this record on May 23, 2013