Steroid Free Immunosuppression in Liver Transplantation

This study has been completed.
Sponsor:
Collaborator:
Novartis Pharmaceuticals
Information provided by (Responsible Party):
Thomas Jefferson University
ClinicalTrials.gov Identifier:
NCT00296244
First received: February 23, 2006
Last updated: October 18, 2012
Last verified: October 2012
  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:


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

  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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

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
Digestive System Diseases
Liver Diseases
Basiliximab
Methylprednisolone
Methylprednisolone acetate
Methylprednisolone Hemisuccinate
Mycophenolate mofetil
Mycophenolic Acid
Prednisolone
Prednisolone acetate
Prednisolone hemisuccinate
Prednisolone phosphate
Prednisone
Tacrolimus
Anti-Inflammatory Agents
Antibiotics, Antineoplastic
Antiemetics
Antineoplastic Agents
Antineoplastic Agents, Hormonal
Autonomic Agents
Central Nervous System Agents
Enzyme Inhibitors
Gastrointestinal Agents
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Immunologic Factors
Immunosuppressive Agents
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on October 28, 2014