Evaluation of Thymoglobulin Induction and Reduced Doses of Calcineurin Inhibitors on Liver Transplant Rejection

Sponsor

Genzyme, a Sanofi Company (Industry)

Overall Status

Completed

CT.gov ID

NCT00117689

Collaborator

(none)

Enrollment

Locations

Arms

Duration (Months)

4.7

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This study involves the use of a drug called Thymoglobulin, which is approved in the US to treat kidney transplant rejection and in Canada to treat and prevent kidney transplant rejection. This study will evaluate the effect of Thymoglobulin induction therapy and reduced doses of calcineurin inhibitors on the incidence of liver rejection and will provide a basis for future evaluations of Thymoglobulin as an immunosuppressive agent to help decrease the incidence of liver transplant rejection. Subjects meeting all inclusion and exclusion criteria are eligible to participate in this study. Approximately 75 study subjects from up to 18 transplant centers in the United States and Canada will be enrolled in this 12-month study.

Condition or Disease	Intervention/Treatment	Phase
Liver Dysfunction Rejection, Transplant Transplantation, Liver	Biological: Thymoglobulin Drug: Corticosteroid Drug: Tacrolimus Drug: Mycophenolate Mofetil	Phase 2

Study Design

Study Type:

Interventional

Actual Enrollment :

75 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Prevention

Official Title:

A Randomized, Controlled, Multi-Center Study of Thymoglobulin Induction Therapy With a Calcineurin Inhibitor Sparing Regimen in Liver Transplant Patients

Study Start Date :

Apr 1, 2005

Actual Primary Completion Date :

Dec 1, 2007

Actual Study Completion Date :

Dec 1, 2007

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 1 Standard (tacrolimus based standard therapy without induction)	Biological: Thymoglobulin Antibody inductions with tacrolimus and corticosteroid sparing maintenance therapy Other Names: [Anti-thymocyte Globulin (rabbit)] Drug: Tacrolimus Between Day 3 the last dose of Thymoglobulin Drug: Mycophenolate Mofetil for at least 1 month posttransplant
Active Comparator: 2 Standard of Care Thymoglobulin with tacrolimus and corticosteroid sparing maintenance therapy	Drug: Corticosteroid For a minimum of 3 months Drug: Tacrolimus Between Day 3 the last dose of Thymoglobulin Drug: Mycophenolate Mofetil for at least 1 month posttransplant

Arm

Intervention/Treatment

Experimental: 1

Standard (tacrolimus based standard therapy without induction)

Biological: Thymoglobulin

Antibody inductions with tacrolimus and corticosteroid sparing maintenance therapy

Other Names:

[Anti-thymocyte Globulin (rabbit)]

Drug: Tacrolimus

Between Day 3 the last dose of Thymoglobulin

Drug: Mycophenolate Mofetil

for at least 1 month posttransplant

Active Comparator: 2 Standard of Care

Thymoglobulin with tacrolimus and corticosteroid sparing maintenance therapy

Drug: Corticosteroid

For a minimum of 3 months

Drug: Tacrolimus

Between Day 3 the last dose of Thymoglobulin

Drug: Mycophenolate Mofetil

for at least 1 month posttransplant

Outcome Measures

Primary Outcome Measures

Freedom from biopsy-proven acute rejection (including humoral rejection) [6 months]

Secondary Outcome Measures

Explore the impact of Thymoglobulin on kidney function after transplant [6 months]
Explore the impact of Thymoglobulin on the prevention of liver transplant rejection, transplanted liver loss, death, and safety of Thymoglobulin after transplant. [12 months]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Primary liver transplant recipient with Model for End-Stage Liver Disease (MELD) criteria documentation
Serum creatinine > 1.5mg/dL at the time of transplant, or based on the value used to calculate the most recent pre-operative MELD Score for liver allocation
Ages greater than or equal to 18 years
If female, must not be lactating; must have a negative serum beta-human chorionic gonadotropin (HCG) test within 7 days prior to Study Day 0 (Day of Transplant); and must agree to practice an acceptable and reliable form of contraception during the study
Signed informed consent

Exclusion Criteria:

Living donor or multiple organ transplants
Prior solid organ or bone marrow transplant recipient
Fulminant hepatic failure
Status 1 transplants
ABO incompatible transplants
Transplants utilizing livers from non heart-beating donors
Liver transplant candidates with > 6 weeks of analysis
Donor with positive serology for hepatitis B surface antigen (HBsAg)
Evidence of human immunodeficiency virus (HIV)
Autoimmune hepatitis
History of chronic steroid or immunosuppressant use in the 90 days prior to transplant, except for inhaled corticosteroids to treat asthma
Recipient of investigational therapy within 90 days prior to transplant procedure
Known contraindication to administration of rabbit anti-thymocyte globulin
Acute viral illness
History of malignancy within 5 years, with the exception of adequately treated localized squamous or basal cell carcinoma of the skin without evidence of recurrence, and/or hepatocellular carcinoma
Illness other than primary liver disease (e.g. severe ischemic heart disease, left ventricular dysfunction, or pulmonary disease), which, in the opinion of the investigator, may significantly increase the risk of the transplantation procedure
Current drug and alcohol abuse that, in the opinion of the investigator, puts subjects at risk for poor compliance (no drug test required)

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Alabama, Birmingham	Birmingham	Alabama	United States	35294
2	USC University Hospital	Los Angeles	California	United States	90033
3	University of California, San Fransisco Hospital	San Francisco	California	United States	94143
4	University of Colorado Hospital and Health Sciences Center	Denver	Colorado	United States	80262
5	Mayo Clinic Jacksonville	Jacksonville	Florida	United States	32224
6	University of Miami	Miami	Florida	United States	33136
7	Fairview University Medical Center	Minneapolis	Minnesota	United States	55455
8	Washington University Medical Center	St. Louis	Missouri	United States	63110
9	University of Nebraska	Omaha	Nebraska	United States	68198
10	Mount Sinai Medical Center	New York	New York	United States	10029
11	University of Cincinnati Medical Center	Cincinnati	Ohio	United States	45267
12	Baylor University Medical Center	Dallas	Texas	United States	75246
13	University of Texas Health Science Center at San Antonio, University Hospital	San Antonio	Texas	United States	78229
14	VCU Medical Center	Richmond	Virginia	United States	23298
15	Toronto University Hospital - UHN	Toronto	Ontario	Canada	M5G 2N2
16	Royal Victoria Hospital	Montreal	Quebec	Canada	H3A 1A1