Evaluation of Thymoglobulin Induction and Reduced Doses of Calcineurin Inhibitors on Liver Transplant Rejection - Full Text View

Purpose

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	Intervention	Phase
Liver Dysfunction Rejection, Transplant Transplantation, Liver	Biological: Thymoglobulin Drug: Corticosteroid Drug: Tacrolimus Drug: Mycophenolate Mofetil	Phase 2


Study Type:	Interventional
Study Design:	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

Resource links provided by NLM:

MedlinePlus related topics: Liver Transplantation

U.S. FDA Resources

Further study details as provided by Sanofi ( Genzyme, a Sanofi Company ):

Primary Outcome Measures:

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

Secondary Outcome Measures:

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


Enrollment:	75
Study Start Date:	April 2005
Study Completion Date:	December 2007
Primary Completion Date:	December 2007 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: 1 Standard (tacrolimus based standard therapy without induction)	Biological: Thymoglobulin Antibody inductions with tacrolimus and corticosteroid sparing maintenance therapy Other Name: [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

Eligibility


Ages Eligible for Study:	18 Years and older (Adult, Senior)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

Criteria

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

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: NCT00117689

Locations


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

Sponsors and Collaborators

Genzyme, a Sanofi Company

Investigators


Study Director:	Medical Monitor	Genzyme, a Sanofi Company

More Information


Responsible Party:	Genzyme, a Sanofi Company
ClinicalTrials.gov Identifier:	NCT00117689 History of Changes
Other Study ID Numbers:	Thymo102700103
Study First Received:	June 30, 2005
Last Updated:	March 17, 2015

Keywords provided by Sanofi ( Genzyme, a Sanofi Company ):


Anti-T cell antibodies Primary Liver Transplantation and Renal Dysfunction Liver Transplant Rejection Induction Therapy with reduction of Calcineurin inhibitors	Primary Liver Transplantation Primary Transplant Rejection Transplantation, Liver Rejection, Transplant

Additional relevant MeSH terms:


Liver Diseases Digestive System Diseases Tacrolimus Mycophenolate mofetil Antilymphocyte Serum Calcineurin Inhibitors Mycophenolic Acid	Immunosuppressive Agents Immunologic Factors Physiological Effects of Drugs Enzyme Inhibitors Molecular Mechanisms of Pharmacological Action Antibiotics, Antineoplastic Antineoplastic Agents

ClinicalTrials.gov processed this record on September 21, 2017