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

Liver Dysfunction Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00117689
• Other study ID #: Thymo102700103
• Status: Completed
• Phase: Phase 2
• First received: June 30, 2005
• Last updated: March 17, 2015
• Start date: April 2005
• Est. completion date: December 2007

Study information

• Verified date: March 2015
• Source: Sanofi
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 75
• Est. completion date: December 2007
• Est. primary completion date: December 2007
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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)

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Prevention

Related Conditions & MeSH terms

• Liver Dysfunction
• Rejection, Transplant
• Transplantation, Liver

Intervention

Biological:
• Thymoglobulin
Antibody inductions with tacrolimus and corticosteroid sparing maintenance therapy

Drug:
• Corticosteroid
For a minimum of 3 months
• Tacrolimus
Between Day 3 the last dose of Thymoglobulin
• Mycophenolate Mofetil
for at least 1 month posttransplant

Locations

Country	Name	City	State
Canada	Royal Victoria Hospital	Montreal	Quebec
Canada	Toronto University Hospital - UHN	Toronto	Ontario
United States	University of Alabama, Birmingham	Birmingham	Alabama
United States	University of Cincinnati Medical Center	Cincinnati	Ohio
United States	Baylor University Medical Center	Dallas	Texas
United States	University of Colorado Hospital and Health Sciences Center	Denver	Colorado
United States	Mayo Clinic Jacksonville	Jacksonville	Florida
United States	USC University Hospital	Los Angeles	California
United States	University of Miami	Miami	Florida
United States	Fairview University Medical Center	Minneapolis	Minnesota
United States	Mount Sinai Medical Center	New York	New York
United States	University of Nebraska	Omaha	Nebraska
United States	VCU Medical Center	Richmond	Virginia
United States	University of Texas Health Science Center at San Antonio, University Hospital	San Antonio	Texas
United States	University of California, San Fransisco Hospital	San Francisco	California
United States	Washington University Medical Center	St. Louis	Missouri

Sponsors (1)

Lead Sponsor	Collaborator
Genzyme, a Sanofi Company

Countries where clinical trial is conducted

United States,  Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Freedom from biopsy-proven acute rejection (including humoral rejection)		6 months	Yes
Secondary	Explore the impact of Thymoglobulin on kidney function after transplant		6 months	Yes
Secondary	Explore the impact of Thymoglobulin on the prevention of liver transplant rejection, transplanted liver loss, death, and safety of Thymoglobulin after transplant.		12 months	Yes

External Links

•   US FDA Approved Full Prescribing Information for Thymoglobulin®