A Study of Thymoglobulin and Tacrolimus in Liver Transplant (thymo)

• ClinicalTrials.gov Identifier: NCT00564538
• Recruitment Status: Unknown
• First Posted: November 28, 2007
• Last Update Posted: November 28, 2007
• Sponsor: University of Nebraska
• Collaborator: Genzyme, a Sanofi Company
• Information provided by: University of Nebraska

Study Description

Brief Summary:

The purpose of this study is to compare kidney function, long term patient and graft survival, and incidence of acute rejection in liver transplant recipients between one group receiving thymoglobulin induction and delayed initiation of tacrolimus and another group of liver transplant recipients having immediate administration of tacrolimus without any induction immunosuppression.

Condition or disease	Intervention/treatment	Phase
Liver Transplantation; Liver Disease; Immunosuppression	Drug: anti-thymocyte globulin (rabbit); Drug: tacrolimus	Phase 4

Detailed Description:

Renal insufficiency following liver transplantation in adult recipients is a major cause of morbidity and a major contributor to mortality. One of the key factors contributing to this renal dysfunction is the use of calcineurin inhibitors. There is some evidence to suggest that the first 7-10 days following liver transplantation are crucial in terms of renal function and the ability to avoid the use of nephrotoxic agents such as calcineurin inhibitors may have a significant impact on long-term outcome.

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 100 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Study Comparing Thymoglobulin to Tacrolimus in Liver Transplant and Impact on Renal Function
• Study Start Date: December 2007
• Estimated Study Completion Date: December 2009

Arms and Interventions

Arm	Intervention/treatment
Experimental: 1; Patients in arm 1 will receive induction with thymoglobulin at time of transplant with delayed initiation of tacrolimus	Drug: anti-thymocyte globulin (rabbit); 1.5mg/kg per dose with the first dose initiated in the operating room prior to reperfusion of the transplanted liver. It will then be administered again on post operative day #1, 3 and 5 for a total cumulative dose of 6mg/kg.; Other Name: thymoglobulin
Active Comparator: 2; patients in arm 2 will not receive thymo induction at time of transplant and will have immediate initiation of tacrolimus	Drug: tacrolimus; Tacrolimus will be administered orally on post op day #1 as per standard of care.; Other Name: prograf

Outcome Measures

Primary Outcome Measures :

1. Evaluation of renal function via Glo-Fil nuclear medicine scan and laboratory parameters [ Time Frame: Post operative day #1, month 6 and month 12 ]

Secondary Outcome Measures :

1. patient and graft survival, incidence of acute rejection, incidence of active CMV disease, incidence of other infections, any adverse events or serious adverse events associated with the use of thymo induction therapy [ Time Frame: post op days 1-6, months 3,6, 9, and 12 ]

Eligibility Criteria

• Ages Eligible for Study: 19 Years and older (Adult, Older Adult)
• 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
• Over 18 years of age
• Signed informed consent form
• if female of childbearing potential: Must not be lactating Must have negative serum pregnancy test on study day 0 Must have agreed on a reliable and acceptable form of contraception during the study
• sexually active males must be practicing an acceptable form of contraception

Exclusion Criteria:

• Multiple organ transplants
• Prior solid organ or bone marrow transplant recipients
• Fulminant hepatic failure
• Status 1 transplants
• Liver transplant candidates with greater than 6 weeks of dialysis
• Patients who in the opinion of the Investigator are not eligible for thymo induction at the time of transplant
• Recipients of investigational therapy within 90 days prior to transplant
• Know contraindication to administration of rabbit anti-thymocyte globulin
• Patients whose medical condition is such that the physician feels it would not be in their best interest to participate in the study
• Patients who are unwilling to have a Glofil nuclear medicine scan at specified time points
• 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

Contacts and Locations

Locations

United States, Nebraska

University of Nebraska Medical Center

Omaha, Nebraska, United States, 68198

Sponsors and Collaborators

University of Nebraska

Genzyme, a Sanofi Company

Investigators

• Principal Investigator: Wendy Grant, MD; University of Nebraska

More Information

Publications:

1. Fisher NC, Nightingale PG, Gunson BK, Lipkin GW, JM. N. Chronic renal failure following liver transplantation: a retrospective analysis Transplantation 1998; 66 (1): 59. 2. Gonwa TA, Mai ML, Melton LB, et al. End-stage renal disease (ESRD) after orthotopic lvier transplantation (OLTX) using calcineurin-based immunotherapy. Transplantation 2001; 72: 1934. 3. Moreno JM, Cuervas-Mons V, Rubio E, et al. Chronic renal dysfunction after liver transplantation in adult patients: prevelance, risk factors, and impact on mortality. Transplant Proc 2003; 35 (5): 1907.

• ClinicalTrials.gov Identifier: NCT00564538
• Other Study ID Numbers: 424-07
• First Posted: November 28, 2007
• Last Update Posted: November 28, 2007
• Last Verified: November 2007

Keywords provided by University of Nebraska:

liver transplant

Additional relevant MeSH terms:

Liver Diseases; Digestive System Diseases; Tacrolimus; Thymoglobulin; Antilymphocyte Serum; Immunosuppressive Agents; Immunologic Factors; Physiological Effects of Drugs; Calcineurin Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action