Safety and Efficacy Study of Thymoglobulin Versus IL2 Receptor Antagonists

End Stage Renal Disease Clinical Trial

Official title:

Rabbit Anti-thymocyte Globulin Versus IL2 Receptor Antagonists in Combination With Tacrolimus, Corticosteroids and Mycophenolate Mofetil in a Predominantly High Risk Kidney Transplant Population.

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT00859131
• Other study ID #: thymo vs IL2
• Status: Active, not recruiting
• Phase: N/A
• First received: March 6, 2009
• Last updated: February 28, 2014
• Start date: March 2009
• Est. completion date: July 2014

Study information

• Verified date: February 2014
• Source: Medical University of South Carolina
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to evaluate the safety and efficacy of induction therapy with Thymoglobulin in comparison with IL2 receptor antagonists (daclizumab or basiliximab).

Description:

A 12 month, prospective, randomized, single center, open-label study to evaluate the safety and efficacy of Rabbit anti-thymocyte globulin versus IL2 receptor antagonists in combination with tacrolimus, corticosteroids and mycophenolate mofetil in a predominantly high risk kidney transplant population.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 200
• Est. completion date: July 2014
• Est. primary completion date: July 2012
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 75 Years

Eligibility

Inclusion Criteria:

• Male and female patients between 18 and 75 years of age

• Male or female patients who are primary or repeat cadaveric, living unrelated or non- Human leukocyte antigen (HLA) identical living related donor renal transplant recipients

• Female patients of child bearing potential must have a negative urine or serum pregnancy test within the past 48 hours prior to study inclusion.

• The patient has given written informed consent to participate in the study

Exclusion Criteria:

• Patient has previously received or is receiving an organ transplant other than a kidney.

• Patients who are recipients of a multiple organ transplant.

• Patient has received a primary or re-transplant from an HLA-identical living donor.

• Any positive cross-match.

• Patient is the recipient of a pediatric donor kidney from a pediatric donor aged 8 years or less.

• Patient has received an ABO incompatible donor kidney.

• Recipient or donor is known to be seropositive for hepatitis C virus (HCV) or B virus (HBV) except for hepatitis B surface antibody positive.

• Recipient or donor is known to be seropositive for human immunodeficiency virus (HIV).

• Patient has uncontrolled concomitant infection or any other unstable medical condition that could interfere with the study objectives.

• Patients with thrombocytopenia (<75,000/mm3 ), with an absolute neutrophil count of < 1,000/mm3); and/or leucopoenia (< 2,000/mm3), or anemia (hemoglobin < 6 g/dL) prior to study inclusion.

• Patient is taking or has been taking an investigational drug in the 30 days prior to transplant.

• Patient has a known hypersensitivity to tacrolimus, mycophenolate mofetil, rabbit anti-thymocyte globulin, daclizumab or corticosteroids.

• Patients with severe diarrhea or other gastrointestinal disorders that might interfere with their ability to absorb oral medication.

• Patients with a history of malignancy within the last five years, except for successfully excised squamous or basal cell carcinoma of the skin.

• Patient is pregnant or lactating, where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by positive human Chorionic Gonadotropin (hCG) laboratory test.

• Women of childbearing potential must use two reliable forms of contraception simultaneously, unless they are status post bilateral tubal ligation, bilateral oophorectomy, or hysterectomy. Effective contraception must be used before beginning study drug therapy, for the duration of the study and for 6 weeks following completion of the study.

• Patient has any form of substance abuse, psychiatric disorder or a condition that, in the opinion of the investigator, may invalidate communication with the investigator.

• Inability to cooperate or communicate with the investigator.

Study Design

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

Related Conditions & MeSH terms

• End Stage Renal Disease
• Kidney Failure, Chronic

Intervention

Drug:
• Rabbit Antithymocyte globulin
1.5 mg/kg IV pre-op, day 1, day 2, day 3, day 4
• Daclizumab
1.0 mg/kg pre-op and 1.0 mg/kg on Day 7

Locations

Country	Name	City	State
United States	Medical University of South Carolina	Charleston	South Carolina

Sponsors (2)

Lead Sponsor	Collaborator
Medical University of South Carolina	Genzyme, a Sanofi Company

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Treatment efficacy will be defined as the incidence of all biopsy proven acute rejection and calculated creatinine clearance using the abbreviated MDRD equation at one year post-transplant.		One year	No
Secondary	Evaluate the safety and tolerability of rabbit anti-thymocyte globulin or daclizumab or basiliximab in combination with tacrolimus, corticosteroids and mycophenolate mofetil.		One year	Yes
Secondary	Proportion of patients requiring antilymphocyte therapy for acute rejection.		One year	No
Secondary	Patient and graft survival at one year post-transplant		One year	No
Secondary	Incidence of post-transplant diabetes mellitus (PTDM), defined as post-discharge new need for insulin or oral hypoglycemic agents and meeting current ADA diagnostic criteria for diabetes mellitus		One year	No
Secondary	Incidence of post-transplant infections, including, but not limited to, CMV infection and disease, BK infection and nephropathy, other opportunistic infections, urinary tract infections, pneumonia, and sepsis		one year	Yes
Secondary	Patient weight change		one year	No
Secondary	Incidence and severity of hypercholesterolemia (total cholesterol, HDL cholesterol, LDL cholesterol) and hypertriglyceridemia and treatment of hyperlipidemia, as defined in NCEP III guidelines		One year	No
Secondary	Incidence of post-transplant malignancies, including post-transplant lymphoproliferative disease (PTLD) and skin cancers.		One year	Yes
Secondary	Incidence of leukopenia, defined as a total white blood cell count of less than 2,000 cells/mm3 and neutropenia, defined as an absolute neutrophil count of less than 1,000 cells/mm3 and need for colony stimulating factors		One year	Yes
Secondary	Incidence of thrombocytopenia, defined as a platelet count of less than 100,000 cells/mm3		One year	Yes
Secondary	Incidence of anemia, defined as a hemoglobin of less than 10 g/dL and need for erythropoietin or similar agents		One year	Yes
Secondary	Determine the impact of genotyping using microarray analysis on clinical outcomes and histologic findings		One year	No
Secondary	Utilizing the EuroQoL survey, determine if there is a correlation between graft function and quality of life		One year	No