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Safety Trial of Single Versus Multiple Dose Thymoglobulin Induction in Kidney Transplantation (STAT)

This study is currently recruiting participants.
Verified February 2013 by Wright State University
Sponsor:
Collaborators:
Sanofi
University of Arizona
Wake Forest University
University of Nebraska
Methodist Hospital Research Institute, Houston, Texas
Information provided by (Responsible Party):
R. Brian Stevens, MD, PhD, FACS, Wright State University
ClinicalTrials.gov Identifier:
NCT00906204
First received: May 19, 2009
Last updated: February 12, 2013
Last verified: February 2013
History of Changes
  Purpose

In a non-blinded pilot study conducted at the University of Nebraska Medical Center, evidence was found that a single large dose of Thymoglobulin on the day of kidney transplantation produced better kidney function than the standard dosing plan, when the same amount is divided into smaller doses on 4 days. This new study repeats that dose comparison, but with double-blinding and at multiple transplantation centers.


Condition Intervention Phase
End-Stage Renal Disease
Kidney Failure
Kidney Transplantation
 Drug: Anti-thymocyte Globulin (rabbit) (rATG) (Thymoglobulin)
Drug: Divided-dose Thymoglobulin administration
 Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Treatment
Official Title: Prospective, Randomized, Double-Blind, Double-Dummy, Multicenter Trial to Assess Safety of Single Dose vs. Traditional Administration of Thymoglobulin Induction for Renal Transplantation

Resource links provided by NLM:

U.S. FDA Resources

Further study details as provided by Wright State University:

Primary Outcome Measures:
  • Composite endpoint of 5 components: Fever, Hypoxia, Hypotension, Cardiac Events, and Delayed Graft Function [ Time Frame: During first 7 days after kidney transplantation ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Patient Survival [ Time Frame: 12 months post-transplantation ] [ Designated as safety issue: Yes ]
  • Graft survival [ Time Frame: 12 months post-transplantation ] [ Designated as safety issue: Yes ]
  • Acute rejection of transplanted kidney; biopsy-confirmed, clinically symptomatic [ Time Frame: 12 months post-transplantation ] [ Designated as safety issue: Yes ]
  • Incomplete Thymoglobulin infusion [ Time Frame: First 7 days post-transplantation ] [ Designated as safety issue: Yes ]
  • Short-term kidney function (Immediately after transplantation) [ Time Frame: Post-transplantation days 1-4 ] [ Designated as safety issue: No ]
  • Longer-term kidney function [ Time Frame: Post-transplantation months 3 - 12 ] [ Designated as safety issue: No ]
  • Hematologic effects of Thymoglobulin administration (Effects of the 2 different dosing plans on white and red blood cells and platelets) [ Time Frame: 12 months post-transplantation ] [ Designated as safety issue: Yes ]
  • Immunologic effects of Thymoglobulin administration (studies of antibodies and specific immune cell types in the blood after transplantation) [ Time Frame: 12 months post-transplantation ] [ Designated as safety issue: No ]
  • Histopathology of kidney biopsies taken at transplantation and after 12 months [ Time Frame: 12 months post-transplantation ] [ Designated as safety issue: No ]

Estimated Enrollment: 165
Study Start Date: March 2010
Estimated Study Completion Date: March 2015
Estimated Primary Completion Date: March 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Single-dose Thymoglobulin
Patients will receive 6 mg of Thymoglobulin per kilogram of body weight, all on the day of kidney transplantation
 Drug: Anti-thymocyte Globulin (rabbit) (rATG) (Thymoglobulin)
6 mg of rATG administered in a single dose on the day of kidney transplantation
Active Comparator: Divided-dose Thymoglobulin
Patients will receive 6 mg of Thymoglobulin per kilogram of body weight, divided into 4 equal 1.5 mg/Kg doses, administered on 4 sequential days beginning on the day of kidney transplantation.
 Drug: Divided-dose Thymoglobulin administration
6 mg/Kg total Thymoglobulin dose administered as 1.5 mg/Kg doses on 4 sequential days, beginning on the day of kidney transplantation.

Detailed Description:

Two randomized groups of kidney transplant recipients will be each administered the drug Thymoglobulin according to a different dosing regimen. The control group will receive the usual and traditional regimen of a total of 6 mg/Kg divided into 4 doses, 1 on the day of transplantation and 1 each day on the next 3 days. The experimental group will receive the same total Thymoglobulin dose, 6 mg/Kg, but entirely on the day of transplantation.

The study will be double-blinded, with placebo doses of Thymoglobulin administered as needed to enrollees in the experimental group. Enrollment is targeted at 165, with 150 subjects needed to complete the study for adequate evaluation.

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Subject capable of giving written informed consent, with end-stage kidney disease, who is a suitable candidate for primary kidney transplantation
  • Male or female subject who has reached legal age in the state where they reside and is at least 18 years of age
  • Deceased or living donors
  • Compatible ABO blood type
  • Expanded-criteria donor (ECD) kidneys with a donor grade score of ≤ 25 (as developed by Nyberg, et al.)
  • If Kidneys are pumped, they must meet the following pumping parameters: resistance <0.35 with a flow rate of >60 ml/min.

Exclusion Criteria:

  • Recipient age >65 years
  • PRA >50%, or donor-specific antibody
  • CIT >30 hours
  • Re-transplant patients
  • Multi-organ transplant recipients (example: kidney/pancreas or kidney/liver)
  • Renal transplant recipients planned for future pancreas transplantation
  • Current unstable cardiovascular disease or history of myocardial infarction within the previous 6 months
  • Current malignancy or history or malignancy (within the previous 5 years) with the exception of non-metastatic basal or squamous cell carcinoma of the skin or carcinoma in-situ of the cervix that has been treated successfully.
  • Hepatitis B and C recipients or active liver disease
  • HIV positive recipients
  • Primary disease requiring treatment with steroids after transplantation
  • Expanded-criteria donor kidneys (current UNOS criteria) with a donor grade score of > 25
  • Donation after cardiac death (DCD) donors
  • Dual adult kidneys
  • Recipients of pediatric (age <12 years) unilateral or en-bloc kidneys
  • Previous treatment with rATG
  • Known hypersensitivity, extensive exposure, or allergy to rabbits
  • Pregnant
  • Any condition that in the investigator's opinion may compromise study participation (e.g., history or likelihood of non-compliance with immunosuppression regimen, protocol visits, tests, and studies)

Relative Exclusion Criteria:

  • Patients with a BMI > 37 should be considered on an individual basis based on overall health and body habitus.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00906204

Contacts
Contact: R. Brian Stevens, MD, PhD 937-208-4735 rbstevens@mvh.org
Contact: Theodore Rigley, CTBS 937-208-3842 thrigley@mvh.org

Locations
United States, Arizona
University of Arizona Completed
Tucson, Arizona, United States, 85724
United States, Nebraska
University of Nebraska Medical Center Completed
Omaha, Nebraska, United States, 68198
United States, North Carolina
Wake Forest University Completed
Winston-Salem, North Carolina, United States, 27157
United States, Texas
The Methodist Hospital Research Institute Recruiting
Houston, Texas, United States, 77030
Contact: Osama Gaber, MD     713-441-6174     aogaber@tmhs.org    
Principal Investigator: Osama Gaber, MD            
Sponsors and Collaborators
Wright State University
Sanofi
University of Arizona
Wake Forest University
University of Nebraska
Methodist Hospital Research Institute, Houston, Texas
Investigators
Principal Investigator: R.Brian Stevens, MD, PhD University of Nebraska
  More Information

Publications:

Responsible Party: R. Brian Stevens, MD, PhD, FACS, Professor of Surgery and Graduate Studies and Director, Transplantation Division, Wright State University
ClinicalTrials.gov Identifier: NCT00906204     History of Changes
Other Study ID Numbers: 183-09-FB
Study First Received: May 19, 2009
Last Updated: February 12, 2013
Health Authority: United States: Institutional Review Board

Keywords provided by Wright State University:
Renal transplantation
Kidney transplantation

Additional relevant MeSH terms:
Kidney Diseases
Kidney Failure, Chronic
Renal Insufficiency
Urologic Diseases
Renal Insufficiency, Chronic
 Antilymphocyte Serum
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on May 16, 2013