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

This study has been completed.
Sponsor:
Collaborators:
Sanofi
University of Arizona
Wake Forest University
University of Nebraska
The Methodist Hospital System
Information provided by (Responsible Party):
R. Brian Stevens, MD, PhD, FACS, FAST, Wright State University
ClinicalTrials.gov Identifier:
NCT00906204
First received: May 19, 2009
Last updated: November 2, 2015
Last verified: November 2015
  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
Biological: Single-dose rabbit Anti-thymocyte Globulin induction
Biological: Divided-dose rabbit Anti-thymocyte Globulin induction
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:


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 ]

    The composite endpoint components and definitions are:

    • Fever: Body temperature ≥ 38.5˚C.
    • Hypotension: After rATG initiation, systolic blood pressure ≤ 90 mmHg requiring de novo treatment with vasopressors.
    • Hypoxia: During transplantation surgery, increase in FiO2 to ≥ 60% following rATG initiation. Following transplantation, starting in recovery room, FiO2 ≥ 50% or nasal cannula delivering ≥ 3 liters, either singly or combined, for > 12 hours out of a 24 hour period.
    • Cardiac events: Myocardial Infarction, clinically significant dysrhythmia (atrial fibrillation, atrial flutter, ventricular fibrillation and ventricular tachycardia)
    • Delayed graft function (DGF): Requirement for dialysis within 7 days of transplantation


Secondary Outcome Measures:
  • Patient Survival [ Time Frame: 12 months post-transplantation ] [ Designated as safety issue: Yes ]
    Kaplan-Meier estimate of the number of patients who survived for the 12 months after kidney transplantation.

  • Graft Survival [ Time Frame: 12 months post-transplantation ] [ Designated as safety issue: Yes ]
    Kaplan-Meier estimates of graft survival probability for 12 months after transplantation

  • Acute Kidney Rejection [ Time Frame: 12 months post-transplantation ] [ Designated as safety issue: Yes ]
    Kaplan-Meier probability estimates of rejection rates

  • Incomplete Thymoglobulin Infusion [ Time Frame: First 7 days post-transplantation ] [ Designated as safety issue: Yes ]
  • Kidney Function [ Time Frame: 12 months post-transplantation ] [ Designated as safety issue: No ]
    Estimated Glomerular Filtration Rate using the abbreviated MDRD formula (Modification of Diet in Renal Disease study)


Enrollment: 99
Study Start Date: March 2010
Study Completion Date: July 2014
Primary Completion Date: July 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Single-dose Thymoglobulin
Biological/Vaccine Single-dose rabbit Anti-thymocyte Globulin induction, 6 mg/kg IV infusion
Biological: Single-dose rabbit Anti-thymocyte Globulin induction
6 mg of rATG administered in a single dose on the day of kidney transplantation
Other Names:
  • Thymoglobulin
  • rATG
Active Comparator: Divided-dose Thymoglobulin
Biological/Vaccine Divided-dose rabbit Anti-thymocyte Globulin induction, 1.5 mg/kg IV infusion QD x 4
Biological: Divided-dose rabbit Anti-thymocyte Globulin induction
6 mg/kg total rabbit Anti-thymocyte Globulin dose administered as 1.5 mg/kg doses on 4 sequential days, beginning on the day of kidney transplantation.
Other Names:
  • Thymoglobulin
  • rATG

Detailed Description:

This study is designed to confirm the one-year safety of single-dose rabbit anti-thymocyte globulin induction at kidney transplantation, compared to the conventional administration of the same overall dose divided into four smaller doses across four days. 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
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: NCT00906204

Locations
United States, Arizona
University of Arizona
Tucson, Arizona, United States, 85724
United States, Nebraska
University of Nebraska Medical Center
Omaha, Nebraska, United States, 68198
United States, North Carolina
Wake Forest University
Winston-Salem, North Carolina, United States, 27157
United States, Texas
The Methodist Hospital Research Institute
Houston, Texas, United States, 77030
Sponsors and Collaborators
Wright State University
Sanofi
University of Arizona
Wake Forest University
University of Nebraska
The Methodist Hospital System
Investigators
Principal Investigator: R.Brian Stevens, MD, PhD Wright State University, Dayton, Ohio
  More Information

Publications:
Responsible Party: R. Brian Stevens, MD, PhD, FACS, FAST, 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
Results First Received: September 11, 2015
Last Updated: November 2, 2015
Health Authority: United States: Institutional Review Board

Keywords provided by Wright State University:
Renal transplantation
Kidney transplantation

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

ClinicalTrials.gov processed this record on February 09, 2016