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

November 2, 2015 updated by: R. Brian Stevens, MD, PhD, FACS, FAST, Wright State University

Prospective, Randomized, Double-Blind, Double-Dummy, Multicenter Trial to Assess Safety of Single Dose vs. Traditional Administration of Thymoglobulin Induction for Renal Transplantation

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

99

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Arizona
      • Tucson, Arizona, United States, 85724
        • University of Arizona
    • Nebraska
      • Omaha, Nebraska, United States, 68198
        • University of Nebraska Medical Center
    • North Carolina
      • Winston-Salem, North Carolina, United States, 27157
        • Wake Forest University
    • Texas
      • Houston, Texas, United States, 77030
        • The Methodist Hospital Research Institute

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 65 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Triple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Composite Endpoint of 5 Components: Fever, Hypoxia, Hypotension, Cardiac Events, and Delayed Graft Function
Time Frame: During first 7 days after kidney transplantation

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
During first 7 days after kidney transplantation

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Patient Survival
Time Frame: 12 months post-transplantation
Kaplan-Meier estimate of the number of patients who survived for the 12 months after kidney transplantation.
12 months post-transplantation
Graft Survival
Time Frame: 12 months post-transplantation
Kaplan-Meier estimates of graft survival probability for 12 months after transplantation
12 months post-transplantation
Acute Kidney Rejection
Time Frame: 12 months post-transplantation
Kaplan-Meier probability estimates of rejection rates
12 months post-transplantation
Incomplete Thymoglobulin Infusion
Time Frame: First 7 days post-transplantation
First 7 days post-transplantation
Kidney Function
Time Frame: 12 months post-transplantation
Estimated Glomerular Filtration Rate using the abbreviated MDRD formula (Modification of Diet in Renal Disease study)
12 months post-transplantation

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Wright State University

Collaborators

Sanofi
University of Nebraska
University of Arizona
The Methodist Hospital Research Institute
Wake Forest University

Investigators

  • Principal Investigator: R.Brian Stevens, MD, PhD, Wright State University, Dayton, Ohio

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

March 1, 2010

Primary Completion (Actual)

July 1, 2014

Study Completion (Actual)

July 1, 2014

Study Registration Dates

First Submitted

May 19, 2009

First Submitted That Met QC Criteria

May 20, 2009

First Posted (Estimate)

May 21, 2009

Study Record Updates

Last Update Posted (Estimate)

December 7, 2015

Last Update Submitted That Met QC Criteria

November 2, 2015

Last Verified

November 1, 2015

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 183-09-FB

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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