search
Back to results

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

Primary Purpose

End-Stage Renal Disease, Kidney Failure

Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Single-dose rabbit Anti-thymocyte Globulin induction
Divided-dose rabbit Anti-thymocyte Globulin induction
Sponsored by
Wright State University
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for End-Stage Renal Disease focused on measuring Renal transplantation, Kidney transplantation

Eligibility Criteria

18 Years - 65 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • University of Arizona
  • University of Nebraska Medical Center
  • Wake Forest University
  • The Methodist Hospital Research Institute

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

Single-dose Thymoglobulin

Divided-dose Thymoglobulin

Arm Description

Biological/Vaccine Single-dose rabbit Anti-thymocyte Globulin induction, 6 mg/kg IV infusion

Biological/Vaccine Divided-dose rabbit Anti-thymocyte Globulin induction, 1.5 mg/kg IV infusion QD x 4

Outcomes

Primary Outcome Measures

Composite Endpoint of 5 Components: Fever, Hypoxia, Hypotension, Cardiac Events, and Delayed Graft Function
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
Kaplan-Meier estimate of the number of patients who survived for the 12 months after kidney transplantation.
Graft Survival
Kaplan-Meier estimates of graft survival probability for 12 months after transplantation
Acute Kidney Rejection
Kaplan-Meier probability estimates of rejection rates
Incomplete Thymoglobulin Infusion
Kidney Function
Estimated Glomerular Filtration Rate using the abbreviated MDRD formula (Modification of Diet in Renal Disease study)

Full Information

First Posted
May 19, 2009
Last Updated
November 2, 2015
Sponsor
Wright State University
Collaborators
Sanofi, University of Arizona, Wake Forest University, University of Nebraska, The Methodist Hospital Research Institute
search

1. Study Identification

Unique Protocol Identification Number
NCT00906204
Brief Title
Safety Trial of Single Versus Multiple Dose Thymoglobulin Induction in Kidney Transplantation
Acronym
STAT
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
Study Type
Interventional

2. Study Status

Record Verification Date
November 2015
Overall Recruitment Status
Completed
Study Start Date
March 2010 (undefined)
Primary Completion Date
July 2014 (Actual)
Study Completion Date
July 2014 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Wright State University
Collaborators
Sanofi, University of Arizona, Wake Forest University, University of Nebraska, The Methodist Hospital Research Institute

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
End-Stage Renal Disease, Kidney Failure
Keywords
Renal transplantation, Kidney transplantation

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigator
Allocation
Randomized
Enrollment
99 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Single-dose Thymoglobulin
Arm Type
Experimental
Arm Description
Biological/Vaccine Single-dose rabbit Anti-thymocyte Globulin induction, 6 mg/kg IV infusion
Arm Title
Divided-dose Thymoglobulin
Arm Type
Active Comparator
Arm Description
Biological/Vaccine Divided-dose rabbit Anti-thymocyte Globulin induction, 1.5 mg/kg IV infusion QD x 4
Intervention Type
Biological
Intervention Name(s)
Single-dose rabbit Anti-thymocyte Globulin induction
Other Intervention Name(s)
Thymoglobulin, rATG
Intervention Description
6 mg of rATG administered in a single dose on the day of kidney transplantation
Intervention Type
Biological
Intervention Name(s)
Divided-dose rabbit Anti-thymocyte Globulin induction
Other Intervention Name(s)
Thymoglobulin, rATG
Intervention Description
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.
Primary Outcome Measure Information:
Title
Composite Endpoint of 5 Components: Fever, Hypoxia, Hypotension, Cardiac Events, and Delayed Graft Function
Description
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
Time Frame
During first 7 days after kidney transplantation
Secondary Outcome Measure Information:
Title
Patient Survival
Description
Kaplan-Meier estimate of the number of patients who survived for the 12 months after kidney transplantation.
Time Frame
12 months post-transplantation
Title
Graft Survival
Description
Kaplan-Meier estimates of graft survival probability for 12 months after transplantation
Time Frame
12 months post-transplantation
Title
Acute Kidney Rejection
Description
Kaplan-Meier probability estimates of rejection rates
Time Frame
12 months post-transplantation
Title
Incomplete Thymoglobulin Infusion
Time Frame
First 7 days post-transplantation
Title
Kidney Function
Description
Estimated Glomerular Filtration Rate using the abbreviated MDRD formula (Modification of Diet in Renal Disease study)
Time Frame
12 months post-transplantation

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility 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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
R.Brian Stevens, MD, PhD
Organizational Affiliation
Wright State University, Dayton, Ohio
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of Arizona
City
Tucson
State/Province
Arizona
ZIP/Postal Code
85724
Country
United States
Facility Name
University of Nebraska Medical Center
City
Omaha
State/Province
Nebraska
ZIP/Postal Code
68198
Country
United States
Facility Name
Wake Forest University
City
Winston-Salem
State/Province
North Carolina
ZIP/Postal Code
27157
Country
United States
Facility Name
The Methodist Hospital Research Institute
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
18497677
Citation
Stevens RB, Mercer DF, Grant WJ, Freifeld AG, Lane JT, Groggel GC, Rigley TH, Nielsen KJ, Henning ME, Skorupa JY, Skorupa AJ, Christensen KA, Sandoz JP, Kellogg AM, Langnas AN, Wrenshall LE. Randomized trial of single-dose versus divided-dose rabbit anti-thymocyte globulin induction in renal transplantation: an interim report. Transplantation. 2008 May 27;85(10):1391-9. doi: 10.1097/TP.0b013e3181722fad.
Results Reference
background
PubMed Identifier
25083614
Citation
Stevens RB, Foster KW, Miles CD, Lane JT, Kalil AC, Florescu DF, Sandoz JP, Rigley TH, Nielsen KJ, Skorupa JY, Kellogg AM, Malik T, Wrenshall LE. A randomized 2x2 factorial trial, part 1: single-dose rabbit antithymocyte globulin induction may improve renal transplantation outcomes. Transplantation. 2015 Jan;99(1):197-209. doi: 10.1097/TP.0000000000000250.
Results Reference
background
PubMed Identifier
26696251
Citation
Stevens RB, Wrenshall LE, Miles CD, Farney AC, Jie T, Sandoz JP, Rigley TH, Osama Gaber A. A Double-Blind, Double-Dummy, Flexible-Design Randomized Multicenter Trial: Early Safety of Single- Versus Divided-Dose Rabbit Anti-Thymocyte Globulin Induction in Renal Transplantation. Am J Transplant. 2016 Jun;16(6):1858-67. doi: 10.1111/ajt.13659. Epub 2016 Mar 7.
Results Reference
derived

Learn more about this trial

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

We'll reach out to this number within 24 hrs