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

End-Stage Renal Disease Clinical Trial

— 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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00906204
• Other study ID #: 183-09-FB
• Status: Completed
• Phase: Phase 2
• First received: May 19, 2009
• Last updated: November 2, 2015
• Start date: March 2010
• Est. completion date: July 2014

Study information

• Verified date: November 2015
• Source: Wright State University
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 99
• Est. completion date: July 2014
• Est. primary completion date: July 2014
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 65 Years

Eligibility

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 Design

Allocation: Randomized, Endpoint Classification: Safety Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• End-Stage Renal Disease
• Kidney Failure
• Kidney Failure, Chronic
• Renal Insufficiency

Intervention

Biological:
• Single-dose rabbit Anti-thymocyte Globulin induction
6 mg of rATG administered in a single dose on the day of kidney transplantation
• 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.

Locations

Country	Name	City	State
United States	The Methodist Hospital Research Institute	Houston	Texas
United States	University of Nebraska Medical Center	Omaha	Nebraska
United States	University of Arizona	Tucson	Arizona
United States	Wake Forest University	Winston-Salem	North Carolina

Sponsors (6)

Lead Sponsor	Collaborator
Wright State University	Sanofi, The Methodist Hospital System, University of Arizona, University of Nebraska, Wake Forest University

Country where clinical trial is conducted

United States, 

References & Publications (2)

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 2×2 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. — View 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	During first 7 days after kidney transplantation	Yes
Secondary	Patient Survival	Kaplan-Meier estimate of the number of patients who survived for the 12 months after kidney transplantation.	12 months post-transplantation	Yes
Secondary	Graft Survival	Kaplan-Meier estimates of graft survival probability for 12 months after transplantation	12 months post-transplantation	Yes
Secondary	Acute Kidney Rejection	Kaplan-Meier probability estimates of rejection rates	12 months post-transplantation	Yes
Secondary	Incomplete Thymoglobulin Infusion		First 7 days post-transplantation	Yes
Secondary	Kidney Function	Estimated Glomerular Filtration Rate using the abbreviated MDRD formula (Modification of Diet in Renal Disease study)	12 months post-transplantation	No