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

Phase 2

Completed

Interventions: Biological: Single-dose rabbit Anti-thymocyte Globulin induction
Biological: Divided-dose rabbit Anti-thymocyte Globulin induction

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.

Recruitment & 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.

Arm && Interventions

Group	Intervention	Description
Single-dose Thymoglobulin	Single-dose rabbit Anti-thymocyte Globulin induction	Biological/Vaccine Single-dose rabbit Anti-thymocyte Globulin induction, 6 mg/kg IV infusion
Divided-dose Thymoglobulin	Divided-dose rabbit Anti-thymocyte Globulin induction	Biological/Vaccine Divided-dose rabbit Anti-thymocyte Globulin induction, 1.5 mg/kg IV infusion QD x 4

Primary Outcome Measures

Name	Time	Method
Composite Endpoint of 5 Components: Fever, Hypoxia, Hypotension, Cardiac Events, and Delayed Graft Function	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

Secondary Outcome Measures

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

Locations (4): University of Arizona
🇺🇸
Tucson, Arizona, United States
University of Nebraska Medical Center
🇺🇸
Omaha, Nebraska, United States
Wake Forest University
🇺🇸
Winston-Salem, North Carolina, United States
The Methodist Hospital Research Institute
🇺🇸
Houston, Texas, United States
University of Arizona
🇺🇸Tucson, Arizona, United States