Clinical trial NCT00906204: Safety Trial of Single Versus Multiple Dose Thymoglobulin Induction in Kidney Transplantation
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
Overall status: COMPLETED
Phase: PHASE2
Conditions: End-Stage Renal Disease
Kidney Failure
Keywords: Renal transplantation
Kidney transplantation
Lead sponsor: Wright State University
Sponsor class: OTHER
Collaborators: name: Sanofi
name: University of Arizona
name: Wake Forest University
name: University of Nebraska
name: The Methodist Hospital Research Institute
First posted: 2009-05-21
Enrollment: 99
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Composite Endpoint of 5 Components: Fever, Hypoxia, Hypotension, Cardiac Events, and Delayed Graft Function
timeFrame: During first 7 days after kidney transplantation
Secondary outcomes:
measure: Patient Survival
timeFrame: 12 months post-transplantation
measure: Graft Survival
timeFrame: 12 months post-transplantation
measure: Acute Kidney Rejection
timeFrame: 12 months post-transplantation
measure: Incomplete Thymoglobulin Infusion
timeFrame: First 7 days post-transplantation
measure: Kidney Function
timeFrame: 12 months post-transplantation
Other outcomes:
Locations:
city: Tucson
country: United States
facility: University of Arizona
state: Arizona
city: Omaha
country: United States
facility: University of Nebraska Medical Center
state: Nebraska
city: Winston-Salem
country: United States
facility: Wake Forest University
state: North Carolina
city: Houston
country: United States
facility: The Methodist Hospital Research Institute
state: Texas
Study officials:
affiliation: Wright State University, Dayton, Ohio
name: R.Brian Stevens, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
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.
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.
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.