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

NCT00906204 | Completed Phase 2 Results DMC

• 1 other identifier: 183-09-FB
• Study Type: interventional
• Target: 99
• Locations: 1 country
• Sites: 4

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.

Conditions

End-Stage Renal Disease; Kidney Failure

Keywords

Renal transplantation; Kidney transplantation

Outcome Measures

Primary Outcomes (1)

• 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

Secondary Outcomes (5)

• Patient Survival

  12 months post-transplantation

• Graft Survival

  12 months post-transplantation

• Acute Kidney Rejection

  12 months post-transplantation

• Incomplete Thymoglobulin Infusion

  First 7 days post-transplantation

• Kidney Function

  12 months post-transplantation

Study Arms (2)

Single-dose Thymoglobulin

EXPERIMENTAL

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

Biological: Single-dose rabbit Anti-thymocyte Globulin induction

Divided-dose Thymoglobulin

ACTIVE COMPARATOR

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

Interventions

Single-dose rabbit Anti-thymocyte Globulin induction BIOLOGICAL

6 mg of rATG administered in a single dose on the day of kidney transplantation

Also known as: Thymoglobulin, rATG

Single-dose Thymoglobulin

Divided-dose rabbit Anti-thymocyte Globulin induction BIOLOGICAL

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.

Also known as: Thymoglobulin, rATG

Divided-dose Thymoglobulin

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Wright State University: lead
• Sanofi: collaborator
• University of Arizona: collaborator
• Wake Forest University: collaborator
• University of Nebraska: collaborator
• The Methodist Hospital Research Institute: collaborator

Study Sites (4)

University of Arizona

Tucson, Arizona, 85724, United States

Location

University of Nebraska Medical Center

Omaha, Nebraska, 68198, United States

Location

Wake Forest University

Winston-Salem, North Carolina, 27157, United States

Location

The Methodist Hospital Research Institute

Houston, Texas, 77030, United States

Location

Related Publications (3)

• 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.

  PMID: 18497677 BACKGROUND

• 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.

  PMID: 25083614 BACKGROUND

• 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.

  PMID: 26696251 DERIVED

MeSH Terms

Conditions

Kidney Failure, Chronic; Renal Insufficiency

Interventions

thymoglobulin

Condition Hierarchy (Ancestors)

Renal Insufficiency, Chronic; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Limitations and Caveats

After an interim analysis at the trial mid-point, the trial was terminated because a futility trend analysis showed a \>1.72% chance of the primary endpoint rates between the two groups achieving a significant difference with further enrollment.

Results Point of Contact

• Title: Dr. R. Brian Stevens, MD, PhD, FACS
• Organization: Wright State University Boonshoft School of Medicine, Dayton, Ohio, USA

rbstevens1@icloud.com

937-545-4817

Study Officials

• R.Brian Stevens, MD, PhD

  Wright State University, Dayton, Ohio

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Surgery and Graduate Studies and Director, Transplantation Division

Study Record Dates

• First Submitted: May 19, 2009
• First Posted: May 21, 2009
• Study Start: March 1, 2010
• Primary Completion: July 1, 2014
• Study Completion: July 1, 2014
• Last Updated: December 7, 2015
• Results First Posted: December 7, 2015

Record last verified: 2015-11

Locations

US (4)