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Belatacept Compared to Tacrolimus in Deceased Donor Renal Transplant Recipients

Primary Purpose

Implant or Graft; Rejection

Status
Completed
Phase
Phase 4
Locations
United States
Study Type
Interventional
Intervention
Belatacept
Tacrolimus
Mycophenolate
rATG
Methylprednisolone
Renal transplant
Sponsored by
Columbia University
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Implant or Graft; Rejection focused on measuring kidney, renal, transplant, belatacept, delayed graft function, thymoglobulin, tacrolimus, kidney function, immunosuppression, NGAL

Eligibility Criteria

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

Inclusion Criteria:

  • Patients must have known Epstein-Barr virus (EBV) serostatus, and that status must be positive
  • Adult patients ≥18 years of age, receiving a deceased donor kidney transplant at Columbia University Medical Center (CUMC)
  • Patients with a PRA ≤ of 50
  • Primary or re-transplant candidates (no more than 5th renal transplant)
  • Deceased donor renal transplant recipients
  • Candidates eligible for rATG induction
  • Patients fully consented prior to transplantation
  • Women of reproductive age who are willing to delay pregnancy for the duration of the study and use appropriate recommended contraception

Exclusion Criteria:

  • Seronegative or unknown EBV serologic status (due to the risk of post-transplant lymphoproliferative disorder, PTLD), predominantly involving the central nervous system.
  • Patients with tuberculosis who have not been treated for latent infection.
  • Scheduled to undergo multi-organ transplantation
  • Recipients of previous non-renal organ transplant
  • Patient receiving 5th renal transplant at the time of screening.
  • Patients with a PRA > 50
  • Recipient is pre-emptive status.
  • Recipient with positive flow crossmatch.
  • History or known HIV
  • Known hypersensitivity or contra-indications to Belatacept, Tacrolimus, Mycophenolate mofetil (cellcept), or mycophenolic acid
  • Use of an investigational drug in the past 30 days before day of surgery
  • Enrolled in a clinical trial other than the current
  • Lactating or pregnant women
  • Donor specific antibodies (DSA) identified at the time of transplantation
  • ABO incompatible renal transplant

Sites / Locations

  • Columbia University Medical Center

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

Belatacept Immunosuppression

Standard Immunosuppression (Tacrolimus)

Arm Description

Renal transplant recipients will receive steroids (Methylprednisolone), rATG, Belatacept and Mycophenolate. Subjects will be followed for primary endpoint to Day 7 and Month 3 after transplantation and secondary endpoints of kidney function and patient and graft survival up to month 36 after transplantation.

Renal transplant recipients will receive standard immunosuppressive therapy, including steroids (Methylprednisolone), rATG, Tacrolimus and Mycophenolate. Subjects will be followed for primary endpoint to Day 7 and Month 3 after transplantation and secondary endpoints of kidney function and patient and graft survival up to month 36 after transplantation.

Outcomes

Primary Outcome Measures

Number of Participants With Delayed Graft Function (DGF)
To assess whether treatment with Thymoglobulin induction and belatacept based maintenance immunosuppression would reduce delayed graft function (DGF) rates among recipients of deceased donor renal transplants as measured by clinical findings and NGAL marker, as specified below and defined by others. This will be compared to the incidence of DGF in patients treated with a Tacrolimus based regimen. Patients who require hemodialysis in the first 7 days after transplantation and/or patients whose serum creatinine decreases <10% during 3 consecutive days after the transplant will be considered to have DGF in the absence of other confounding factors such as obstruction or infection. NGAL will be used as a verification marker of DGF.

Secondary Outcome Measures

Percentage of Participants With Allograft Survival
Allograft survival is defined as functioning renal transplant.
Number of Participants With an Allograft Rejection Episode
All rejection episodes will be confirmed by renal transplant biopsy provoked by change in renal function not explained by other clinical causes.
Estimated Glomerular Filtration Rate (eGFR)
Estimated glomerular filtration rate (eGFR) is based on a blood sample (serum creatinine value), age, race, and gender. eGFR estimates best the function of the kidney at any one time.

Full Information

First Posted
May 29, 2014
Last Updated
January 26, 2021
Sponsor
Columbia University
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1. Study Identification

Unique Protocol Identification Number
NCT02152345
Brief Title
Belatacept Compared to Tacrolimus in Deceased Donor Renal Transplant Recipients
Official Title
A Randomized Clinical Trial of Efficacy and Safety on the Use of Belatacept as Compared to Tacrolimus in the Setting of Rabbit Antithymocyte Globulin Induction and Rapid Steroid Discontinuation in Deceased Donor Renal Transplant Recipients With a Focus on Ameliorating Delayed Graft Function
Study Type
Interventional

2. Study Status

Record Verification Date
January 2021
Overall Recruitment Status
Completed
Study Start Date
June 2014 (undefined)
Primary Completion Date
December 31, 2016 (Actual)
Study Completion Date
December 31, 2016 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Columbia University

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
The main purpose of this study is to find out whether treatment to prevent kidney rejection with belatacept in presence of Thymoglobulin induction and withdrawal of steroids will result in less delayed graft function or "sleepy kidney" after transplant than that seen in patients who get tacrolimus as their main drug to prevent rejection instead of belatacept. The investigators will also look at whether patients who get belatacept have the same, lesser or more problems that those who get tacrolimus.
Detailed Description
New York Presbyterian Hospital-Columbia University Medical Center (NYPH-CUMC) performs nearly 250 renal transplants annually; of these approximately half are recipients of a variety of deceased donor kidneys, usually with cold ischemia time (CIT) >24 hours leading to an approximate incidence of delayed graft function (DGF) of 50%. The main focus of this study will be to determine whether initial immunosuppression with belatacept with Thymoglobulin induction will result in lower incidence and/or more rapid disappearance of DGF than that observed in patients who receive tacrolimus based immunosuppression. NGAL determinations will bne made in the first months after transplantation to correlate with clinical DGF.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Implant or Graft; Rejection
Keywords
kidney, renal, transplant, belatacept, delayed graft function, thymoglobulin, tacrolimus, kidney function, immunosuppression, NGAL

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
57 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Belatacept Immunosuppression
Arm Type
Experimental
Arm Description
Renal transplant recipients will receive steroids (Methylprednisolone), rATG, Belatacept and Mycophenolate. Subjects will be followed for primary endpoint to Day 7 and Month 3 after transplantation and secondary endpoints of kidney function and patient and graft survival up to month 36 after transplantation.
Arm Title
Standard Immunosuppression (Tacrolimus)
Arm Type
Active Comparator
Arm Description
Renal transplant recipients will receive standard immunosuppressive therapy, including steroids (Methylprednisolone), rATG, Tacrolimus and Mycophenolate. Subjects will be followed for primary endpoint to Day 7 and Month 3 after transplantation and secondary endpoints of kidney function and patient and graft survival up to month 36 after transplantation.
Intervention Type
Drug
Intervention Name(s)
Belatacept
Other Intervention Name(s)
Nulojix
Intervention Description
Belatacept 10 mg/kg will be administered in the operating room approximately 1 hour prior to kidney allograft reperfusion (Day 0). It will then be administered at 10 mg/kg on the following post-transplantation days: Day 5, 14, 30, 56, and 84. Belatacept 5 mg/kg will be administered every four weeks thereafter until end of study.
Intervention Type
Drug
Intervention Name(s)
Tacrolimus
Other Intervention Name(s)
Prograf
Intervention Description
Tacrolimus 0.05 mg/kg by mouth every 12 hours will be on Day 0 after transplantation. It will then be administered at 8-12 ng/mL on the following post-transplantation days: Day 3-90; at 8-10 ng/mL Day 91-180. Tacrolimus 6 - 8 ng/mL will be administered daily thereafter until end of study. (standard of care)
Intervention Type
Drug
Intervention Name(s)
Mycophenolate
Other Intervention Name(s)
Myfortic
Intervention Description
An immunosuppressive agent used with other medicines to lower the body's natural immunity in patients who receive kidney transplants. 720 mg by mouth every 12 hours (Day 0)(1080 mg AA). (standard of care)
Intervention Type
Drug
Intervention Name(s)
rATG
Other Intervention Name(s)
induction with rabbit anti-thymocyte globulin
Intervention Description
1.5 mg/kg IV daily on Day 0-3. (standard of care)
Intervention Type
Drug
Intervention Name(s)
Methylprednisolone
Other Intervention Name(s)
Medrol
Intervention Description
500 mg (Day 0), 250mg (Day 1), 125mg (Day 2), 75 mg (Day 3) IV administered from Day 0-3. (standard of care)
Intervention Type
Procedure
Intervention Name(s)
Renal transplant
Other Intervention Name(s)
Kidney transplant
Intervention Description
Standard organ transplant of a kidney into a patient with end-stage renal disease.
Primary Outcome Measure Information:
Title
Number of Participants With Delayed Graft Function (DGF)
Description
To assess whether treatment with Thymoglobulin induction and belatacept based maintenance immunosuppression would reduce delayed graft function (DGF) rates among recipients of deceased donor renal transplants as measured by clinical findings and NGAL marker, as specified below and defined by others. This will be compared to the incidence of DGF in patients treated with a Tacrolimus based regimen. Patients who require hemodialysis in the first 7 days after transplantation and/or patients whose serum creatinine decreases <10% during 3 consecutive days after the transplant will be considered to have DGF in the absence of other confounding factors such as obstruction or infection. NGAL will be used as a verification marker of DGF.
Time Frame
Up to 3 months post-transplantation
Secondary Outcome Measure Information:
Title
Percentage of Participants With Allograft Survival
Description
Allograft survival is defined as functioning renal transplant.
Time Frame
Up to 1 year post-transplantation
Title
Number of Participants With an Allograft Rejection Episode
Description
All rejection episodes will be confirmed by renal transplant biopsy provoked by change in renal function not explained by other clinical causes.
Time Frame
Up to 1 year post-transplantation
Title
Estimated Glomerular Filtration Rate (eGFR)
Description
Estimated glomerular filtration rate (eGFR) is based on a blood sample (serum creatinine value), age, race, and gender. eGFR estimates best the function of the kidney at any one time.
Time Frame
Up to 1 year post-transplantation

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Patients must have known Epstein-Barr virus (EBV) serostatus, and that status must be positive Adult patients ≥18 years of age, receiving a deceased donor kidney transplant at Columbia University Medical Center (CUMC) Patients with a PRA ≤ of 50 Primary or re-transplant candidates (no more than 5th renal transplant) Deceased donor renal transplant recipients Candidates eligible for rATG induction Patients fully consented prior to transplantation Women of reproductive age who are willing to delay pregnancy for the duration of the study and use appropriate recommended contraception Exclusion Criteria: Seronegative or unknown EBV serologic status (due to the risk of post-transplant lymphoproliferative disorder, PTLD), predominantly involving the central nervous system. Patients with tuberculosis who have not been treated for latent infection. Scheduled to undergo multi-organ transplantation Recipients of previous non-renal organ transplant Patient receiving 5th renal transplant at the time of screening. Patients with a PRA > 50 Recipient is pre-emptive status. Recipient with positive flow crossmatch. History or known HIV Known hypersensitivity or contra-indications to Belatacept, Tacrolimus, Mycophenolate mofetil (cellcept), or mycophenolic acid Use of an investigational drug in the past 30 days before day of surgery Enrolled in a clinical trial other than the current Lactating or pregnant women Donor specific antibodies (DSA) identified at the time of transplantation ABO incompatible renal transplant
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Mark A. Hardy, MD
Organizational Affiliation
Columbia University
Official's Role
Principal Investigator
Facility Information:
Facility Name
Columbia University Medical Center
City
New York
State/Province
New York
ZIP/Postal Code
10032
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

Belatacept Compared to Tacrolimus in Deceased Donor Renal Transplant Recipients

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