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
Overview
- Phase
- Phase 4
- Intervention
- Belatacept
- Conditions
- Implant or Graft; Rejection
- Sponsor
- Columbia University
- Enrollment
- 57
- Locations
- 1
- Primary Endpoint
- Number of Participants With Delayed Graft Function (DGF)
- Status
- Completed
- Last Updated
- 5 years ago
Overview
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.
Investigators
Mark A Hardy
Auchincloss Professor of Surgery
Columbia University
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
Arms & Interventions
Belatacept Immunosuppression
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.
Intervention: Belatacept
Belatacept Immunosuppression
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.
Intervention: Mycophenolate
Belatacept Immunosuppression
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.
Intervention: rATG
Belatacept Immunosuppression
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.
Intervention: Methylprednisolone
Belatacept Immunosuppression
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.
Intervention: Renal transplant
Standard Immunosuppression (Tacrolimus)
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: Tacrolimus
Standard Immunosuppression (Tacrolimus)
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: Mycophenolate
Standard Immunosuppression (Tacrolimus)
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: rATG
Standard Immunosuppression (Tacrolimus)
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: Methylprednisolone
Standard Immunosuppression (Tacrolimus)
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: Renal transplant
Outcomes
Primary Outcomes
Number of Participants With Delayed Graft Function (DGF)
Time Frame: Up to 3 months post-transplantation
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 Outcomes
- Estimated Glomerular Filtration Rate (eGFR)(Up to 1 year post-transplantation)
- Percentage of Participants With Allograft Survival(Up to 1 year post-transplantation)
- Number of Participants With an Allograft Rejection Episode(Up to 1 year post-transplantation)