Belatacept Compared to Tacrolimus in Deceased Donor Renal Transplant Recipients

Phase 4

Completed

Conditions: Implant or Graft; Rejection

Interventions: Drug: Tacrolimus
Drug: Belatacept
Drug: Mycophenolate
Drug: rATG
Drug: Methylprednisolone
Procedure: Renal transplant

Registration Number: NCT02152345

Lead Sponsor: Columbia University

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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 57

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Standard Immunosuppression (Tacrolimus)	Renal transplant	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.
Belatacept Immunosuppression	Renal transplant	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.
Belatacept Immunosuppression	Mycophenolate	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.
Belatacept Immunosuppression	rATG	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.
Standard Immunosuppression (Tacrolimus)	rATG	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.
Standard Immunosuppression (Tacrolimus)	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.
Standard Immunosuppression (Tacrolimus)	Mycophenolate	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.
Standard Immunosuppression (Tacrolimus)	Methylprednisolone	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.
Belatacept Immunosuppression	Belatacept	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.
Belatacept Immunosuppression	Methylprednisolone	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.

Primary Outcome Measures

Name	Time	Method
Number of Participants With Delayed Graft Function (DGF)	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 Outcome Measures

Name	Time	Method
Estimated Glomerular Filtration Rate (eGFR)	Up to 1 year post-transplantation	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.
Percentage of Participants With Allograft Survival	Up to 1 year post-transplantation	Allograft survival is defined as functioning renal transplant.
Number of Participants With an Allograft Rejection Episode	Up to 1 year post-transplantation	All rejection episodes will be confirmed by renal transplant biopsy provoked by change in renal function not explained by other clinical causes.