Belatacept Compared to Tacrolimus in Deceased Donor Renal Transplant Recipients

NCT ID: NCT02152345

Last Updated: 2021-02-10

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 57 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-06-30
• Study Completion Date: 2016-12-31

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.

Conditions

Implant or Graft; Rejection

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

Belatacept

Intervention Type: DRUG

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.

Mycophenolate

Intervention Type: DRUG

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)

rATG

Intervention Type: DRUG

1.5 mg/kg IV daily on Day 0-3.

(standard of care)

Methylprednisolone

Intervention Type: DRUG

500 mg (Day 0), 250mg (Day 1), 125mg (Day 2), 75 mg (Day 3) IV administered from Day 0-3.

(standard of care)

Renal transplant

Intervention Type: PROCEDURE

Standard organ transplant of a kidney into a patient with end-stage renal disease.

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.

Group Type: ACTIVE_COMPARATOR

Tacrolimus

Intervention Type: DRUG

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)

Mycophenolate

Intervention Type: DRUG

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)

rATG

Intervention Type: DRUG

1.5 mg/kg IV daily on Day 0-3.

(standard of care)

Methylprednisolone

Intervention Type: DRUG

500 mg (Day 0), 250mg (Day 1), 125mg (Day 2), 75 mg (Day 3) IV administered from Day 0-3.

(standard of care)

Renal transplant

Intervention Type: PROCEDURE

Standard organ transplant of a kidney into a patient with end-stage renal disease.

Interventions

Belatacept

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

Tacrolimus

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

Mycophenolate

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

rATG

1.5 mg/kg IV daily on Day 0-3.

(standard of care)

Intervention Type: DRUG

Methylprednisolone

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: DRUG

Renal transplant

Standard organ transplant of a kidney into a patient with end-stage renal disease.

Intervention Type: PROCEDURE

Other Intervention Names

Nulojix; Prograf; Myfortic; induction with rabbit anti-thymocyte globulin; Medrol; Kidney transplant

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Columbia University

OTHER

Sponsor Role: lead

Responsible Party

Mark A Hardy

Auchincloss Professor of Surgery

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Mark A. Hardy, MD

Role: PRINCIPAL_INVESTIGATOR

Columbia University

Locations

Columbia University Medical Center

New York, New York, United States

Countries

United States

Other Identifiers

AAAL7011

Identifier Type: -

Identifier Source: org_study_id