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Belatacept Compared to Tacrolimus in Deceased Donor Renal Transplant Recipients

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ClinicalTrials.gov Identifier: NCT02152345
Recruitment Status : Completed
First Posted : June 2, 2014
Results First Posted : September 10, 2019
Last Update Posted : September 10, 2019
Sponsor:
Information provided by (Responsible Party):
Mark Hardy, 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.

Condition or disease Intervention/treatment Phase
Implant or Graft; Rejection Drug: Belatacept Drug: Tacrolimus Drug: Mycophenolate Drug: rATG Drug: Methylprednisolone Procedure: Renal transplant Phase 4

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 57 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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 Start Date : June 2014
Actual Primary Completion Date : December 31, 2016
Actual Study Completion Date : December 31, 2016

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: 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.
Drug: 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.

Other Name: Nulojix

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)

Other Name: Myfortic

Drug: rATG

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

(standard of care)

Other Name: induction with rabbit anti-thymocyte globulin

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)

Other Name: Medrol

Procedure: Renal transplant
Standard organ transplant of a kidney into a patient with end-stage renal disease.
Other Name: Kidney transplant

Active Comparator: 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.
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)

Other Name: Prograf

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)

Other Name: Myfortic

Drug: rATG

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

(standard of care)

Other Name: induction with rabbit anti-thymocyte globulin

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)

Other Name: Medrol

Procedure: Renal transplant
Standard organ transplant of a kidney into a patient with end-stage renal disease.
Other Name: Kidney transplant




Primary Outcome Measures :
  1. Delayed Graft Function (DGF) Rate [ 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 Outcome Measures :
  1. Percentage of Participants With Allograft Survival [ Time Frame: Up to 1 year post-transplantation ]
    Allograft survival is defined as functioning renal transplant.

  2. Number of Participants With an Allograft Rejection Episode [ Time Frame: 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.

  3. Estimated Glomerular Filtration Rate (eGFR) [ Time Frame: 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.



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02152345


Locations
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United States, New York
Columbia University Medical Center
New York, New York, United States, 10032
Sponsors and Collaborators
Columbia University
Investigators
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Principal Investigator: Mark A Hardy, MD Columbia University

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Responsible Party: Mark Hardy, Auchincloss Professor of Surgery, Columbia University
ClinicalTrials.gov Identifier: NCT02152345     History of Changes
Other Study ID Numbers: AAAL7011
First Posted: June 2, 2014    Key Record Dates
Results First Posted: September 10, 2019
Last Update Posted: September 10, 2019
Last Verified: August 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Keywords provided by Mark Hardy, Columbia University:
kidney
renal
transplant
belatacept
delayed graft function
thymoglobulin
tacrolimus
kidney function
immunosuppression
NGAL
Additional relevant MeSH terms:
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Delayed Graft Function
Pathologic Processes
Mycophenolic Acid
Methylprednisolone
Methylprednisolone Acetate
Methylprednisolone Hemisuccinate
Prednisolone
Prednisolone acetate
Abatacept
Tacrolimus
Prednisolone hemisuccinate
Prednisolone phosphate
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Calcineurin Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antibiotics, Antineoplastic
Antineoplastic Agents
Antibiotics, Antitubercular
Antitubercular Agents
Anti-Bacterial Agents
Anti-Infective Agents
Anti-Inflammatory Agents
Antiemetics
Autonomic Agents
Peripheral Nervous System Agents
Gastrointestinal Agents
Glucocorticoids