This study is designed to determine the safety and efficacy of two calcineurin inhibitor free treatment groups 1) a belatacept, everolimus and early corticosteroid withdrawal (ECSWD) immunosuppressive regimen with rabbit antithymocyte globulin induction (rATG) and 2) a belatacept, mycophenolate, chronic steroid regimen with rATG and compare to historical controls of tacrolimus-based and belatacept-based regimens in combination with rATG induction, mycophenolate, and ESWD in renal transplant recipients. The purpose is to evaluate the effect of 2 regimens (rATG induction/belatacept/everolimus/ESWD and rATG induction/belatacept/mycophenolate/CS) on the composite of patient death, graft loss, or eGFR (MDRD) \< 45 mL/min/1.73m2 at Month 12 post-transplantation compared to historical controls of the BEST Trial (groups B and C).
The BETTER trial is designed to determine the safety and efficacy of two calcineurin inhibitor free treatment groups 1) a belatacept, everolimus and early corticosteroid withdrawal (ESWD) immunosuppressive regimen with rabbit antithymocyte globulin induction (rATG) and 2) a belatacept, mycophenolate, chronic steroid regimen with rATG and compare to historical controls of tacrolimus-based and belatacept-based regimens in combination with rATG induction, mycophenolate, and ESWD in renal transplant recipients. Study Hypotheses 1. A belatacept-based immunosuppressive regimen with rATG induction, everolimus and ESWD in renal transplant recipients will lead to less risk of graft loss, patient death, or eGFR \<45ml/min/1.73m2 at 12 and 24 months as compared to a tacrolimus-based immunosuppressive regimen with rATG, mycophenolate, and ESWD in renal transplant recipients (historical control from the BEST Trial-Group C). 2. A belatacept-based immunosuppressive regimen with rATG induction, everolimus and ESWD in renal transplant recipients will lead to less risk of graft loss, patient death, or eGFR \<45ml/min/1.73m2 at 12 and 24 months as compared to a belatacept-based immunosuppressive regimen with rATG and mycophenolate, and ESWD in renal transplant recipients (historical control from the BEST Trial-Group B). 3. A belatacept-based immunosuppressive regimen with rATG, mycophenolate and CS in renal transplant recipients will lead to less risk of graft loss, patient death, or eGFR \<45ml/min/1.73m2 at 12 and 24 months as compared to a tacrolimus-based immunosuppressive regimen with rATG, mycophenolate, and ESWD in renal transplant recipients (historical control from the BEST Trial-Group C). 4. A belatacept-based immunosuppressive regimen with rATG induction, mycophenolate and CS in renal transplant recipients will lead to less risk of graft loss, patient death, or eGFR \<45ml/min/1.73m2 at 12 and 24 months as compared to a belatacept-based immunosuppressive regimen with rATG, mycophenolate, and ESWD in renal transplant recipients (historical control from the BEST Trial-Group B). A controlled, randomized group study is accepted in renal transplantation to evaluate new immunosuppressive regimens versus the current standard of care. Although the ideal study would employ a blinded methodology with a simultaneous control group to minimize bias, the study will not be blinded and evaluates a historical control groups conducted in similar centers. To allow comparison between studies, the primary composite endpoint of death, graft loss, or eGFR \<45ml/min/1.73m2 will be analyzed similarly. The secondary and tertiary endpoints are the similar as well. The BETTER study proposes to compare two additional treatment groups of rATG/belatacept/everolimus/ESWD (Group D) and rATG/belatacept/mycophenolate/CS (Group E) to the historical control Groups B and C. All immunosuppressive agents are approved by the FDA for the prophylaxis of renal transplant rejection, and will be dosed and administered consistent with current clinical practice.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
120
belatacept with everolimus is experimental regimen and it is compared to the labeled regimen of belatacept with mycophenolate with steroids for prevention of rejection in renal transplant recipients
belatacept with everolimus is experimental regimen and it is compared to the labeled regimen of belatacept with mycophenolate with steroids for prevention of rejection in renal transplant recipients
belatacept with mycophenolate is approved regimen for prevention of rejection
belatacept with chronic steroids is approved regimen for prevention of rejection
rabbit antithymocyte globulin induction for prevention of rejection
The Christ Hospital
Cincinnati, Ohio, United States
RECRUITINGUniversity of Cincinnati
Cincinnati, Ohio, United States
RECRUITINGComposite endpoint of patient death, graft loss, or eGFR (MDRD) < 45ml/min mL/min/1.73m2
Number of subjects with composite endpoint of either patient death, graft loss, or eGFR (MDRD) \< 45 mL/min/1.73m2 at Month 12 post-transplantation compared to historical controls of the BEST Trial (groups B and C).
Time frame: 12 months
Incidence of Biopsy-proven acute rejection (BPAR) by Banff 2007 criteria stratified by type (ACR, AMR, or Mixed rejection)
To evaluate, by treatment group at 12 and 24 months incidence of various rejection types
Time frame: 12 and 24 months
Incidence of graft survival censored by patients who died with functioning graft
Incidence of death-censored graft survival not including any patients who died with their graft still functioning
Time frame: 12 and 24 months
# of Patients with eGFR (MDRD) < 30 mL/min/1.73m2
\# of subjects with eGFR (MDRD) \< 30 mL/min/1.73m2
Time frame: 12 and 24 months
# Patients with development of de novo donor specific antibody (DSA)
Patients with development of de novo donor specific antibody (DSA) after transplant
Time frame: 12 and 24 months
Composite endpoint of patient death, graft loss, or estimated eGFR (MDRD) < 45 mL/min/1.73m2 at Month 24 post-transplantation
Composite endpoint of patients with either death, graft loss, or estimated eGFR (MDRD) \< 45 mL/min/1.73m2 at Month 24 post-transplantation
Time frame: 24 months
# Patients with Incidence of Infections
Incidence of infections, including CMV and BK virus
Time frame: 12 and 24 months
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