Belatacept Evaluation of Nephroprotection and Efficacy as First-line Immunosuppression Trial (BENEFIT)
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- 入组人数
- 738
- 试验地点
- 35
- 主要终点
- Percent of Participants Surviving With a Functioning Graft by Month 12
研究概览
简要总结
The purpose of this study is to learn if Belatacept can provide protection from organ rejection following kidney transplantation while avoiding some of the toxic effects of standard immunosuppressive medications such as kidney damage. Effects on kidney function and patient survival as well as drug safety will also be studied.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Single (Participant)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •The subject is a recipient of a living donor or deceased donor kidney transplant.
- •Male or Female, 18 or older
排除标准
- •First time recipient, PRA >- 50% or for retransplantation PRA >- 30%.
- •If retransplantation, previous graft loss cannot be due to acute rejection.
- •Positive cross match.
- •Subject receiving extended criteria donor (ECD) organ
- •For Long-term extension study-Subjects who have completed three years of study treatment (through Week 156)
研究组 & 干预措施
Cyclosporine (CsA)
干预措施: Cyclosporine (CsA) (Drug)
Belatacept LI (less intensive)
干预措施: Belatacept LI (less intensive) (Drug)
Belatacept MI (more intensive)
干预措施: Belatacept MI (more intensive) (Drug)
结局指标
主要结局
Percent of Participants Surviving With a Functioning Graft by Month 12
时间窗: Day 1 to Month 12
Graft loss was defined as either functional loss or physical loss (nephrectomy). Functional loss was defined as a sustained level of serum creatinine (SCr) ≥ 6.0 milligrams per deciliter (mg/dL) or 530 micromolar per liter (μmol/L) as determined by the central laboratory for ≥ 4 weeks or ≥ 56 consecutive days of dialysis or impairment of renal function to such a degree that the participant underwent retransplant.
Percent of Participants With a Composite of Measured Glomerular Filtration Rate (mGFR) Less Than 60 mL/Min/1.73 m^2 at Month 12 or With a Decrease in mGFR Greater Than or Equal to 10 mL/Min/1.73m^2 From Month 3 to Month 12
时间窗: Month 12; Month 3 to Month 12
Measured glomerular filtration rate (mGFR) is the direct measurement of renal function and was assessed by measurement of the clearance of a true glomerular filtration marker (non-radiolabeled iothalamate) using a validated procedure. A GFR of 60 mL/min/1.73 m\^2 was used as the approximate equal of the threshold values of serum creatinine (SCr) of 1.5 mg/dL. A change in GFR of at least 10 mL/min/1.73 m\^2 was used as the approximate change in SCr of at least 0.3 mg/dL. The change component of the composite renal endpoint was assessed from Month 3 to Month 12, since post-transplant renal function is largely stable by Month 3.
Percent of Participants Experiencing Acute Rejection (AR) Post-transplant by Month 12
时间窗: Day 1 to Month 12
Acute rejection was defined as a clinico-pathological event requiring clinical evidence and biopsy confirmation. Clinical evidence was defined if either a or b was satisfied: a: an unexplained rise of serum creatinine ≥ 25% from baseline creatinine; b: an unexplained decreased urine output; or fever and graft tenderness; or a serum creatinine that remains elevated within 14 days post-transplantation and clinical suspicion of acute rejection exists. Allograft biopsies were evaluated by a blinded central independent pathologist using Banff 97 working classification of kidney transplant pathology. Banff 97 diagnostic category for renal allograft biopsies is an international standardized histopathological classification. AR was defined by a renal biopsy demonstrating a Banff 97 classification of Grade IA or greater, with higher scores indicating more severe rejection. Only the episode with the highest Banff grade for each participant was counted.
次要结局
- Mean Change of the Measured Glomerular Filtration Rate (mGFR) From Month 3 to Month 12 and From Month 3 to Month 24(Month 3 to Month 12; Month 3 to Month 24)
- Mean Value of the Measured Glomerular Filtration Rate (mGFR)(Months 3, 12, 24)
- Percent of Participants With Prevalence of Chronic Allograft Nephropathy (CAN) at Month 12(Month 12)
- Number of Participants With Serious Adverse Events, Death, Discontinuation Due to Adverse Events by Month 84(Randomization to Month 84)
- Number of Participants With Adverse Events of Special Interest by Month 84(Randomization to Month 84)
- Mean Blood Pressure at Month 84(Month 84)
- Number of Participants Meeting Marked Laboratory Abnormality Criteria Post-transplant by Month 36(Baseline to Month 36)
- Percent of Participants With Development of Anti-Donor HLA Positive Antibodies by Month 84(Randomization to Month 84)
- Percent of Participants With a Decrease in Measured Glomerular Filtration Rate (mGFR) Greater Than or Equal to 10mL/Min/1.73m^2 From Month 3 to Month 12(Month 3 to Month 12)
- Percent of Participants With a Measured Glomerular Filtration Rate (mGFR) Less Than 60 mL/Min/1.73 m^2 at Month 12(Month 12)
- Mean Value of the Calculated Glomerular Filtration Rate (cGFR) With Imputation(Months 6, 12, 24, 36)
- Mean Value of Lipid Parameters(Months 12, 24, 36)
- Percent of Participants With Prevalence of Dyslipidemia at Month 12(Month 12)
- Percent of Participants Using At Least One Anti-Hyperlipidemic Medication(Month 36)
- Mean Change in Calculated Glomerular Filtration Rate (cGFR) From Month 6 to Month 12(Month 6 to Month 12)
- Percent of Participants With Incidence of New Onset Diabetes Mellitus by Month 36(Week 4 post-transplantation to Month 36)
- Percent of Participants Using At Least One Anti-Hypertensive Medication to Control Hypertension at Month 36(Month 36)
- Percent of Participants With Incidence of Hypertension Post-Transplantation at Month 12(Month 12)
- Percent of Participants With Prevalence of Hypertension Post-Transplantation at Month 12(Month 12)
- Mean Systolic Blood Pressure and Diastolic Blood Pressure(Months 12, 24, 36)
- Percent of Participants With Prevalence of Acute Rejection (AR) by Month 36(Randomization to Month 36)
- Percent of Participants at Baseline With Controlled Hypertension Post Transplantation by Month 12(Day 1 to Month 12)
- Percent of Participants With Prevalence of Controlled Hypertension at Month 12(Month 12)
- Percent of Non-dyslipidemic Participants With Incidence of Dyslipidemia Post-Transplantation by Month 12(Randomization to Month 12)
- Percent of Participants With Controlled Dyslipidemia at Month 12(Month 12)
- Number of Participants With Antihyperlipidemic Medication by Intensity Level(Month 36)
- Mean Changes in the Value of Physical and Mental Components Using SF-36 From Baseline Up To Months 6, 12, 24, and 36(Baseline to Months 6, 12, 24,and 36)
- Mean Change in the Value of the Eight Domain Scores Using SF-36 From Baseline Up To Months 6, 12, 24, and 36(Baseline to Months 6, 12, 24, and 36)
- Percent of Participants Surviving With a Functioning Graft(Months 24, 36)
- Percent of Participants With Composite Endpoint or Death, Graft Loss or Acute Rejection by Month 36(Randomization to Month 36)
- Number of Participants With Acute Rejection (AR) Post-transplant in Terms of Severity Using Banff Grades by Month 36(Randomization to Month 36)
- Percent of Participants Using Polyclonal Antilymphocyte Preparations for Impaired Renal Function and Anticipated Delayed Graft Function by Month 12(Randomization to Month 12)
- Percent of Participants Using Lymphocyte Depleting Therapy (LDT) for the Initial Treatment of Acute Rejection (AR) by Month 36(Randomization to Month 36)
- Percent of Participants With Corticosteroid Resistant Acute Rejection (AR) by Month 36(Randomization to Month 36)
- Number of Participants Who Recovered Completely From an Episode of Acute Rejection (AR) by Month 12(Randomization to Month 12)
- Percent of Participants With Subclinical Rejection at Month 12(Month 12)
- Number of Participants Treated for Acute Rejection (AR) Regardless of Histological Findings by Month 36(Randomization to Month 36)
- Mean Value of Physical and Mental Components Using SF-36 Questionnaire(Months 6, 12, 24, 36)
- Mean Value of the Eight Domain Scores of Quality of Life Using SF-36 Questionnaire(Months 6, 12, 24, 36)
- Mean Relative to an Identified Distribution (Ridit) Value of Symptom Occurrence and Symptom Distress Using Modified Transplant Symptom Occurrence and Symptom Distress Scale (MTSOSDS-59R)(Months 6, 12, 24, 36)