A Prospective, Open-label, Controlled Multicenter Trial to Assess the Efficacy and Safety of an Induction Regimen of Cyclosporine Micro Emulsion, Enteric-coated Mycophenolate Sodium (EC-MPS) and Corticosteroids, Followed by Administration of Everolimus and Enteric-coated Mycophenolate Sodium (EC-MPS), With Either the Withdrawal of Cyclosporine Micro Emulsion or Corticosteroids in de Novo Kidney Transplant Recipients
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 入组人数
- 126
- 试验地点
- 7
- 主要终点
- Calculated Glomerular Filtration Rate (cGFR) After Kidney Transplant to Evaluate Kidney Function (12 Months Analysis)
研究概览
简要总结
The aim of this study is to assess the safety and efficacy of corticosteroid discontinuation versus cyclosporine micro emulsion discontinuation in recipients receiving reduced exposure cyclosporine micro emulsion and corticosteroids plus enteric-coated mycophenolate sodium (EC-MPS) initially, changed to everolimus at 2 weeks post-transplant. These two groups will be compared to a third control group, who will receive treatment consisting of cyclosporine micro emulsion, enteric-coated mycophenolate sodium (EC-MPS) and steroids.
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
- None
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- 未提供
排除标准
- 未提供
研究组 & 干预措施
Calcineurin Inhibitor (CNI) Withdrawal
Every randomized patient in this group received
Day 1 - Day 14: cyclosporine as Calcineurin Inhibitor (CNI) 5 mg/kg twice daily (b.i.d.), dose adjusted to achieve C2 target of 1,500 ng/mL (range 1,400-1,600 ng/mL) + mycophenolate sodium (MPA)720 mg b.i.d. + methylprednisone/prednisone 500 mg intra-operatively, 250 mg on day 1, then 10-30 mg/day prednisone
Day 15 - Day 60: everolimus 1.5 mg b.i.d. to achieve target 6-10 ng/mL + cyclosporine decrease dose as per protocol guideline + MPA 720 mg b.i.d. until everolimus trough >6 ng/mL, then MPA was stopped + prednisone 10-30mg/day
Day 61 - Day 120: everolimus dose adjusted to achieve target 6-10 ng/mL + cyclosporine 25% dose reduction per fortnight, to be discontinued by day 120 as per protocol (or commence reduction by day 120 at discretion of investigator, to be completed within 2 months of commencement) + prednisone 10-30mg/day Day 121 - Month 36: everolimus dose adjusted to achieve target 8-12 ng/mL + prednisone 5-10 mg/day
干预措施: Everolimus (RAD001) (Drug)
Calcineurin Inhibitor (CNI) Withdrawal
Every randomized patient in this group received
Day 1 - Day 14: cyclosporine as Calcineurin Inhibitor (CNI) 5 mg/kg twice daily (b.i.d.), dose adjusted to achieve C2 target of 1,500 ng/mL (range 1,400-1,600 ng/mL) + mycophenolate sodium (MPA)720 mg b.i.d. + methylprednisone/prednisone 500 mg intra-operatively, 250 mg on day 1, then 10-30 mg/day prednisone
Day 15 - Day 60: everolimus 1.5 mg b.i.d. to achieve target 6-10 ng/mL + cyclosporine decrease dose as per protocol guideline + MPA 720 mg b.i.d. until everolimus trough >6 ng/mL, then MPA was stopped + prednisone 10-30mg/day
Day 61 - Day 120: everolimus dose adjusted to achieve target 6-10 ng/mL + cyclosporine 25% dose reduction per fortnight, to be discontinued by day 120 as per protocol (or commence reduction by day 120 at discretion of investigator, to be completed within 2 months of commencement) + prednisone 10-30mg/day Day 121 - Month 36: everolimus dose adjusted to achieve target 8-12 ng/mL + prednisone 5-10 mg/day
干预措施: Cyclosporine (Calcineurin Inhibitor (CNI)) (Drug)
Calcineurin Inhibitor (CNI) Withdrawal
Every randomized patient in this group received
Day 1 - Day 14: cyclosporine as Calcineurin Inhibitor (CNI) 5 mg/kg twice daily (b.i.d.), dose adjusted to achieve C2 target of 1,500 ng/mL (range 1,400-1,600 ng/mL) + mycophenolate sodium (MPA)720 mg b.i.d. + methylprednisone/prednisone 500 mg intra-operatively, 250 mg on day 1, then 10-30 mg/day prednisone
Day 15 - Day 60: everolimus 1.5 mg b.i.d. to achieve target 6-10 ng/mL + cyclosporine decrease dose as per protocol guideline + MPA 720 mg b.i.d. until everolimus trough >6 ng/mL, then MPA was stopped + prednisone 10-30mg/day
Day 61 - Day 120: everolimus dose adjusted to achieve target 6-10 ng/mL + cyclosporine 25% dose reduction per fortnight, to be discontinued by day 120 as per protocol (or commence reduction by day 120 at discretion of investigator, to be completed within 2 months of commencement) + prednisone 10-30mg/day Day 121 - Month 36: everolimus dose adjusted to achieve target 8-12 ng/mL + prednisone 5-10 mg/day
干预措施: Methylprednisone/prednisone (Drug)
Calcineurin Inhibitor (CNI) Withdrawal
Every randomized patient in this group received
Day 1 - Day 14: cyclosporine as Calcineurin Inhibitor (CNI) 5 mg/kg twice daily (b.i.d.), dose adjusted to achieve C2 target of 1,500 ng/mL (range 1,400-1,600 ng/mL) + mycophenolate sodium (MPA)720 mg b.i.d. + methylprednisone/prednisone 500 mg intra-operatively, 250 mg on day 1, then 10-30 mg/day prednisone
Day 15 - Day 60: everolimus 1.5 mg b.i.d. to achieve target 6-10 ng/mL + cyclosporine decrease dose as per protocol guideline + MPA 720 mg b.i.d. until everolimus trough >6 ng/mL, then MPA was stopped + prednisone 10-30mg/day
Day 61 - Day 120: everolimus dose adjusted to achieve target 6-10 ng/mL + cyclosporine 25% dose reduction per fortnight, to be discontinued by day 120 as per protocol (or commence reduction by day 120 at discretion of investigator, to be completed within 2 months of commencement) + prednisone 10-30mg/day Day 121 - Month 36: everolimus dose adjusted to achieve target 8-12 ng/mL + prednisone 5-10 mg/day
干预措施: Mycophenolate sodium (MPA) (Drug)
Steroid Withdrawal
Every randomized patient in this group received
Day 1 -14: cyclosporine 5 mg/kg b.i.d., dose adjusted to achieve C2 target as per protocol + mycophenolate sodium (MPA) 720 mg b.i.d. + methylprednisone/prednisone 500 mg intra-operatively, 250 mg on day 1, then 10-30 mg prednisone per day
Day 15 - 60: everolimus 1.5 mg b.i.d. to achieve target 6-10 ng/mL + cyclosporine decrease dose as per protocol guideline + MPA 720 mg b.i.d. until everolimus trough >6 ng/mL, then MPA was stopped + prednisone 10-30mg per day
Day 61 - 120: Everolimus dose adjusted + cyclosporine adjust dose according protocol guideline (or commence reduction by day 120 at discretion of Investigator, to be completed within 2 months of commencement) + gradual withdrawal of prednisone by 1 mg/week to be discontinued by Day 120.
Day 121 - Month 36: At Day 121, Month 7 and Month 13 Everolimus dose was adjusted to achieve target 6-10 ng/mL + Cyclosporine adjust dose to achieve C2 target as per protocol
干预措施: Everolimus (RAD001) (Drug)
Steroid Withdrawal
Every randomized patient in this group received
Day 1 -14: cyclosporine 5 mg/kg b.i.d., dose adjusted to achieve C2 target as per protocol + mycophenolate sodium (MPA) 720 mg b.i.d. + methylprednisone/prednisone 500 mg intra-operatively, 250 mg on day 1, then 10-30 mg prednisone per day
Day 15 - 60: everolimus 1.5 mg b.i.d. to achieve target 6-10 ng/mL + cyclosporine decrease dose as per protocol guideline + MPA 720 mg b.i.d. until everolimus trough >6 ng/mL, then MPA was stopped + prednisone 10-30mg per day
Day 61 - 120: Everolimus dose adjusted + cyclosporine adjust dose according protocol guideline (or commence reduction by day 120 at discretion of Investigator, to be completed within 2 months of commencement) + gradual withdrawal of prednisone by 1 mg/week to be discontinued by Day 120.
Day 121 - Month 36: At Day 121, Month 7 and Month 13 Everolimus dose was adjusted to achieve target 6-10 ng/mL + Cyclosporine adjust dose to achieve C2 target as per protocol
干预措施: Cyclosporine (Calcineurin Inhibitor (CNI)) (Drug)
Steroid Withdrawal
Every randomized patient in this group received
Day 1 -14: cyclosporine 5 mg/kg b.i.d., dose adjusted to achieve C2 target as per protocol + mycophenolate sodium (MPA) 720 mg b.i.d. + methylprednisone/prednisone 500 mg intra-operatively, 250 mg on day 1, then 10-30 mg prednisone per day
Day 15 - 60: everolimus 1.5 mg b.i.d. to achieve target 6-10 ng/mL + cyclosporine decrease dose as per protocol guideline + MPA 720 mg b.i.d. until everolimus trough >6 ng/mL, then MPA was stopped + prednisone 10-30mg per day
Day 61 - 120: Everolimus dose adjusted + cyclosporine adjust dose according protocol guideline (or commence reduction by day 120 at discretion of Investigator, to be completed within 2 months of commencement) + gradual withdrawal of prednisone by 1 mg/week to be discontinued by Day 120.
Day 121 - Month 36: At Day 121, Month 7 and Month 13 Everolimus dose was adjusted to achieve target 6-10 ng/mL + Cyclosporine adjust dose to achieve C2 target as per protocol
干预措施: Methylprednisone/prednisone (Drug)
Steroid Withdrawal
Every randomized patient in this group received
Day 1 -14: cyclosporine 5 mg/kg b.i.d., dose adjusted to achieve C2 target as per protocol + mycophenolate sodium (MPA) 720 mg b.i.d. + methylprednisone/prednisone 500 mg intra-operatively, 250 mg on day 1, then 10-30 mg prednisone per day
Day 15 - 60: everolimus 1.5 mg b.i.d. to achieve target 6-10 ng/mL + cyclosporine decrease dose as per protocol guideline + MPA 720 mg b.i.d. until everolimus trough >6 ng/mL, then MPA was stopped + prednisone 10-30mg per day
Day 61 - 120: Everolimus dose adjusted + cyclosporine adjust dose according protocol guideline (or commence reduction by day 120 at discretion of Investigator, to be completed within 2 months of commencement) + gradual withdrawal of prednisone by 1 mg/week to be discontinued by Day 120.
Day 121 - Month 36: At Day 121, Month 7 and Month 13 Everolimus dose was adjusted to achieve target 6-10 ng/mL + Cyclosporine adjust dose to achieve C2 target as per protocol
干预措施: Mycophenolate sodium (MPA) (Drug)
CNI+MPA+ Steroid
Patients randomized to this group received:
Day 1 - Month 36: cyclosporine 5 mg/kg b.i.d., dose adjusted to achieve the protocol defined C2 Targets + mycophenolate sodium 720mg b.i.d. + Methylprednisone/prednisone 500mg intra-operatively, 250mg on day 1, 10-30mg prednisone per day until month 12 (as per local practice), 5-10mg/day months 13-36.
干预措施: Cyclosporine (Calcineurin Inhibitor (CNI)) (Drug)
CNI+MPA+ Steroid
Patients randomized to this group received:
Day 1 - Month 36: cyclosporine 5 mg/kg b.i.d., dose adjusted to achieve the protocol defined C2 Targets + mycophenolate sodium 720mg b.i.d. + Methylprednisone/prednisone 500mg intra-operatively, 250mg on day 1, 10-30mg prednisone per day until month 12 (as per local practice), 5-10mg/day months 13-36.
干预措施: Methylprednisone/prednisone (Drug)
CNI+MPA+ Steroid
Patients randomized to this group received:
Day 1 - Month 36: cyclosporine 5 mg/kg b.i.d., dose adjusted to achieve the protocol defined C2 Targets + mycophenolate sodium 720mg b.i.d. + Methylprednisone/prednisone 500mg intra-operatively, 250mg on day 1, 10-30mg prednisone per day until month 12 (as per local practice), 5-10mg/day months 13-36.
干预措施: Mycophenolate sodium (MPA) (Drug)
结局指标
主要结局
Calculated Glomerular Filtration Rate (cGFR) After Kidney Transplant to Evaluate Kidney Function (12 Months Analysis)
时间窗: At Month 12
The glomerular filtration rate (GFR) was calculated by the Nankivell formula: GFR = 6.7 / Scr + BW / 4 - Surea / 2-100 / (height)\^ 2 + C where Scr is the serum creatinine concentration expressed in mmol/L, BW the body weight in kg, Surea the serum urea in mmol/L, height in m, and the constant C is 35 for male and 25 for female patients.
次要结局
- Calculated Glomerular Filtration Rate (cGFR) After Kidney Transplant to Evaluate Kidney Function (36 Months Analysis)(At Month 24 and 36)
- Number of Participants With Biopsy Proven Acute Rejection (BPAR) Per Treatment Group (12 Months Analysis)(At Month 12)
- Number of Participants With Biopsy Proven Acute Rejection (BPAR) Per Treatment Group (36 Months Analysis)(At Month 12, 24 and 36)
- Number of Participants With Composite Endpoint of Treatment Failure (12 Months Analysis)(Month 12)
- Number of Participants With Composite Endpoint of Treatment Failure (36 Months Analysis)(At Month 12, 24 and 36)
- Number of Participants With Histological Evidence Chronic Allograft Nephropathy (CAN) (12 Months Analysis)(At Month 12)
- Number of Participants With Histological Evidence Chronic Allograft Nephropathy (CAN) (36 Months Analysis)(At Month 36)
- Number of Participants With Sub Clinical Acute Rejection (12 Months Analysis)(At Month 12)
- Number of Participants With Sub Clinical Acute Rejection (36 Months Analysis)(At Month 36)
- Mean Serum Creatinine (12 Months Analysis)(At Month 12)
- Mean Serum Creatinine (36 Months Analysis)(At Month 12, 18, 24 and 36)
- Creatinine Clearance (CrCl) Calculated by the Cockcroft-Gault Formula (12 Months Analysis)(At Month 12)
- Creatinine Clearance Calculated by the Cockcroft-Gault Formula (36 Months Analysis)(At Month 12, 24 and 36)
- Mean Urine Albumin/Creatinine Ratio (ACR) as Measurement of Proteinuria (12 Months Analysis)(At Month 12)
- Mean Urine Albumin/Creatinine Ratio [ACR] as Measurement of Proteinuria (36 Months Analysis)(At Month 12, 18, 24 and 36)
- Number of Participants With Post Transplant Diabetes Mellitus (PTDM) and Impaired Fasting Glucose (12 Months Analysis)(At Month 12)
- Number of Participants With New Onset Diabetes Mellitus After Transplantation (NODAT) and Impaired Fasting Glucose (36 Months Analysis)(At Month 36)
- Number of Participants With Notable Abnormal Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) as Measurement of Effect of Treatment on Cardiovascular Health (12 Months Analysis)(Baseline, Overall post-baseline up to 12 month)
- Number of Participants With Notable Abnormal Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) as Measurement of Effect of Treatment on Cardiovascular Health (36 Months Analysis)(Baseline, Overall post baseline up to Month 36)
- Number of Participants With Erythropoietin Usage (12 Months Analysis)(Month 12)
- Number of Participants With Erythropoietin Usage (36 Months Analysis)(Month 36)
- Mean Short-form 36 Health Survey (SF-36) Score as a Measure of Quality of Life Assessment (12 Months Analysis)(At Month 12)
- Mean Short-form 36 Health Survey (SF-36) Score as a Measure of Quality of Life Assessment (36 Months Analysis)(At Month 24)
- Number of Participants Hospitalized for Reasons Other Than Primary Transplantation (12 Months Analysis)(Month 12)
- Number of Participants Hospitalized for Reasons Other Than Primary Transplantation (36 Months Analysis)(Month 36)
- Number of Participants With Employment Status (12 Months Analysis)(At screening (at day 0 +/- 7 days ), At Month 12)
- Number of Participants With Employment Status (36 Months Analysis)(At screening (at day 0 +/- 7 days ), At Month 36)
- Number of Participants With Wound Problems(12 Months Analysis)(At Month 12)
- Number of Participants With Any Wound Problems (36 Months Analysis)(At Month 12, 24 and 36)
- Number of Participants With Notable Abnormalities in Total Cholesterol and Triglycerides as Measurement of Effect of Treatment on Cardiovascular Health (12 Months Analysis)(Overall post baseline up to month 12)
- Number of Participants With Notable Abnormalities in Total Cholesterol and Triglycerides as Measurement of Effect of Treatment on Cardiovascular Health (36 Months Analysis)(Overall Post Baseline up to month 36)
- Number of Participants With Antibody-mediated Rejection Per Treatment Group (12 Months Analysis)(At Month 12)
- Number of Participants With Antibody-mediated Rejection Per Treatment Group (36 Months Analysis)(At Month 12, 24 and 36)
- Number of Participants With Biopsy Proven Acute Rejection (BPAR) Influenced by Demographic Characteristics and Morbidities (12 Months Analysis)(At Month 12)
- Number of Participants With Biopsy Proven Acute Rejection (BPAR) Influenced by Demographic Characteristics and Morbidities (36 Months Analysis)(At Month 36)
- Number of Patient Survival and Graft Survival (12 Months Analysis)(At Month 12)
- Number of Patient Survival and Graft Survival (36 Months Analysis)(At Month 12, 24 and 36)
- Change in Bone Mineral Density Between Week 2 and Month 24 (36 Months Analysis)(Week 2, Month 24)