A National, Multi-center, Randomized, Open Label Study to Evaluate the Efficacy and Safety of Everolimus Combined With Enteric-coated Mycophenolate Sodium Compared to the Standard Treatment Combining Tacrolimus and Enteric-coated Mycophenolate Sodium in de Novo Liver Transplant Recipients
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 188
- 试验地点
- 1
- 主要终点
- Change From Baseline (Randomization) in Renal Function
研究概览
简要总结
The aims of the study was to evaluate the safety and efficacy of early introduction one month post-transplantation of everolimus associated to EC-MPS with tacrolimus discontinuation in de novo liver transplant recipients and to evaluate if it leads to a better renal function 6 month post-transplantation compared to standard treatment associating tacrolimus and EC-MPS.
The renal function was estimated by glomerular filtration rate.
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 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Man or woman aged 18 years or greater, recipient of a primary liver transplant from a deceased donor with whole or split liver
排除标准
- •Patient recipient of multiple solid organ or islet cell tissue transplants, or have previously received an organ or tissue transplant
- •Recipient of a liver from a living donor or cadaveric non heart beating donor
- •ABO incompatible transplant graft
- •Transplantation following autoimmune liver hepatitis, primitive sclerosing cholangitis or primitive biliary cirrhosis
- •Estimated glomerular filtration rate ≤ 30ml/min at selection
- •History of malignancy within the 5 past years, other than non-metastatic basal or squamous cell carcinoma and hepatocellular carcinoma
- •Alpha-foeto-protein > 1000 ng/ml (only in case of hepatocellular carcinoma)
研究组 & 干预措施
Tacrolimus
From transplantation to randomization: Basiliximab (40mg) at Day 0 and Day 4 + tacrolimus (C0 6-10 ng/ml) from Day 3-Day 5 + mycophenolic acid 1440 mg/d ± oral corticosteroids. From randomization to month 6 : tacrolimus (C0 6-10 ng/ml) + mycophenolic acid 1440 mg/d ± oral corticosteroids
干预措施: tacrolimus (Drug)
Tacrolimus
From transplantation to randomization: Basiliximab (40mg) at Day 0 and Day 4 + tacrolimus (C0 6-10 ng/ml) from Day 3-Day 5 + mycophenolic acid 1440 mg/d ± oral corticosteroids. From randomization to month 6 : tacrolimus (C0 6-10 ng/ml) + mycophenolic acid 1440 mg/d ± oral corticosteroids
干预措施: Basiliximab (Drug)
Tacrolimus
From transplantation to randomization: Basiliximab (40mg) at Day 0 and Day 4 + tacrolimus (C0 6-10 ng/ml) from Day 3-Day 5 + mycophenolic acid 1440 mg/d ± oral corticosteroids. From randomization to month 6 : tacrolimus (C0 6-10 ng/ml) + mycophenolic acid 1440 mg/d ± oral corticosteroids
干预措施: Mycophenolic Acid (Drug)
Tacrolimus
From transplantation to randomization: Basiliximab (40mg) at Day 0 and Day 4 + tacrolimus (C0 6-10 ng/ml) from Day 3-Day 5 + mycophenolic acid 1440 mg/d ± oral corticosteroids. From randomization to month 6 : tacrolimus (C0 6-10 ng/ml) + mycophenolic acid 1440 mg/d ± oral corticosteroids
干预措施: Corticosteroids (Drug)
Everolimus (RAD001)
From transplantation to randomization: Basiliximab (40mg) at Day 0 and Day 4 + tacrolimus (C0 6-10 ng/ml) from Day 3-Day 5 + mycophenolic acid 1440 mg/d ± oral corticosteroids.
From randomization to month 6 : everolimus (recommended starting dose of 2 mg/day, then adjusted to achieve the target 6 ≤ C0 ≤ 10 ng/mL, until W24) + mycophenolic acid 1440 mg/d ± oral corticosteroids. The dose of tacrolimus was reduced by 50% twice: at the introduction of everolimus and at week 8 post-transplantation. Tacrolimus had to be finally discontinued in week 12 post-transplantation (by week 16 at the latest).
干预措施: tacrolimus (Drug)
Everolimus (RAD001)
From transplantation to randomization: Basiliximab (40mg) at Day 0 and Day 4 + tacrolimus (C0 6-10 ng/ml) from Day 3-Day 5 + mycophenolic acid 1440 mg/d ± oral corticosteroids.
From randomization to month 6 : everolimus (recommended starting dose of 2 mg/day, then adjusted to achieve the target 6 ≤ C0 ≤ 10 ng/mL, until W24) + mycophenolic acid 1440 mg/d ± oral corticosteroids. The dose of tacrolimus was reduced by 50% twice: at the introduction of everolimus and at week 8 post-transplantation. Tacrolimus had to be finally discontinued in week 12 post-transplantation (by week 16 at the latest).
干预措施: everolimus (Drug)
Everolimus (RAD001)
From transplantation to randomization: Basiliximab (40mg) at Day 0 and Day 4 + tacrolimus (C0 6-10 ng/ml) from Day 3-Day 5 + mycophenolic acid 1440 mg/d ± oral corticosteroids.
From randomization to month 6 : everolimus (recommended starting dose of 2 mg/day, then adjusted to achieve the target 6 ≤ C0 ≤ 10 ng/mL, until W24) + mycophenolic acid 1440 mg/d ± oral corticosteroids. The dose of tacrolimus was reduced by 50% twice: at the introduction of everolimus and at week 8 post-transplantation. Tacrolimus had to be finally discontinued in week 12 post-transplantation (by week 16 at the latest).
干预措施: Basiliximab (Drug)
Everolimus (RAD001)
From transplantation to randomization: Basiliximab (40mg) at Day 0 and Day 4 + tacrolimus (C0 6-10 ng/ml) from Day 3-Day 5 + mycophenolic acid 1440 mg/d ± oral corticosteroids.
From randomization to month 6 : everolimus (recommended starting dose of 2 mg/day, then adjusted to achieve the target 6 ≤ C0 ≤ 10 ng/mL, until W24) + mycophenolic acid 1440 mg/d ± oral corticosteroids. The dose of tacrolimus was reduced by 50% twice: at the introduction of everolimus and at week 8 post-transplantation. Tacrolimus had to be finally discontinued in week 12 post-transplantation (by week 16 at the latest).
干预措施: Mycophenolic Acid (Drug)
Everolimus (RAD001)
From transplantation to randomization: Basiliximab (40mg) at Day 0 and Day 4 + tacrolimus (C0 6-10 ng/ml) from Day 3-Day 5 + mycophenolic acid 1440 mg/d ± oral corticosteroids.
From randomization to month 6 : everolimus (recommended starting dose of 2 mg/day, then adjusted to achieve the target 6 ≤ C0 ≤ 10 ng/mL, until W24) + mycophenolic acid 1440 mg/d ± oral corticosteroids. The dose of tacrolimus was reduced by 50% twice: at the introduction of everolimus and at week 8 post-transplantation. Tacrolimus had to be finally discontinued in week 12 post-transplantation (by week 16 at the latest).
干预措施: Corticosteroids (Drug)
结局指标
主要结局
Change From Baseline (Randomization) in Renal Function
时间窗: Baseline, Week 24
Change in renal function was measured by change in glomerular filtration rate (GFR). GFR calculated using the abbreviated modification of diet in renal disease (aMDRD) formula. GFR in mL/min/1.73m\^2 for men of non-black ethnicity: 186 \* \[C/88\]\^-1.154 \* \[A\]\^-0.023\*G\*R ; C = serum creatinine (in μmol/L); A = Age (in years). G = 0.742 when the patient is a women; Otherwise G=1 R= 1.21 when the patient was of black ethnicity; Otherwise R = 1 Baseline was Day 28 visit.
次要结局
- Change From Baseline (Randomization) in Glomerular Filtration Rate Estimated by CKD-EPI Formula(Baseline, Week 24)
- Number of Patients in Different Stages of Chronic Kidney Diseases According to the K/DOQI Classification System(At Week 24)
- Number of Patients With Any Adverse Events, Serious Adverse Events, Death and Premature Discontinuation(Baseline to 24 weeks)
- Number of Patients With Treatment Failures(At week 12 and week 24)
- Number of Patients With Treated or Not Treated Biopsy Proven Acute Rejection (BPAR)(at 12 week and 24 week)
- Number of Patients Reported With Different Categories of Severity of BPAR According to Banff Classification(at 12 week and 24 week)
- Number of Patients With Treated or Untreated BPAR With RAI Score Greater Than 3(At 24 weeks)
- Number of Patients With Death or Graft Loss(at week 24)
- Change From Baseline (Randomization) in Serum Creatinine(Baseline, Week 24)
- Change From Baseline (Randomization) in Urine Protein/Creatinine Ratio(Baseline, week 24)
- Change From Baseline (Randomization) in Creatinine Clearance Estimated Using the Adjusted Cockcroft-Gault Formula(Baseline, Week 24)
- Change From Baseline (Randomization) in Glomerular Filtration Rate Estimated by Abbreviated Modification of Diet in Renal Disease (MDRD) Formula(Baseline, Week 24)