Extension Study to the Multicenter, Open-label, Randomized, Controlled Study CRAD001H2304 to Evaluate the Long-term Efficacy and Safety of Concentration-controlled Everolimus in Liver Transplant Recipient
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 284
- 试验地点
- 1
- 主要终点
- Incidence Rate of Composite Efficacy Failure Defined as Treated Biopsy Proven Acute Rejection (tBPAR ), Graft Loss or Death
研究概览
简要总结
The reason for this extension is to evaluate the long-term safety and efficacy of two concentration-controlled everolimus regimen in de novo liver transplant recipients. The most important long-term safety assessments include evaluation of renal function, progression of HCV related allograft fibrosis, and other treatment related effects at Month 36 post-transplantation compared to extension baseline (Months 24 post-transplantation).
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
- 20 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Written informed consent
- •Ability and willingness to adhere to study regimen
- •Completed core study with assigned regimen;
排除标准
- •Patients fulfilling any of the following criteria are not eligible for inclusion in this study:
- •Severe hypercholesterolemia or hypertriglyceridemia.
- •Low platelet count.
- •Low white blood cell count.
- •Positive test for human immunodeficiency virus (HIV).
- •Systemic infection requiring active use of IV antibiotics.
- •Patients in a critical care setting.
- •Use of prohibited medication.
- •Use of immunosuppressive agents not utilized in the protocol.
- •Hypersensitivity to any of the study drugs or similar drugs.
- •Pregnant or nursing (lactating) women
- •Women of child-bearing potential not using a highly effective method of birth control.
- •Other protocol-defined inclusion/exclusion criteria may apply
研究组 & 干预措施
Everolimus + reduced tacrolimus
Participants were maintained on whole blood trough levels of 3 - 8 ng/mL everolimus and 3 - 5 ng/mL tacrolimus.
干预措施: Tacrolimus (reduced tacrolimus) (Drug)
Everolimus + reduced tacrolimus
Participants were maintained on whole blood trough levels of 3 - 8 ng/mL everolimus and 3 - 5 ng/mL tacrolimus.
干预措施: Everolimus (reduced tacrolimus) (Drug)
Everolimus + reduced tacrolimus
Participants were maintained on whole blood trough levels of 3 - 8 ng/mL everolimus and 3 - 5 ng/mL tacrolimus.
干预措施: Corticosteroids (Drug)
Tacrolimus elimination
Participants were maintained on a whole blood trough level of 6 - 10 ng/mL everolimus.
干预措施: Tacrolimus (tacrolimus elimination) (Drug)
Tacrolimus elimination
Participants were maintained on a whole blood trough level of 6 - 10 ng/mL everolimus.
干预措施: Everolimus (tacrolimus elimination) (Drug)
Tacrolimus elimination
Participants were maintained on a whole blood trough level of 6 - 10 ng/mL everolimus.
干预措施: Corticosteroids (Drug)
Tacrolimus control
Participants were maintained on a whole blood trough level of 6 - 10 ng/mL tacrolimus.
干预措施: Tacrolimus (tacrolimus control) (Drug)
Tacrolimus control
Participants were maintained on a whole blood trough level of 6 - 10 ng/mL tacrolimus.
干预措施: Corticosteroids (Drug)
结局指标
主要结局
Incidence Rate of Composite Efficacy Failure Defined as Treated Biopsy Proven Acute Rejection (tBPAR ), Graft Loss or Death
时间窗: from months 36 to 48
The number of participants who experienced composite efficacy failure was analyzed. Composite efficacy failure was defined as treated biopsy proven acute rejection (tBPAR), graft loss, or death. A BPAR was defined as an acute rejection confirmed by biopsy with a Rejection Activity Index (RAI) score ≥ 3. tBPAR was defined as a BPAR which was treated with anti-rejection therapy. The RAI is used to score liver biopsies with acute rejection and is composed of 3 categories (portal inflammation, bile duct inflammation damage, and venous endothelial inflammation) each scored on a scale of 0 (absent) to 3 (severe) by a trained pathologist. The total RAI score = the sum of the scores of the 3 categories and ranges from 0 to 9, with a higher score indicating greater rejection. The graft was presumed to be lost on the day the patient was newly listed for a liver graft, received a graft re-transplant, or died.
Incidence Rate of Composite Efficacy Failure Defined as Graft Loss or Death
时间窗: from months 36 - 48
The number of participants who experienced graft loss or death was analyzed. The graft was presumed to be lost on the day the patient was newly listed for a liver graft, received a graft re-transplant, or died.
Change in Renal Function
时间窗: from months 24 to 36
Change in renal function was assessed by the estimated Glomerular Filtration Rate (eGFR) using the abbreviated (4 variables) Modification of Diet in Renal Disease (MDRD-4) formula which was developed by the MDRD Study Group and has been validated in patients with chronic kidney disease. The MDRD-4 formula used for the eGFR calculation is: eGFR (mL/min/1.73m\^2) = 186.3\*(C\^-1.154)\*(A\^-0.203)\*G\*R, where C is the serum concentration of creatinine (mg/dL), A is age (years), G=0.742 when gender is female, otherwise G=1, R=1.21 when race is black, otherwise R=1.
次要结局
- Incidence Rate of tBPAR(from months 24 - 36)