A Randomized, Controlled, Open-Label, Multi-Centre, Parallel-Group Study To Assess All-Cause Mortality And Cardiovascular Morbidity In Patients With Chronic Kidney Disease On Dialysis And Those Not On Renal Replacement Therapy Under Treatment With MIRCERA® Or Reference ESAs.
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 入组人数
- 2,825
- 试验地点
- 196
- 主要终点
- Time to Composite of All-Cause Mortality and Non-Fatal Cardiovascular Events (Myocardial Infarction, Stroke) Defined as Time Between First Dose of Study Medication and Date of Death or Non-Fatal Cardiovascular Events, Whichever Occurred First
研究概览
简要总结
This 2 arm safety study will compare the outcome with respect to a composite endpoint of all-cause mortality and non-fatal cardiovascular events (myocardial infarction, stroke) in CKD participants either on dialysis or not receiving renal replacement therapy under treatment with methoxy polyethylene glycol-epoetin beta or reference ESAs. Participants will be randomized to receive intravenous (iv) or subcutaneous (sc) methoxy polyethylene glycol-epoetin beta at the following doses: for participants not already receiving ESA treatment, methoxy polyethylene glycol-epoetin beta will be administered at a starting dose of 0.6 micrograms per kilograms every 2 weeks (mcg/kg/2wks) iv or sc; for participants receiving maintenance ESA treatment, iv or sc methoxy polyethylene glycol-epoetin beta will be administered at an initial monthly dose of 120, 200 or 360 micrograms (mcg) depending on the weekly dose of ESA received prior to first methoxy polyethylene glycol-epoetin beta administration. Participants randomized to reference ESA treatment will receive iv or sc ESAs in accordance with their prescribed dosing information.
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
- •Male or female participants with symptomatic anemia associated with CKD
- •Participants with renal anemia who are not treated with an ESA:
- •Anemia was defined as hemoglobin (Hb) concentration less than (<) 11.0 grams per deciliter (g/dL) (mean of 2 screening values with at least one day and a maximum of 2 weeks between measurements) with clinical indication for ESA treatment
- •Participants with renal anemia who are on maintenance ESA therapy:
- •If on dialysis: regular long-term hemodialysis or peritoneal dialysis therapy with the same mode of dialysis for at least 3 months before screening
- •Hb concentration between 10 and 12 g/dL (mean of 2 screening values with at least one day and a maximum of 2 weeks between measurements)
- •Participants with adequate iron status defined as: serum ferritin above or equal to 100 micrograms per liter or transferrin saturation above or equal to 20 percent
排除标准
- •Contraindications to ESA treatment: uncontrolled hypertension, hypersensitivity to the active substance or any of the excipients, any other contraindication to ESA therapy
- •Conditions known to cause inadequate response to ESA treatment or anemia other than symptomatic anemia associated with CKD:
- •History of hemoglobinopathy
- •Anemia due to hemolysis
- •Pure red cell aplasia
- •High likelihood of early withdrawal (for example, within 1 year) or interruption of the study
- •Pregnancy or breast-feeding
- •Women of childbearing potential without effective contraception
- •Administration of another investigational drug within 1 month before screening or planned during the study period
研究组 & 干预措施
Erythropoiesis Stimulating Agents
Participants will receive reference ESA according to approved label. The approved reference ESA compounds in the study will be darbepoetin alfa, epoetin alfa and epoetin beta.
干预措施: Darbepoetin Alfa (Drug)
Erythropoiesis Stimulating Agents
Participants will receive reference ESA according to approved label. The approved reference ESA compounds in the study will be darbepoetin alfa, epoetin alfa and epoetin beta.
干预措施: Epoetin Alfa (Drug)
Erythropoiesis Stimulating Agents
Participants will receive reference ESA according to approved label. The approved reference ESA compounds in the study will be darbepoetin alfa, epoetin alfa and epoetin beta.
干预措施: Epoetin Beta (Drug)
Erythropoiesis Stimulating Agents
Participants will receive reference ESA according to approved label. The approved reference ESA compounds in the study will be darbepoetin alfa, epoetin alfa and epoetin beta.
干预措施: methoxy polyethylene glycol-epoetin beta (Drug)
Methoxy Polyethylene Glycol-Epoetin Beta
Participants not currently being treated with an ESA will receive methoxy polyethylene glycol-epoetin beta iv or sc once every 2 weeks for correction of renal anemia (target Hb 10-12 g/dL). Once corrected and in participants currently being treated with an ESA, methoxy polyethylene glycol-epoetin beta will be administered once monthly.
干预措施: Darbepoetin Alfa (Drug)
Methoxy Polyethylene Glycol-Epoetin Beta
Participants not currently being treated with an ESA will receive methoxy polyethylene glycol-epoetin beta iv or sc once every 2 weeks for correction of renal anemia (target Hb 10-12 g/dL). Once corrected and in participants currently being treated with an ESA, methoxy polyethylene glycol-epoetin beta will be administered once monthly.
干预措施: Epoetin Alfa (Drug)
Methoxy Polyethylene Glycol-Epoetin Beta
Participants not currently being treated with an ESA will receive methoxy polyethylene glycol-epoetin beta iv or sc once every 2 weeks for correction of renal anemia (target Hb 10-12 g/dL). Once corrected and in participants currently being treated with an ESA, methoxy polyethylene glycol-epoetin beta will be administered once monthly.
干预措施: methoxy polyethylene glycol-epoetin beta (Drug)
结局指标
主要结局
Time to Composite of All-Cause Mortality and Non-Fatal Cardiovascular Events (Myocardial Infarction, Stroke) Defined as Time Between First Dose of Study Medication and Date of Death or Non-Fatal Cardiovascular Events, Whichever Occurred First
时间窗: Baseline up to approximately 8.5 years
次要结局
- Time to Non-Fatal and Fatal Myocardial Infarction(Baseline up to approximately 8.5 years)
- Time to Non-Fatal and Fatal Stroke(Baseline up to approximately 8.5 years)
- Percentage of Participants With Thromboembolic Events(Baseline up to approximately 8.5 years)
- Time to Non-Fatal Cardiovascular Events (Myocardial Infarction or Stroke, Whichever Occurred First)(Baseline up to approximately 8.5 years)
- Percentage of Participants With Anti-Erythropoietin Antibody-Mediated Pure Red Cell Aplasia (PRCA)(Baseline up to approximately 8.5 years)
- Time to All-Cause Mortality(Baseline up to approximately 8.5 years)
- Percentage of Participants With Gastrointestinal Bleeding(Baseline up to approximately 8.5 years)