Utilizing Lipid-lowering Therapy With Moderate-intensity Statin Plus Ezetimibe in Chronic Kidney Disease Patients With Concomitant Atherosclerotic Cardiovascular Disease: ULTRA-CKD Trial
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 1,952
- 试验地点
- 1
- 主要终点
- Major adverse cardiovascular events
研究概览
简要总结
The ULTRA-CKD trial is a prospective, randomized, open-label, multicenter trial designed to compare the efficacy and safety of moderate-intensity statin plus ezetimibe combination therapy versus high-intensity statin monotherapy in patients with chronic kidney disease (CKD) and concomitant atherosclerotic cardiovascular disease (ASCVD).
Patients with CKD are at very high risk for ASCVD. In this population, it is important to establish a lipid-lowering strategy that optimizes cardiovascular outcomes while ensuring long-term safety. While high-intensity statins are generally considered as initial treatment option for secondary prevention, the optimal strategy for CKD patients remains to be clinicaly defined. This study aims to evaluate whether the combination of moderate-intensity statin and ezetimibe is non-inferior to high-intensity statin monotherapy in terms of 3-year composite of major adverse cardiovascular events.
详细描述
All eligible patients with chronic kidney disease (CKD) and concomitant atherosclerotic cardiovascular disease (ASCVD) will be enrolled according to inclusion/exclusion criteria after voluntary agreement with informed consent.
At the time of enrollment, we will stratify the patients according to diabetes mellitus and dialysis status, and randomly assign them in two groups according to lipid-lowering regimen with a 1:1 ratio: "Moderate-intensity statin plus ezetimibe group" vs. "High-intensity statin monotherapy group".
In this study, the combination therapy strategy will utilize Pitavastatin 1-4 mg plus Ezetimibe 10 mg once daily or Atorvastatin 10-20 mg plus Ezetimibe 10 mg once daily. The monotherapy strategy will utilize Atorvastatin 40 mg once daily.
Study visits are scheduled at 4 weeks and at 6, 12, 18, 24, 30, and 36 months. The primary outcome is the composite of cardiovascular death, myocardial infarction, stroke, hospitalization for unstable angina, or coronary revascularization. The key secondary outcome is CKD progression defined as a ≥40% decline in eGFR confirmed on at least two consecutive measurements
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
- 19 Years 至 85 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age 19-85 years.
- •Chronic kidney disease stage III, IV, or V (CKD-EPI eGFR <60 / <30 / <15 mL/min/1.73 m² or on dialysis).
- •Established ASCVD, meeting at least one of the following:
- •Prior acute coronary syndrome (myocardial infarction or unstable angina).
- •Stable angina confirmed by imaging studies.
- •History of coronary revascularization (percutaneous coronary intervention or coronary artery bypass grafting).
- •Peripheral artery disease.
- •Ischemic stroke or transient ischemic attack.
排除标准
- •Baseline LDL cholesterol <55 mg/dL in the absence of statin therapy.
- •Acute liver disease or persistently unexplained serum AST/ALT ≥2 × the upper limit of normal.
- •Allergy or hypersensitivity to statins.
- •Life expectancy <1 year.
- •Expected inability to complete at least 1 year of follow-up.
- •Inability to read or understand the informed consent form.
研究组 & 干预措施
Moderate-intensity statin and ezetimibe combination therapy
Participants will receive moderate-intensity statin plus ezetimibe (pitavastatin 1-4 mg + ezetimibe 10 mg once daily or atorvastatin 10-20 mg + ezetimibe 10 mg once daily), with 36-month follow-up.
干预措施: Moderate-intensity statin and ezetimibe combination therapy (Drug)
High-intensity statin monotherapy
Participants will receive high-intensity statin monotherapy (atorvastatin 40 mg once daily), with 36-month follow-up.
干预措施: High-intensity statin monotherapy (Drug)
结局指标
主要结局
Major adverse cardiovascular events
时间窗: 3 years
Composite of cardiovascular death, myocardial infarction, stroke, hospitalization for unstable angina, or coronary revascularization.
次要结局
- CKD progression(3 years)
- Cardiovascular death.(3 years)
- Myocardial infarction.(3 years)
- Stroke.(3 years)
- Hospitalization for unstable angina.(3 years)
- Coronary revascularization.(3 years)
- Composite of cardiovascular death, myocardial infarction, and stroke.(3 years)
- Composite of cardiovascular death, myocardial infarction, stroke, and hospitalization for unstable angina(3 years)
- Composite of cardiovascular death, myocardial infarction, stroke, and coronary revascularization.(3 years)
- Composite of all-cause death, myocardial infarction, stroke, hospitalization for unstable angina, and coronary revascularization.(3 years)
- Proportion of participants achieving the LDL-C <70 mg/dL in each group.(3 years)
- Proportion of participants achieving LDL-C <55 mg/dL in each group.(3 years)
- Proportion of participants crossing over to the non-assigned treatment group in each group.(3 years)
- New-onset diabetes mellitus.(3 years)
- New-onset diabetes mellitus requiring initiation of antidiabetic medication.(3 years)
- Worsening glycemic control.(3 years)
- Marked decline in kidney function(3 years)
- Initiation of dialysis or kidney transplantation.(3 years)
- Statin-associated muscle symptoms requiring a change in regimen or dose.(3 years)
- Rhabdomyolysis.(3 years)
- Elevated creatine phosphokinase (CK >4 × the upper limit of normal)(3 years)
- Cancer diagnosis(3 years)
- Cataract surgery.(3 years)
- Hemorrhagic stroke.(3 years)
- Major bleeding (BARC type 2, 3, or 5 bleeding), assessed among participants who underwent percutaneous coronary intervention with new stent implantation at study enrollment.(3 years)
- Elevated liver enzymes (AST and/or ALT ≥3 × the upper limit of normal)(3 years)