A Phase IV, Double-Blind, Placebo-Controlled, Multi-Center Trial To Study The Effects Of Evolocumab In Stage IV-V Chronic Kidney Disease: The Cardiovascular and Lipid-Lowering Effects Of Evolocumab In Advanced Chronic Kidney Disease Trial
试验速览
- 阶段
- 4 期
- 状态
- 撤回
- 试验地点
- 2
- 主要终点
- Absolute change in LDL cholesterol concentration
研究概览
简要总结
110 individuals with stage 4-5 Chronic Kidney Disease (CKD) will be randomized to 1-year of blinded Evolocumab or placebo. Subjects will undergo evaluation of circulating lipids at baseline and end of study. A substudy including 50 subjects will assess myocardial rest and stress positron emission tomography (PET) at baseline and at 1-year.
详细描述
The purpose of this study is to evaluate the effect of evolocumab (Repatha®)-a Food and Drug Administration (FDA)-approved biological drug that has been shown to reduce LDL cholesterol (bad cholesterol) Early data show that the beneftis of evolocumab may be increased as kidney function declines. This trial is therefore designed to provide additional evidence regarding the safety and cholesterol-lowering effects of evolocumab compared with placebo, a pill that has no therapeutic effect, in advanced CKD patients.
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
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 40 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •CKD Stage 4-5 defined as
- •eGFR ≤30 mL/min/1.73m2 on screening lab OR
- •Treatment with maintenance hemodialysis for at least 30 days prior to screening
- •LDL ≥70 mg/dL and
- •Treatment with maximal tolerated doses of a statin OR
- •Statin intolerance defined as any history of intolerance or allergy to ≥1 statin
- •Age 40-80 years
- •Individuals ≤60 years old are required to have ≥1 of the following cardiovascular risk factors:
- •History of CV disease
- •History of peripheral vascular disease
- •Baseline LDL ≥160 mg/dL
- •Macroalbuminuria (albumin to creatinine ratio ≥300 mg/g on spot sample)
排除标准
- •Age >80 years
- •Expected survival < 1 year
- •Transplant expected within < 1 year
- •Active liver disease (history of cirrhosis, ALT or AST > 2x ULN)
- •CPK > 5x ULN at screening
- •Malignancy within 5 years except for non-melanoma skin cancers, cervical in-situ carcinoma, breast ductal carcinoma in situ, or stage 1 prostate carcinoma
- •Subject has received drugs that are strong inhibitors of cytochrome P-450 3A4 within 1 month prior to randomization or is likely to require such treatment during the study period
- •Currently enrolled in another interventional study
- •Female subject who has not used at least (1) effective method of birth control for at least 1 month prior to screening or (2) is not willing to use such a method during treatment and for an additional 15 weeks after the end of treatment, unless the subject is sterilized or postmenopausal.
- •Effective measures of birth control include surgical sterilization, barrier methods, hormonal contraceptives and intrauterine devices.
- •Pregnant or breast-feeding subjects
- •Known sensitivity or intolerance to study medications
- •The following additional criteria will be utilized to exclude individuals from participating in the PET substudy:
- •Severe asthma or obstructive lung disease defined by
- •Hospitalization for asthma or obstructive lung disease within 8 weeks
- •Use of oral steroids for lung disease within 8 weeks
- •Chronic oxygen therapy
- •Use of rescue inhalers ≥three times weekly in the previous 4 weeks
- •History of seizures
- •Second or third-degree AV block, unless a functioning pacemaker is present
- •Sinus node dysfunction unless a functioning pacemaker is present
研究组 & 干预措施
Study Drug Group
Participants who will receive a shot of the Evolocumab at Visit 3 and self-administer the rest of the shots at visit 4-7.
干预措施: Evolocumab (Drug)
Placebo group
Participants who will receive a Placebo shot at Visit 3 and self-administer the rest of the shots at visit 4-7.
干预措施: Placebo (Other)
结局指标
主要结局
Absolute change in LDL cholesterol concentration
时间窗: Baseline, Week 52
The primary endpoint is selected to evaluate the key pharmacologic mechanism underlying Evolocumab's cardiovascular benefits. This will be analyzed with Lipid parameters.
次要结局
- Number of Serious Adverse Events (SAEs)(Baseline, Week 52)
- Change in coronary flow reserve (CFR)(Baseline, Week 52)