Phase IV Study for Efficacy and Safety of Evolocumab Added to Ezetimibe (Standard of Care) in High Cardiovascular Risk Haemodialized Statin Intolerant Patients With Hypercholesterolemia
试验速览
- 阶段
- 4 期
- 发起方
- 入组人数
- 50
- 试验地点
- 1
- 主要终点
- LDL cholesterol reduction dichotomic
研究概览
简要总结
Evolocumab is a monoclonal antibody that inhibits proprotein convertase subtilisin-kexin type 9 (PCSK9) and lowers low-density lipoprotein (LDL) cholesterol, reducing in turn the risk of cardiovascular events. Whether evolcumab is effective in haemodialized patients is uncertain. The investigators will conduct a randomized, double-blind, placebo-controlled trial to assess the feasibility, safety, and LDL-C-lowering efficacy of evolocumab in high cardiovascular risk haemodialized statin intolerant patients with hypercholesterolemia. Patients will be randomly assigned to receive evolocumab (140 mg subcutaneous every 2 weeks + ezetimibe 10 mg per os daily) or matching placebo (subcutaneous every 2 weeks + ezetimibe 10 mg per os daily) for 24 weeks. The primary efficacy end point will be the reduction in LDL-C ≥ 20 mg/dL from baseline. The key secondary efficacy end points will be: the reduction of LDL-C from baseline at 4, 6 and 12 weeks; the reduction of HDL-C, non-HDL cholesterol and triglycerides from baseline at 24 weeks; the number of patients achieving LDL-C <70 mg/dL. Every adverse event (serious and non-serious) correlated to drug infusion will be recorded (safety end-point).
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
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- 未提供
排除标准
- •LDL-C <70 mg/dL
- •NYHA class III-IV heart failure or last known LVEF <30%
- •Uncontrolled serious cardiac arrhythmia, defined as recurrent and highly symptomatic VT, AF with rapid ventricular response, or SVT that are not controlled by medications, within 3 months prior to randomization Planned cardiac surgery or revascularization DM, including: Type 1 DMType 2 DM that is poorly controlled (HbA1c>8.5%) or newly diagnosed within 6 months before randomization; Laboratory evidence of DM during screening (fasting serum glucose ≥126 mg/dL [7.0 mmol/L] or HbA1c≥6.5%) without prior DM diagnosis
- •Uncontrolled hypertension, defined as sitting SBP >160mmHg or DBP>100 mm Hg
- •Use during the 6 months before LDL-C screening of red yeast rice, niacin >200 mg/d, prescription lipid-regulating drugs (eg, fibrates or derivatives) other than statins, ezetimibe, bile-acid sequestrants, stanols, or stanol esters
- •Use during the 12 months before LDL-C screening of a CETP inhibitor such as anacetrapib, dalcetrapib, or evacetrapib
- •Use during the 3 months before LDL-C screening of systemic cyclosporine, systemic steroids excluding HRT, vitamin A derivatives (excluding vitamin Ain a multivitamin), or retinol derivatives for the treatment of dermatologic conditions
- •Laboratory values at screening TSH < LLN or >1.5 × ULN; CK >3 × ULN; AST or ALT >2 × ULN
- •Known concurrent illness within 3 months
- •Infection
- •Major hematologic, renal, metabolic, GI, or endocrine dysfunction in the judgment of the investigator
- •DVT or PE
- •Pregnancy, breastfeeding, or inadequate birth control in premenopausal female subjects
- •Previous treatment with evolocumab or any other anti-PCSK9 therapy
- •Inability to provide informed consent or to attend follow-up visits
- •Unreliability as a study participant based on judgment of investigator's knowledge of the subject (eg, alcohol or other drug abuse, inability or unwillingness to adhere to the protocol, psychosis)
- •Current enrollment in another investigational device or drug study or <30 d since ending another investigational device or drug study
研究组 & 干预措施
Evolocumab + Ezetimibe
Patients in this arm will receive subcutaneous evolocumab 140 mg every two weeks plus ezetimibe 10 mg per os daily for 24 weeks
干预措施: Evolocumab (Drug)
Evolocumab + Ezetimibe
Patients in this arm will receive subcutaneous evolocumab 140 mg every two weeks plus ezetimibe 10 mg per os daily for 24 weeks
干预措施: Ezetimibe (Drug)
Placebo + Ezetimibe
Patients in this arm will receive subcutaneous placebo every two weeks plus ezetimibe 10 mg per os daily for 24 weeks
干预措施: Placebo (Drug)
Placebo + Ezetimibe
Patients in this arm will receive subcutaneous placebo every two weeks plus ezetimibe 10 mg per os daily for 24 weeks
干预措施: Ezetimibe (Drug)
结局指标
主要结局
LDL cholesterol reduction dichotomic
时间窗: 24 weeks
change in LDL cholesterol levels ≥ 20 mg/dL from baseline
次要结局
- LDL cholesterol reduction time-points(4 weeks, 12 weeks, 24 weeks)
- HDL cholesterol reduction(24 weeks)
- non-HDL cholesterol reduction(24 weeks)
- Triglycerides reduction(24 weeks)
- LDL cholesterol target achieving(24 weeks)
研究者
Leonardo Calò, MD
Professor
Policlinico Casilino ASL RMB