Clinical Trial to Evaluate the Effect of Alirocumab on the Volume, Architecture and Composition of Atherosclerotic Plaque in Patients With Familial Hypercholesterolemia
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 发起方
- 入组人数
- 104
- 试验地点
- 1
- 主要终点
- Change in atherosclerotic plaque burden (%) assessed by coronary computed tomography
研究概览
简要总结
Low-level, open-label, multicenter clinical trial to evaluate the effect of alirocumab on the volume, architecture and composition of atherosclerotic plaque in patients with Familial hypercholesterolemia from the SAFEHEART Registry. ARCHITECT study
详细描述
DISEASE UNDER STUDY Heterozygous familial hypercholesterolemia (FH).
MAIN PURPOSE OF THE TEST The main objective is to evaluate the effect of alirocumab on the burden of coronary atherosclerosis, based on the change in the percentage of volume of atheroma (PVA) by quantifying the atheroma plaque and virtual histology in the entire coronary tree based on the Analysis of coronary CT angiography (CTA) in asymptomatic subjects with FH on optimized and stable treatment with the maximum tolerated doses of statins with or without other lipid-lowering treatments.
MAIN VALUATION VARIABLE The primary endpoint is the change in PVA, throughout the coronary tree, from baseline assessment (before initiation of alirocumab treatment) to 18 months after initiation of alirocumab treatment, based on CTA images analyzed by the QAngio CT software.
DESIGN Low-intervention, open-label, multicenter, phase IV clinical trial to evaluate the effect 18 months after initiation of alirocumab (Praluent®) on the volume, architecture, and composition of the coronary atheroma plaque in subjects with FH and without clinical cardiovascular disease followed in the SAFEHEART registry in optimized and stable treatment with maximum tolerated doses of statins with or without other lipid-lowering treatments under clinical practice conditions.
The study will be carried out in the internal medicine, lipid, endocrinology, and cardiology units of approximately 30 Spanish hospitals.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 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
- •Have voluntarily granted informed consent (preferably in writing or, failing that, orally before independent witnesses of the research team) before carrying out the specific procedures of the trial.
- •Patients of both sexes aged between 35 and 65 years.
- •Patients with a molecular diagnosis of heterozygous HF included in the Spanish SAFEHEART registry (http://safeheart.colesterolfamiliar.org/).
- •Asymptomatic patients.
- •Patients without a previous history of clinical cardiovascular events (acute myocardial infarction [AMI], stroke, coronary revascularization, etc.).
- •Patients on optimized and stable treatment with maximum tolerated doses of a statin with or without other lipid-lowering therapies, for at least 3 months, with inadequate control, defined by a LDL-C level> 100 mg / dL.
- •Availability of a coronary CTA performed in the 3 months prior to the baseline visit. If a coronary CTA is not available, this test will be performed during the selection period.
- •ATC of at least 64 cuts performed in a center with sufficient experience (more than 100 ACTs per year).
- •Patients with a PVA> 30% in the baseline coronary CTA, performed in the last 3 months before the baseline visit.
- •Patients in whom treatment with alirocumab 150 mg / mL is indicated, according to the characteristics of the patient and the Praluent® technical data sheet.
排除标准
- •Class> II heart failure according to the functional classification of the NYHA scale (New York Heart Association).
- •Heart rate different from normal sinus rhythm (regular HR between 60-100 bpm).
- •Previous history of AMI, angina, peripheral arterial thrombosis, stroke or transient ischemic attack (TIA).
- •Uncontrolled hypertension defined as a resting systolic blood pressure value> 180 mmHg at the baseline visit.
- •Fasting triglyceride levels> 250 mg / dl at baseline visit.
- •Type 1 diabetes or insufficiently controlled type 2 diabetes (HbA1> 9%).
- •Personal or family history of inherited muscle disorders.
- •Known thyroid disease or thyroid replacement therapy.
- •Glomerular filtration rate <60 ml / min / 1.73 m2 at baseline visit.
- •Elevated ALT and / or AST levels (> 3 times the ULN at the baseline visit).
- •Elevated creatinine kinase levels (> 3 times ULN at baseline).
- •Patients who have previously received iPCSK9, CETP (cholesterol ester transport protein) inhibitors, mipomersen and / or lomitapide.
- •Patients with statin intolerance.
- •Active cancer or previous history of cancer.
- •Clinically relevant active infection or clinically significant hematologic, renal, metabolic, gastrointestinal, or endocrine dysfunction.
- •Availability of a baseline coronary ACT that does not meet the technical requirements for the images to be adequately processed using the QAngio CT software.
- •Patient being treated with any investigational drug / product or participating in a clinical trial using an investigational product, with the exception of studies in which the study treatment has been completed more than 6 months ago.
- •Pregnant or breast-feeding women, and sexually active women of childbearing potential who are unwilling to use an adequate contraceptive method (such as oral contraceptives, intrauterine device, or barrier method of contraception along with spermicide or surgical sterilization) during the study. Women of childbearing age are defined as those women who have not undergone permanent infertility procedures or who have been amenorrheic for less than 12 months.
研究组 & 干预措施
Alirocumab
Every patient enrolled witll receive treatment witl Alirocumab
干预措施: Alirocumab (Drug)
结局指标
主要结局
Change in atherosclerotic plaque burden (%) assessed by coronary computed tomography
时间窗: 18 months
change in plaque burden assessed by coronary computed tomography at enrollemnt and at follow-up. Coronary plaque burden and its cgaracteristics will be analysed ant enrollment and at the end of the follow-up
次要结局
- Changue in plaque volume (mm3) assessed by coronary computed tomography(18 months)