Polygenic Risk-based Detection of Subclinical Coronary Atherosclerosis and Intervention With Statin and Colchicine
试验速览
- 阶段
- 4 期
- 状态
- 进行中（未招募）
- 入组人数
- 200
- 试验地点
- 1
- 主要终点
- Change in total non-calcified plaque volume from baseline to one year
研究概览
简要总结
The goal of this double-blind randomized controlled trial is to determine how treatment with high intensity statin, low-dose colchicine, and their combination modulates progression and composition of coronary atherosclerosis in individuals with high polygenic risk for coronary artery disease.
详细描述
The main question PROACT 2 aims to answer is whether and how single or dual targeting of cholesterol-lowering and inflammation modulates coronary plaque in individuals with high polygenic risk and subclinical coronary atherosclerosis.
This is a double-blind randomized controlled trial of 200 individuals with high polygenic risk for coronary artery disease and subclinical plaque on coronary computed tomography angiography. Participants will be randomized into four equal treatment groups: group A receiving a placebo daily, group B receiving rosuvastatin 20mg daily, group C receiving colchicine 0.6mg daily, and group D receiving both rosuvastatin 20mg daily and colchicine 0.6mg daily. The primary outcome is change in total non-calcified plaque volume on coronary computed tomography angiography from baseline to one year. Multiple secondary plaque imaging and biomarker outcomes will be explored in this pilot mechanistic trial.
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
- 40 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Males and females between 40 and 75 years of age capable and willing to provide informed consent
- •Participant has high CAD PRS as defined on a clinical test
- •Participant with subclinical atherosclerosis defined as plaque visible on CCTA and causing <70% luminal stenosis
排除标准
- •Participant with a history of cardiovascular disease, defined by a diagnosis of coronary artery disease, peripheral artery disease, or cerebrovascular disease
- •Participant with a history of Liver disease (cirrhosis, active hepatitis, or severe hepatic disease) or any of the following recent lab results and determined to be non-transient: alanine aminotransferase greater than 3 times the upper limit of normal or total bilirubin greater than 2 times the upper limit of normal (unless due to Gilbert syndrome)
- •Participant with estimated glomerular filtration rate <60 mL/min/1.73 m2 or creatinine greater than 2 times the upper limit of normal
- •Patient with history of an allergic reaction or significant sensitivity to iodinated contrast, colchicine, or statins
- •Patient currently taking LDL cholesterol lowering or anti- inflammatory medications including colchicine
- •Participants requiring regular drugs known to be potent CY2P inhibitors (eg. ketoconazole, clarithromycin)
- •Female patient who is pregnant, or breast-feeding or is considering becoming pregnant during the study
- •Participant with BMI ≥ 40 kg/m2
- •Participant unable to provide informed consent
- •Participant unable to hold breath for 10 seconds
研究组 & 干预措施
Group C
Participants will receive colchicine 0.6mg daily and placebo daily
干预措施: Placebo (Drug)
Group B
Participants will receive rosuvastatin 20mg daily and placebo daily
干预措施: Rosuvastatin (Drug)
Group A
Participants will receive placebo daily
干预措施: Placebo (Drug)
Group B
Participants will receive rosuvastatin 20mg daily and placebo daily
干预措施: Placebo (Drug)
Group C
Participants will receive colchicine 0.6mg daily and placebo daily
干预措施: Colchicine (Drug)
Group D
Participants will receive rosuvastatin 20mg daily and colchicine 0.6mg daily
干预措施: Rosuvastatin (Drug)
Group D
Participants will receive rosuvastatin 20mg daily and colchicine 0.6mg daily
干预措施: Colchicine (Drug)
结局指标
主要结局
Change in total non-calcified plaque volume from baseline to one year
时间窗: 1 year
The primary outcome of this study is the change in total non-calcified plaque volume between the two groups from baseline to one year. This outcome will be measured using coronary computed tomography angiography (CCTA) and reported in cubic millimeters (mm³). The comparison of the changes in non-calcified plaque volume will help assess the effectiveness of the intervention on plaque progression and composition.
次要结局
- Change in number of high-risk features from baseline to one year(1 year)
- Change in maximal luminal stenosis from baseline to one year(1 year)
- Change in calcium score from baseline to one year(1 year)
- Change in fat attenuation index from baseline to one year(1 year)
- Progression in non-calcified plaque volume from baseline to one year(1 year)
- Change in total plaque volumes from baseline to one year(1 year)
- Change in low-density lipoprotein cholesterol (LDL-C) from baseline to one year(1 year)
- Change in C-reactive protein (CRP) from baseline to one year(1 year)
- Change in Interleukin-6 and Interleukin-1 beta (IL-1ß) from baseline to one year(1 year)
研究者
Akl C. Fahed, MD, MPH
Interventional Cardiologist
Massachusetts General Hospital