Changes in Plaque Characteristics After Short-term Statin Therapy as Assessed With Coronary CT
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 发起方
- 入组人数
- 140
- 试验地点
- 1
- 主要终点
- Change in non-calcified plaque volume during a 3-month follow-up period.
研究概览
简要总结
INTENSE Trial is a prospective, double-blind, randomized, placebo-controlled, single-center study with two arms (40 mg intensified statin therapy vs matching placebo for rosuvastatin) among statin-naive patients referred to coronary CT angiography due to stable chest pain, followed for 24 months by using a photon-counting detector CT (PCD-CT).
INTENSE Trial aims 1) to assess the effect of short-term intensified statin therapy on coronary anatomy and physiology using PCD-CT and 2) to determine the impact of short-term, intensified statin therapy on coronary plaque morphology and hemodynamics to identify statin responder and non-responder patients in addition to testing the hypothesis of "plaque memory" after the 24-month follow-up period.
详细描述
The extent to which short-term intensified statin treatment may modulate plaque lipid content, alter plaque structure, and change flow physiology as assessed by non-invasive imaging remains unknown. Furthermore, no data is available regarding the effects of short-term intensified statin therapy on coronary plaques as assessed by Photon-Counting Detector CT (PCD-CT). In addition, no data is available regarding the long-term effects of short, intensified statin therapy on plaque morphology (i.e., plaque memory). Therefore, in this randomized, controlled, prospective, double-blind, single-center clinical trial, we aimed 1) to assess the effect of short-term intensified statin therapy on coronary anatomy and physiology using PCD-CT and 2) to assess the effect of short, intensified statin treatment on long term changes in plaque characteristics. In other words, to test our "plaque memory" hypothesis. Our analyses include a detailed evaluation of plaques by combining anatomic (quantitative and qualitative plaque assessment, radiomics) and hemodynamic (Fractional Flow Reserve-CT, FFR-CT) information.
In this randomized, controlled, prospective double-blinded single-center clinical trial, we aim to enroll statin naive patients (patients with no previous or current statin treatment) who underwent PCD-CT (NAEOTOM Alpha, Siemens Healthineers, Erlangen, Germany) exam due to stable chest pain and suspected coronary artery disease (CAD) at the Medical Imaging Centre of Semmelweis University, Budapest, Hungary. Coronary CT Angiography (Coronary CTA) examinations will be performed in accordance with the current guidelines of the Society of Cardiovascular Computed Tomography.
We will enroll patients aged 30-65 years, with at least one partially calcified or non-calcified plaque and with negative FFR-CT (FFR-CT>0.75 distal to stenosis).
Patients with contraindications to coronary CTA and patients post-revascularisation will be excluded from the study. Additional exclusion criteria: patients receiving lipid-lowering therapy before coronary CTA exam; alanine aminotransferase (ALT) levels >3× upper limit of normal (ULN); unexplained serum creatine kinase (CK) level >3× ULN; serum creatinine >2 mg/dL (177 umol/l), elevated low-density lipoprotein (LDL) level >5 mmol/L.
Patients will be randomized into 'high-dose statin' and 'placebo' groups, considering the age and sex of the patients to achieve equal representation of age groups and genders in both arms. Based on the sample size calculation, 70-70 patients must be randomized into each group. For those who will be randomized to the 'high-dose statin' group, 40 mg rosuvastatin therapy will be initiated. For those who will be randomized to the 'placebo' group, a placebo therapy will be started with medications that look the same as 40 mg rosuvastatin pills.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 45 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •patients referred for coronary computed tomography angiography (CTA)
- •females aged 45-75 years and males aged 40-75 years
- •presence of at least mild coronary atherosclerosis (luminal stenosis >25%, with at least one partially calcified or non-calcified plaque)
- •statin-naive patients
- •ability to understand and provide written informed consent
- •FFR-CT value ≥0.75, indicating the absence of hemodynamically significant stenosis
排除标准
- •contraindications to coronary CTA
- •current or prior treatment with statins or other lipid-lowering agents (e.g., ezetimibe)
- •age below 45 years in females or below 40 years in males
- •age above 75 years in both sexes
- •pregnancy or breastfeeding
- •type 1 or type 2 diabetes mellitus
- •history of coronary stent implantation or coronary artery bypass grafting
- •history of myocardial infarction
- •≥70% luminal stenosis in the proximal left anterior descending artery (LAD), or ≥50% stenosis in the left main (LM) coronary artery
- •FFR-CT value <0.75 in any coronary artery
- •elevated serum alanine aminotransferase (ALT) levels (>3× the upper limit of normal)
- •elevated serum creatine kinase (CK) levels (>3× the upper limit of normal)
- •LDL cholesterol level >5 mmol/L
- •renal failure or significantly impaired renal function (eGFR <30 mL/min/1.73 m²)
- •ongoing oncological treatment
- •active liver disease
- •known hypersensitivity to any excipients of the investigational product
- •concomitant treatment with the combination of sofosbuvir/velpatasvir/voxilaprevir
- •concomitant treatment with cyclosporine
- •women of childbearing potential not using adequate contraception
- •presence of myopathy
研究组 & 干预措施
Intensified Statin Arm
Participants will receive one capsule (40 mg of rosuvastatin), taken once daily for 3 months, orally with or without food. After the 3-month visit, the dose will be reduced to a dose per standard of care.
干预措施: Rosuvastatin 40mg (Drug)
Intensified Statin Arm
Participants will receive one capsule (40 mg of rosuvastatin), taken once daily for 3 months, orally with or without food. After the 3-month visit, the dose will be reduced to a dose per standard of care.
干预措施: Coronary Computed Tomography Angiography (Coronary CTA) (Diagnostic Test)
Intensified Statin Arm
Participants will receive one capsule (40 mg of rosuvastatin), taken once daily for 3 months, orally with or without food. After the 3-month visit, the dose will be reduced to a dose per standard of care.
干预措施: Blood test (Diagnostic Test)
Placebo Arm
Participants will receive one capsule (a placebo for rosuvastatin), taken once daily for 3 months, orally with or without food. After the 3-month visit standard rosuvastatin therapy will be initiated.
干预措施: Placebo (Drug)
Placebo Arm
Participants will receive one capsule (a placebo for rosuvastatin), taken once daily for 3 months, orally with or without food. After the 3-month visit standard rosuvastatin therapy will be initiated.
干预措施: Coronary Computed Tomography Angiography (Coronary CTA) (Diagnostic Test)
Placebo Arm
Participants will receive one capsule (a placebo for rosuvastatin), taken once daily for 3 months, orally with or without food. After the 3-month visit standard rosuvastatin therapy will be initiated.
干预措施: Blood test (Diagnostic Test)
结局指标
主要结局
Change in non-calcified plaque volume during a 3-month follow-up period.
时间窗: 12 weeks
Expressed as absolute change and as a percentage of baseline.
Change in non-calcified plaque volume during a 3-month follow-up period.
时间窗: 12 weeks
Expressed as absolute change and as a percentage of baseline.
次要结局
- Change in the prevalence of high-risk plaque features during a 3-month follow-up period.(12 weeks)
- Change in the prevalence of high-risk plaque features during a 24-month follow-up period.(24 months)
- Change in low attenuation non-calcified plaque volume during a 3-month follow-up period.(12 weeks)
- Change in low attenuation non-calcified plaque volume during a 24-month follow-up period.(24 months)
- Change in total plaque volume during a 24-month follow-up period.(24 months)
- Change in total plaque volume between 3- and 24-month follow-up period.(21 months)
- Change in non-calcified plaque volume between 3- and 24-month follow-up period.(21 months)
- Change in non-calcified plaque volume during a 24-month follow-up period.(24 months)
- Change in plaque composition during a 3-month follow-up period.(12 weeks)
- Change in plaque composition during a 24-month follow-up period.(24 months)
- Change in per-vessel fractional flow reserve [FFRCT] during a 3-month follow-up period.(12 weeks)
- Change in per-vessel fractional flow reserve [FFRCT] during a 24-month follow-up period.(24 months)
- Change in radiomic features during a 24-month follow-up period.(24 months)
- Change in radiomic features during a 3-month follow-up period.(12 weeks)
- Prevalence of major adverse cardiac event(From inclusion up to a maximum follow-up period of 4 years)
- Prevalence of clinical adverse event(From inclusion up to a maximum follow-up period of 4 years)
- Change in total plaque volume between 3- and 24-month follow-up period.(21 months)
- Change in total plaque volume at 3-month follow-up period.(12 weeks)
- Change in plaque composition during a 3-month follow-up period.(12 weeks)
- Change in low attenuation non-calcified plaque volume during a 3-month follow-up period.(12 weeks)
- Change in low attenuation non-calcified plaque volume during a 24-month follow-up period.(24 months)
- Change in total plaque volume during a 24-month follow-up period.(24 months)
- Change in non-calcified plaque volume between 3- and 24-month follow-up period.(21 months)
- Change in non-calcified plaque volume during a 24-month follow-up period.(24 months)
- Change in plaque composition during a 24-month follow-up period.(24 months)
- Change in per-vessel fractional flow reserve [FFRCT] during a 3-month follow-up period.(12 weeks)
- Change in per-vessel fractional flow reserve [FFRCT] during a 24-month follow-up period.(24 months)
- Change in the prevalence of high-risk plaque features during a 3-month follow-up period.(12 weeks)
- Change in the prevalence of high-risk plaque features during a 24-month follow-up period.(24 months)
- Change in radiomic features during a 3-month follow-up period.(12 weeks)
- Change in radiomic features during a 24-month follow-up period.(24 months)
- Prevalence of major adverse cardiac event(From inclusion up to a maximum follow-up period of 4 years)
- Prevalence of clinical adverse event(From inclusion up to a maximum follow-up period of 4 years)
- Reproducibility of quantitative plaque assessment(12 weeks)
研究者
Prof. Maurovich-Horvat Pál
Head of Clinic for Medical Imaging
Semmelweis University