Lipid Lowering Therapy for Atherosclerotic Disease in Melanoma Patients Receiving Immune Checkpoint Inhibitors
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 40
- 试验地点
- 1
- 主要终点
- Mean change in LDL-C from baseline to 12 months
研究概览
简要总结
Immune checkpoint inhibitors (ICIs) are a class of medications that are now standard in the treatment of melanoma. These are standard therapy for melanoma, but long-term side effects on disease in the heart arteries is poorly understood. In this study, melanoma patients receiving ICIs for the first time will undergo a coronary computed tomography angiography (CCTA) scan. CCTA results will be analyzed by the FDA-approved Cleerly TM image analysis pipeline. Patients with disease in their heart arteries will be randomized to usual care or aggressive lipid lowering therapy. Those in the aggressive lipid lowering therapy arm will be seen by a cardiologist and placed on standard lipid lowering medications with a goal of achieving an LDL-C ≤ 55mg/dL. Follow-up CCTA scans will occur at 12-month and 24-month timepoints. The primary outcome of interest will be differences in LDL-C levels between the two arms at the 12-month timepoint. The secondary outcome of interest will be the differences in total plaque volume between the two arms at the 12-month timepoint.
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
- None
入排标准
- 年龄范围
- 55 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Provision to sign and date the consent form.
- •Stated willingness to comply with all study procedures and be available for the duration of the study.
- •Be a male aged ≥55 years or a female aged ≥65 years.
- •For those able to bear children, documentation of menopausal status via approximate last menstrual period or hysterectomy due to contraindication of pregnancy for the CCTA procedure.
- •Have a melanoma diagnosis without prior ICI use and planning to start on ICI therapy (PD-1, PD-L1, CTLA-4, LAG3) as standard of care for their cancer.
- •Plaque stage ≥ 1 on screening CCTA.
排除标准
- •Any prior major cardiovascular event, defined as myocardial infarction, stroke, coronary revascularization, or other major cardiovascular event determined to be significant by the principal investigator.
- •Meeting any of the standard CCTA contraindications listed below:
- •Allergy to iodinated contrast or history of contrast-induced nephropathy
- •Renal insufficiency (eGFR < 45 mL/min/1.73 m2 by the Chronic Kidney Disease Epidemiology Collaboration (CKD EPI) or Modification of Diet in Renal Disease (MDRD) equation). A current eGFR value (collected/calculated within 3 months from screening visit) is required at baseline.
- •Active arrhythmia (atrial fibrillation, atrial flutter, frequent premature atrial, or ventricular contractions) with poorly controlled rate (i.e., > 80 beats per minute). EKG must be performed within 1 year of screening visit.
- •Hemodynamic instability
- •Weight > 400 lbs. (181 kg) or above manufacturer-recommended limit for scanner and table, whichever is lower
- •Thyroid cancer in the previous five (5) years or planned radioactive iodine treatment
- •Pregnancy
- •Inability to hold breath for > 10 seconds
- •Contraindication to dosing with beta blocker as needed or nitroglycerin prior to CCTA procedure
- •Inability to cooperate with scan acquisition and/or breath-hold instructions
- •Any other factor that, in the opinion of the investigator, would increase participant risk or increase the chance of an uninterpretable CCTA
- •If a patient's fast LDL-C is > 190 mg/dL, this is consistent with underlying familial hypercholesterolemia, and they will not be eligible for the study.
- •If a patient's CCTA demonstrates previously undiagnosed obstructive coronary disease, they will not be eligible for the study. Obstructive disease will be defined as >50% obstruction in the left main coronary artery, or >70% obstruction elsewhere in the coronary tree.
研究组 & 干预措施
Active Comparator: Usual Care
Active Comparator: Usual Care: 12- and 24-month follow-up CCTA with plaque staging, lipid panel
Aggressive Lipid Lowering Therapy
Participants in the 'aggressive lipid lowering therapy' arm will receive guideline-directed lipid lowering therapy (statins and/or PCSK9 inhibitors) managed by a cardiologist. Dosing adjustments will be guided by individual patient response and standard-of-care practices, with the goal of achieving LDL-C ≤55 mg/dL.
干预措施: Statins (atorvastatin, rosuvastatin, simvastatin, or pravastatin), +/- ezetimibe, +/- PCSK9 inhibitor (alirocumab, evolocumab, inclisiran) (Drug)
结局指标
主要结局
Mean change in LDL-C from baseline to 12 months
时间窗: Baseline to 12 months
Each participant will have LDL-C measured prior to randomization and at the 12-month timepoint. The mean change in LDL-C (mg/dL) from baseline to 12 months will be calculated for each participant. The mean change will be compared between the aggressive lipid-lowering therapy arm and the usual care arm.
次要结局
- Change in Total Plaque Volume from Baseline to 12 months(12 months)
- Major adverse cardiovascular events at 12 months(12 months)
- Change in Calcified Plaque Volume from Baseline to 12 Months(12 months)
- Change in Size of the Largest Plaque from Baseline to 12 Months(12 months)