Vascular Toxicities of Immune ChecKpoint Inhibitors : From Bed to Benchside
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 39
- 试验地点
- 2
- 主要终点
- Endothelial dysfunction
研究概览
简要总结
Immune checkpoint inhibitors (ICIs) are largely prescribed in a growing number of cancer diseases and at earlier stages (non metastatic cancer). Among immune-related adverse events, (iRAEs), the incidence of major cardiovascular events due to atherosclerosis reaches 13% at one year in patients at high risk. To the best of our knowledge, the mechanisms of this acceleration of atherosclerosis have not been studied to this date.
The VICKI study aims at furthering our knowledge on the mechanisms of atherosclerotic plaque instability by means of a prospective single-centre pilot study, by comparing:
- surrogate markers of clinical vasculo-toxicity with arterial Doppler (flow mediated reserve) as defined by the International Cardio-Oncology Society;
- circulating biomarkers
Before and after receiving ICIs for solid cancer treatment.
详细描述
Context. Immune checkpoint inhibitors (ICIs) are largely prescribed in a growing number of cancer diseases and at earlier stages (non metastatic cancer). Among immune-related adverse events, (iRAEs), the incidence of major cardiovascular events due to atherosclerosis reaches 13% at one year in patients at high risk. To the best of our knowledge, the mechanisms of this acceleration of atherosclerosis have not been studied to this date.
Endothelial dysfunction is a predictor of the development of atherosclerotic plaque and events related to erosion or rupture. Endothelial dysfunction correlates well with the increase of circulating microparticles in various populations. The increase of circulating microparticles is also associated with major cardiovascular events.
The International society of Cardio-Oncology (IC-OS) recently published a definition for subclinical vascular toxicities due to ICIs. It includes non-invasive imaging methods readily available at the bedside (Herrmann et al. European Heart Journal 2022), largely replicated in the recent European Society of Cardiology (ESC) guidelines 2022. It includes the decrease of flow mediated reserve <7% or hyperhemia index <2; or the decrease of any of these biomarkers > 50% from baseline.
Aims and Methods. The VICKI study aims at furthering our knowledge on the mechanisms of atherosclerotic plaque instability by means of a prospective single-centre pilot study, by comparing:
- surrogate markers of clinical vasculo-toxicity with arterial Doppler (flow mediated reserve, hyperhemia index, plaque volume) as defined by IC-OS;
- circulating microparticles; Before and after receiving ICIs for solid cancer treatment.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Basic Science
- 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
- •All patients scheduled for first ICI therapy at our institution;
- •Matched controls with cancer and no ICI therapy;
排除标准
- •Major cardiovascular event in the past 6 months;
- •Unable to provide informed consent;
- •History of ICI therapy
结局指标
主要结局
Endothelial dysfunction
时间窗: 6 weeks
Surrogate marker of endothelial dysfunction : Signifiant FMD variation on ICIs as defined by the International Cardio-Oncology Society
次要结局
- Correlation of blood biomarkers to endothelial dysfunction (surrogate marker: Flow Mediated Dilatation variation)(6 weeks)
- Major cardiovascular event (MACE)(6 months)