A Pilot Study to Investigate Platelet Reactivity in Patients With Elevated Lipoprotein(a) and Its Response to Antiplatelet Therapy Randomised, Open-Label, Mechanistic Pilot Study With A Crossover Design
试验速览
- 阶段
- 不适用
- 状态
- 尚未招募
- 发起方
- 入组人数
- 60
- 试验地点
- 1
- 主要终点
- Change in collagen-induced platelet aggregation after aspirin versus clopidogrel treatment
研究概览
简要总结
The Lp(a)-PLAT Study is designed to close a critical evidence gap in cardiovascular prevention for the roughly 20% of the population who carry genetically determined elevations in lipoprotein(a) - a recognised pro-thrombotic and pro-atherosclerotic risk factor. Its objective is to delineate the pro-thrombotic platelet phenotype driven by high Lp(a) levels and to evaluate, through pharmacodynamic comparison, how two standard-of-care antiplatelet strategies - clopidogrel, a P2Y12 ADP-receptor inhibitor, and aspirin, a COX-1 inhibitor - differ in their capacity to attenuate this platelet hyperreactivity.
This study will provide the first head-to-head mechanistic comparison of clopidogrel versus aspirin on platelet reactivity in patients with elevated plasma levels of Lp(a).
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Prevention
- 盲法
- Single (Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Age ≥ 18 years at the time of informed consent.
- •Ability to provide written informed consent in accordance with Swiss Human Research Act (HRA) and ICH-GCP.
- •Documented plasma lipoprotein(a) [Lp(a)] concentration:
- •High Lp(a) cohort: ≥ 125 nmol/L (approximately ≥ 75th percentile) Low Lp(a) comparator cohort (if applicable): < 25-30 nmol/L
- •Clinically stable at the time of inclusion, with no acute cardiovascular event within the previous 3 months.
- •Willingness and ability to comply with all study procedures, including blood sampling and study medication intake.
- •For women of childbearing potential: willingness to use adequate contraception during the study period (if applicable according to local ethics requirements).
排除标准
- •Cardiovascular and bleeding-related conditions Active bleeding or known bleeding disorder. History of hemorrhagic stroke or intracranial hemorrhage. High risk of bleeding as judged by the investigator. Platelet count < 100 × 10⁹/L at screening. Known platelet function disorder.
- •Contraindications to study medications Known hypersensitivity or contraindication to aspirin (acetylsalicylic acid) or clopidogrel.
- •History of aspirin-induced asthma, severe NSAID intolerance, or anaphylactic reaction to salicylates.
- •Active peptic ulcer disease or clinically significant gastrointestinal bleeding within the past 6 months.
- •- Concomitant medications and interference with platelet function Current use of dual antiplatelet therapy (DAPT), oral anticoagulants (e.g., DOACs, vitamin K antagonists), or other potent antithrombotic agents that cannot be safely interrupted.
- •Use of non-steroidal anti-inflammatory drugs (NSAIDs) within 7 days prior to study entry (unless discontinued per protocol).
- •Use of P2Y12 inhibitors or aspirin within an insufficient washout period. - Clinical conditions Severe hepatic impairment (ALT/AST > 3× ULN) or severe renal impairment (eGFR < 30 mL/min/1.73 m²).
- •Active malignancy requiring systemic chemotherapy. Known hematologic disorder affecting platelet function or coagulation. Acute infection or inflammatory condition likely to affect platelet function.
- •- Other exclusions Pregnancy or breastfeeding. Participation in another interventional clinical trial within the last 30 days or 5 half-lives of the investigational product, whichever is longer.
- •Any condition that, in the opinion of the investigator, would interfere with study participation, compliance, or interpretation of results.
结局指标
主要结局
Change in collagen-induced platelet aggregation after aspirin versus clopidogrel treatment
时间窗: Baseline and Day 14 of each treatment period (up to 42 days)
Within-participant change from baseline in collagen-induced platelet aggregation measured by light transmission aggregometry (LTA) after 14 days of aspirin 100 mg once daily compared with 14 days of clopidogrel 75 mg once daily in the randomized crossover design.
Change in soluble platelet activation biomarkers after aspirin versus clopidogrel treatment
时间窗: Baseline and Day 14 of each treatment period (up to 42 days)
Within-participant change from baseline in soluble platelet activation biomarkers (including soluble P-selectin/CD62P, soluble CD40 ligand \[sCD40L\], platelet factor 4 \[PF4\], and related biomarkers) following 14 days of aspirin 100 mg once daily compared with 14 days of clopidogrel 75 mg once daily.
次要结局
- Agonist-specific platelet aggregation(Baseline and Day 14 of each treatment period (up to 42 days))
- Platelet surface activation markers(Baseline and Day 14 of each treatment period (up to 42 days))
- Biochemical verification of aspirin pharmacodynamic effect(Day 14 of the aspirin treatment period)
- Biochemical verification of clopidogrel pharmacodynamic effect(Day 14 of the clopidogrel treatment period)
- Association between plasma lipoprotein(a) concentration and platelet function(Baseline and Day 14 of each treatment period (up to 42 days))
- Baseline comparison of platelet reactivity between participants with high and low lipoprotein(a)(Baseline (Day 0))
- Plasma proteomic profile associated with lipoprotein(a) and antiplatelet therapy (Exploratory)(Baseline and Day 14 of each treatment period (up to 42 days))
研究者
François MACH
Professor, MD
University Hospital, Geneva