A Pilot Study to Investigate Platelet Reactivity in Patients With Elevated Lipoprotein(a) and Its Response to Antiplatelet Therapy

Официальное название

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

Обзор

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).

Вмешательства

• Препарат Aspirin
  Aspirin 100 mg administered orally once daily for 14 consecutive days during one treatment period of the randomized crossover study. Participants receive aspirin either during Period 1 or Period 2 depending on the randomized treatment sequence. A 14-day washout period separates the two treatment periods.
• Препарат Clopidogrel
  Clopidogrel 75 mg administered orally once daily for 14 consecutive days during one treatment period of the randomized crossover study. Participants receive clopidogrel either during Period 1 or Period 2 depending on the randomized treatment sequence. A 14-day washout period separates the two treatment periods.

Первичные конечные точки

• Change in collagen-induced platelet aggregation after aspirin versus clopidogrel treatment [Срок оценки: Baseline and Day 14 of each treatment period (up to 42 days)]
• Change in soluble platelet activation biomarkers after aspirin versus clopidogrel treatment [Срок оценки: Baseline and Day 14 of each treatment period (up to 42 days)]

Вторичные конечные точки (7)

• Agonist-specific platelet aggregation [Срок оценки: Baseline and Day 14 of each treatment period (up to 42 days)]
• Platelet surface activation markers [Срок оценки: Baseline and Day 14 of each treatment period (up to 42 days)]
• Biochemical verification of aspirin pharmacodynamic effect [Срок оценки: Day 14 of the aspirin treatment period]
• Biochemical verification of clopidogrel pharmacodynamic effect [Срок оценки: Day 14 of the clopidogrel treatment period]
• Association between plasma lipoprotein(a) concentration and platelet function [Срок оценки: 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) [Срок оценки: Baseline (Day 0)]
• Plasma proteomic profile associated with lipoprotein(a) and antiplatelet therapy (Exploratory) [Срок оценки: Baseline and Day 14 of each treatment period (up to 42 days)]

Критерии участия

Критерии включения

• 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).

Критерии исключения

• 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.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Да

Дизайн исследования

Распределение

Рандомизированное

Модель

Перекрёстный дизайн

Маскирование

Простое слепое

Основная цель

Профилактика

Центры проведения

Швейцария · 1 центр

• Hopitaux Universitaires de Genève — Geneva

Идентификаторы

NCT: NCT07720934 · 2026-01415

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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