Cardiovascular Prevention
Conditions
Keywords
Lipoprotein(a)
Brief summary
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).
Interventions
DRUGAspirin
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.
DRUGClopidogrel
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.
Sponsors
François MACH
University Hospital, Geneva
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
PREVENTION
Masking
SINGLE (Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
* 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).
Exclusion criteria
* 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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in collagen-induced platelet aggregation after aspirin versus clopidogrel treatment | 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 | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Agonist-specific platelet aggregation | Baseline and Day 14 of each treatment period (up to 42 days) | Change from baseline in platelet aggregation measured by light transmission aggregometry following stimulation with arachidonic acid, ADP, and TRAP-6 after each treatment period. |
| Platelet surface activation markers | Baseline and Day 14 of each treatment period (up to 42 days) | Change from baseline in platelet surface expression of CD62P (P-selectin) and activated GPIIb/IIIa measured by flow cytometry following aspirin and clopidogrel treatment. |
| Biochemical verification of aspirin pharmacodynamic effect | Day 14 of the aspirin treatment period | Serum thromboxane B2 (TxB2) concentration measured to verify cyclooxygenase-1 inhibition during aspirin treatment. |
| Biochemical verification of clopidogrel pharmacodynamic effect | Day 14 of the clopidogrel treatment period | Vasodilator-stimulated phosphoprotein (VASP) platelet reactivity index (PRI) measured to verify P2Y12 receptor inhibition during clopidogrel treatment. |
| Association between plasma lipoprotein(a) concentration and platelet function | Baseline and Day 14 of each treatment period (up to 42 days) | Correlation between plasma lipoprotein(a) concentration and platelet function parameters measured by light transmission aggregometry, flow cytometry, and soluble biomarkers. |
| Baseline comparison of platelet reactivity between participants with high and low lipoprotein(a) | Baseline (Day 0) | Comparison of baseline platelet function parameters between participants with elevated lipoprotein(a) (\>125 nmol/L) and matched participants with low lipoprotein(a) (\<25 nmol/L). |
| Plasma proteomic profile associated with lipoprotein(a) and antiplatelet therapy (Exploratory) | Baseline and Day 14 of each treatment period (up to 42 days) | Exploratory analysis of plasma proteins measured using the Olink® proximity extension assay platform to identify proteins associated with elevated lipoprotein(a), platelet reactivity, and treatment with aspirin or clopidogrel. |
Countries
Switzerland
Contacts
CONTACTKapka Miteva, PhD
PRINCIPAL_INVESTIGATORFrançois Mach, Prof
HUG
Outcome results
None listed