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).
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
PREVENTION
Masking
SINGLE
Enrollment
60
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.
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.
Hopitaux Universitaires de Genève
Geneva, Switzerland
Change in collagen-induced platelet aggregation after aspirin versus clopidogrel treatment
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.
Time frame: Baseline and Day 14 of each treatment period (up to 42 days)
Change in soluble platelet activation biomarkers after aspirin versus clopidogrel treatment
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.
Time frame: Baseline and Day 14 of each treatment period (up to 42 days)
Agonist-specific platelet aggregation
Change from baseline in platelet aggregation measured by light transmission aggregometry following stimulation with arachidonic acid, ADP, and TRAP-6 after each treatment period.
Time frame: Baseline and Day 14 of each treatment period (up to 42 days)
Platelet surface activation markers
Change from baseline in platelet surface expression of CD62P (P-selectin) and activated GPIIb/IIIa measured by flow cytometry following aspirin and clopidogrel treatment.
Time frame: Baseline and Day 14 of each treatment period (up to 42 days)
Biochemical verification of aspirin pharmacodynamic effect
Serum thromboxane B2 (TxB2) concentration measured to verify cyclooxygenase-1 inhibition during aspirin treatment.
Time frame: Day 14 of the aspirin treatment period
Biochemical verification of clopidogrel pharmacodynamic effect
Vasodilator-stimulated phosphoprotein (VASP) platelet reactivity index (PRI) measured to verify P2Y12 receptor inhibition during clopidogrel treatment.
Time frame: Day 14 of the clopidogrel treatment period
Association between plasma lipoprotein(a) concentration and platelet function
Correlation between plasma lipoprotein(a) concentration and platelet function parameters measured by light transmission aggregometry, flow cytometry, and soluble biomarkers.
Time frame: 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)
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).
Time frame: Baseline (Day 0)
Plasma proteomic profile associated with lipoprotein(a) and antiplatelet therapy (Exploratory)
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.
Time frame: Baseline and Day 14 of each treatment period (up to 42 days)
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