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

NCT07720934 | Not Yet Recruiting

• 1 other identifier: 2026-01415
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

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).

Conditions

Cardiovascular Prevention

Keywords

Lipoprotein(a)

Outcome Measures

Primary Outcomes (2)

• 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.

  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.

  Baseline and Day 14 of each treatment period (up to 42 days)

Secondary Outcomes (7)

• 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)

Other Outcomes (1)

• Identification of candidate biomarkers associated with lipoprotein(a)-related platelet hyperreactivity

  Baseline and Day 14 of each treatment period (up to 42 days)

Study Arms (2)

Aspirin → Clopidogrel Sequence

EXPERIMENTAL

Participants receive aspirin 100 mg once daily for 14 days, followed by a 14-day washout period, then clopidogrel 75 mg once daily for 14 days. Platelet function is assessed at baseline and after each treatment period.

Drug: Aspirin; Drug: Clopidogrel

Clopidogrel → Aspirin Sequence

EXPERIMENTAL

Participants receive clopidogrel 75 mg once daily for 14 days, followed by a 14-day washout period, then aspirin 100 mg once daily for 14 days. Platelet function is assessed at baseline and after each treatment period.

Drug: Aspirin; Drug: Clopidogrel

Interventions

Aspirin DRUG

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.

Aspirin → Clopidogrel Sequence; Clopidogrel → Aspirin Sequence

Clopidogrel DRUG

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.

Aspirin → Clopidogrel Sequence; Clopidogrel → Aspirin Sequence

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• 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).

You may not qualify if:

• 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.
• Any condition that, in the opinion of the investigator, would interfere with study participation, compliance, or interpretation of results.

Sponsors & Collaborators

• François MACH: lead
• University Hospital, Geneva: collaborator

Study Sites (1)

Hopitaux Universitaires de Genève

Geneva, 1205, Switzerland

Location

MeSH Terms

Interventions

Aspirin; Clopidogrel

Intervention Hierarchy (Ancestors)

Salicylates; Hydroxybenzoates; Phenols; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Ticlopidine; Thienopyridines; Thiophenes; Sulfur Compounds; Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Study Officials

• François Mach, Prof

  HUG

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Kapka Miteva, PhD

CONTACT

+41 22 379 4648; Kapka.Miteva@unige.ch

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor, MD

Study Record Dates

• First Submitted: July 17, 2026
• First Posted: July 22, 2026
• Study Start (Estimated): November 1, 2026
• Primary Completion (Estimated): March 1, 2027
• Study Completion (Estimated): November 1, 2027
• Last Updated: July 22, 2026

Record last verified: 2026-07

Data Sharing

• IPD Sharing: Will not share

Locations

CH (1)