Study of the Long-term Effects of P2Y12 Inhibitor Monotherapy and Coagulation Markers After Percutaneous Coronary Angioplasty.

NCT07582835 | Recruiting Phase 3

• 1 other identifier: 2026-00247
• Study Type: interventional
• Target: 355
• Locations: 1 country
• Sites: 1

Brief Summary

Patients who undergo percutaneous coronary intervention (PCI) are commonly treated with antiplatelet therapy to prevent stent thrombosis and recurrence of events. After an initial period of dual antiplatelet therapy, long-term treatment with a single P2Y12 inhibitor (such as clopidogrel, ticagrelor, or prasugrel) is often prescribed. However, the optimal drug and dose for long-term monotherapy remain uncertain, as patients may experience either insufficient platelet inhibition (leading to ischemic events) or excessive inhibition (increasing bleeding risk). The HI-TECH 2 study aims to identify the most appropriate type and dose of P2Y12 inhibitor monotherapy to achieve a balanced level of platelet inhibition within a predefined therapeutic range. The study also seeks to better understand how blood coagulation activity evolves over time after PCI. This is a prospective, investigator-initiated, single-center, open-label study conducted in two phases. In Phase 1, patients receive stepwise reduced doses of ticagrelor or prasugrel to determine the optimal dose that most consistently achieves the desired level of platelet inhibition. In Phase 2, patients are randomly assigned to receive clopidogrel or the optimal doses of ticagrelor or prasugrel identified in Phase 1. The main question of the study is whether optimized ticagrelor or prasugrel regimens are more effective than standard-dose clopidogrel in achieving platelet inhibition within the target therapeutic window, as measured by validated platelet function tests. Additional objectives include evaluating the role of genetic factors in treatment response and assessing markers of coagulation activation over time. The results of this study may help personalize long-term antiplatelet therapy after PCI, improving the balance between reducing thrombotic risk and minimizing bleeding complications.

Conditions

Coronary Artery Disease; Percutaneous Coronary Intervention; Acute Coronary Syndromes; Antiplatelet Therapy; Single Antiplatelet Therapy; Coagulation Factors

Keywords

Coronary Artery Disease; Single Antiplatelet Therapy; Antiplatelet therapy; Ticagrelor; Prasugrel; Coagulation biomarkers; Clopidogrel; Multiplate; VerifyNow; CYP2C19; ABCB1 gene; Acute Coronary Syndromes; Dose optimization; platelet function tests (PFT); Percutaneous Coronary Intervention (PCI); High platelet reactivity (HPR); Low platelet reactivity (LPR); Bleeding Risk; Ischemic risk; prothrombin fragment F1+2; thrombin-antithrombin (TAT) complex; fibrinopeptide A; fibrinogen; D-dimer; von Willebrand factor activity (VWF); plasminogen activator inhibitor-1 (PAI-1); thrombin-activatable fibrinolysis inhibitor (TAFI); circulating extracellular vesicles

Outcome Measures

Primary Outcomes (2)

• Identification of reduced doses of ticagrelor and prasugrel achieving target platelet reactivity by VerifyNow (Phase 1)

  Identification of the reduced maintenance doses of ticagrelor and prasugrel that achieve platelet reactivity within the predefined therapeutic window, defined as platelet reactivity units (PRU) \>85 and \<208, as measured by the VerifyNow P2Y12 assay. Platelet reactivity will be assessed 1 to 2 hours after intake of each dose of the P2Y12 inhibitor.

  During the dose-finding phase (Phase 1): at baseline and at Visit 1 (at approximately 30 days), Visit 2 (at approximately 60 days), and Visit 3 (at approximately 90 days).

• Proportion of patients achieving platelet reactivity within the therapeutic window by VerifyNow at 3 months after randomization (Phase 2)

  Proportion of patients with platelet reactivity within the predefined therapeutic window, defined as platelet reactivity units (PRU) ≥85 and ≤208, as measured by the VerifyNow P2Y12 assay. Platelet reactivity is assessed 1 to 2 hours after witnessed intake of the maintenance dose. The primary analysis includes two comparisons: ticagrelor versus clopidogrel and prasugrel versus clopidogrel.

  3 months after randomization

Secondary Outcomes (20)

• Identification of reduced doses of ticagrelor and prasugrel achieving target platelet reactivity by Multiplate (Phase 1)

  During the dose-finding phase (Phase 1): at baseline and at Visit 1 (at approximately 30 days), Visit 2 (at approximately 30 days), and Visit 3 (at approximately 30 days).

• Proportion of patients achieving platelet reactivity within the therapeutic window by Multiplate at 3 months after randomization (Phase 2)

  3 months after randomization (Phase 2)

• Platelet reactivity within the therapeutic window after loading dose and at 6 months after randomization (Phase 2)

  At randomization and 6 months after randomization (Phase 2)

• Proportion of patients with high and low platelet reactivity (Phase 2)

  At baseline, 3 to 6 hours after the loading dose following randomization, and 1 to 2 hours after intake of the maintenance dose at approximately 3 months and 6 months. (Phase 2)

• Major adverse cardiovascular events (MACE) (Phase 2)

  Up to 6 months after randomization (Phase 2)

Study Arms (3)

Clopidogrel Monotherapy (Standard Dose) (Phase 2)

ACTIVE COMPARATOR

Participants receive clopidogrel 75 mg once daily as standard-dose P2Y12 inhibitor monotherapy after completion of dual antiplatelet therapy following PCI.

Drug: Clopidogrel

Ticagrelor Monotherapy (Optimized Dose) (Phase 2)

EXPERIMENTAL

Participants receive ticagrelor monotherapy at the optimized maintenance dose identified in Phase 1 of the study after discontinuation of dual antiplatelet therapy following PCI. Dose selection is based on prior dose-finding platelet function testing.

Drug: Ticagrelor

Prasugrel Monotherapy (Optimized Dose) (Phase 2)

EXPERIMENTAL

Participants receive prasugrel monotherapy at the optimized maintenance dose identified in Phase 1 of the study after discontinuation of dual antiplatelet therapy following PCI. Dose selection is based on prior dose-finding platelet function testing.

Drug: Prasugrel

Interventions

Clopidogrel DRUG

Clopidogrel 75 mg once daily administered as maintenance P2Y12 inhibitor monotherapy following completion of dual antiplatelet therapy after PCI. This regimen represents the standard comparator arm in the study.

Also known as: Plavix

Clopidogrel Monotherapy (Standard Dose) (Phase 2)

Ticagrelor DRUG

Ticagrelor monotherapy administered at the optimized maintenance dose identified in Phase 1 dose-finding stage. Dose selection is based on stepwise dose reduction with serial platelet function testing (VerifyNow P2Y12 and Multiplate) to achieve platelet reactivity within the predefined therapeutic window. Administered after completion of dual antiplatelet therapy following PCI.

Also known as: Brilique

Ticagrelor Monotherapy (Optimized Dose) (Phase 2)

Prasugrel DRUG

Prasugrel monotherapy administered at the optimized maintenance dose identified in Phase 1 dose-finding stage. Dose selection is based on stepwise dose reduction with serial platelet function testing (VerifyNow P2Y12 and Multiplate) to achieve platelet reactivity within the predefined therapeutic window. Administered after completion of dual antiplatelet therapy following PCI.

Also known as: Efient

Prasugrel Monotherapy (Optimized Dose) (Phase 2)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥18 years
• Prior (≥3 months) ACS and/or PCI
• Eligible for P2Y12 inhibitor monotherapy after an uneventful DAPT course
• Free from ischemic (i.e. any new episode of ACS, symptomatic restenosis, stent thrombosis, stroke, any revascularization requiring prolonged DAPT) and/or bleeding events (defined as BARC ≥ 2) for at least 3 months
• Written informed consent.

You may not qualify if:

• Unconscious patients
• Unable to provide written informed consent
• Under judicial protection, tutorship or curatorship
• Unable to understand and follow study-related instructions or unable to comply with study protocol
• Known hypersensitivity or allergy to clopidogrel, ticagrelor or prasugrel
• Severe hepatic impairment
• Haemoglobin level \<10 g/dL or platelet count \<100 000 cells/mL
• Pregnant or breastfeeding women
• Life expectancy less than 1 year
• Active participation in another interventional trial
• Need for concomitant oral anticoagulation
• History of intracranial haemorrhage (anytime), transient ischemic attack or stroke within 3 months
• PCI for in-stent restenosis or stent thrombosis at index PCI or within 6 months before randomization

Sponsors & Collaborators

• Cardiocentro Ticino: lead

Study Sites (1)

Istituto Cardiocentro Ticino

Lugano, Ch/ti, 6900, Switzerland

RECRUITING

MeSH Terms

Conditions

Coronary Artery Disease; Acute Coronary Syndrome

Interventions

Clopidogrel; Ticagrelor; Prasugrel Hydrochloride

Condition Hierarchy (Ancestors)

Coronary Disease; Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Vascular Diseases

Intervention Hierarchy (Ancestors)

Ticlopidine; Thienopyridines; Thiophenes; Sulfur Compounds; Organic Chemicals; Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Adenosine; Purine Nucleosides; Purines; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleosides; Piperazines

Study Officials

• Marco Valgimigli, Cardiology Chief Prof. Dr. Med

  Cardiocentro Ticino

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Marco Valgimigli, Cardiology Chief Prof. Dr. Med

CONTACT

+41 (0) 91 811 51 11; marco.valgimigli@eoc.ch

Enrico Frigoli, Dr. Med

CONTACT

+41 (0)91 811 53 04; enrico.frigoli@eoc.ch

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Cardiology Chief Prof. Dr. Med

Model Details: This is a two-phase interventional study. Phase 1 consists of a prospective dose-finding design in which patients receive stepwise reductions of ticagrelor or prasugrel monotherapy with serial platelet function testing to identify optimal dosing regimens achieving platelet reactivity within a predefined therapeutic window. Phase 2 is a randomized, open-label, parallel-group trial in which patients are assigned in a 1:1:1 ratio to clopidogrel, ticagrelor, or prasugrel at the optimized doses identified in Phase 1. Randomization is stratified by clinical presentation and diabetes status. Participants remain in their assigned treatment group throughout follow-up.

Study Record Dates

• First Submitted: April 14, 2026
• First Posted: May 13, 2026
• Study Start: April 20, 2026
• Primary Completion (Estimated): April 1, 2028
• Study Completion (Estimated): April 1, 2028
• Last Updated: May 13, 2026

Record last verified: 2026-04

Locations

CH (1)