Study of the Long-term Effects of P2Y12 Inhibitor Monotherapy and Coagulation Markers After Percutaneous Coronary Angioplasty.
For patients and families
In plain language
An automatic summary of structured registry data. It is an orientation aid, not a substitute for the official protocol or a physician assessment.
- What is being studied
- The protocol lists: Clopidogrel, Ticagrelor, Prasugrel.
- Who it may be relevant to
- Registry conditions: Coronary Artery Disease, Percutaneous Coronary Intervention, Acute Coronary Syndromes, Antiplatelet Therapy. Basic parameters: from 18 years · All.
- What needs checking
- Age, condition and sex are only basic indicators. Prior treatment, laboratory values and other mandatory requirements appear in the eligibility criteria below.
- Where it takes place
- Switzerland
- Next step
- Save the trial, show it to the treating physician, and confirm current recruitment with the study center. Costs, documents and travel →
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Official title
Hunting for the Long-Term EffeCts of P2Y12 Inhibitor monotHerapy and Coagulation Monitoring After PCI: an Open-label, Randomized Study.
Overview
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.
Detailed description
HI-TECH 2 is a prospective, investigator-initiated, single-center, open-label clinical trial designed to optimize P2Y12 inhibitor monotherapy following percutaneous coronary intervention (PCI), with a focus on achieving a predefined therapeutic window of platelet reactivity and characterizing coagulation system activation over time.
Despite widespread use of P2Y12 inhibitor monotherapy after completion of dual antiplatelet therapy (DAPT), substantial interindividual variability in pharmacodynamic response persists. Both high platelet reactivity (HPR) and low platelet reactivity (LPR) have been associated with adverse clinical outcomes, including thrombotic and bleeding events, respectively. A therapeutic window of platelet reactivity has been proposed to balance these competing risks. However, the optimal drug selection and dosing strategy to consistently achieve this window in contemporary PCI patients remain uncertain.
The study is structured in two sequential phases.
Phase 1 (dose-finding phase):
This phase aims to identify reduced-dose regimens of ticagrelor and prasugrel that achieve platelet reactivity within the predefined therapeutic range. Patients eligible for P2Y12 inhibitor monotherapy after PCI undergo serial platelet function testing using two validated assays (VerifyNow and Multiplate) at steady state. Ticagrelor and prasugrel are administered with stepwise dose reductions at predefined intervals, allowing within-subject pharmacodynamic assessment across multiple dosing regimens. The relationship between drug dose and platelet reactivity is characterized to determine the dose associated with the highest proportion of measurements within the target therapeutic window.
Phase 2 (randomized phase):
Following identification of the optimal dosing regimens in Phase 1, patients are randomized in a 1:1:1 ratio to receive clopidogrel at standard dose or ticagrelor or prasugrel at the optimized regimens. Randomization is stratified according to key clinical variables, including clinical presentation and diabetic status. Platelet function testing is performed under standardized conditions to assess pharmacodynamic response at steady state. This phase is designed to compare the proportion of patients achieving platelet reactivity within the therapeutic window across treatment groups.
In addition to platelet function assessment, a comprehensive panel of circulating biomarkers is evaluated in a predefined subset of patients to investigate the activation and persistence of coagulation pathways following PCI. These biomarkers include markers of thrombin generation, fibrinolysis, endothelial function, and platelet activation, providing mechanistic insight into the interplay between platelet inhibition and coagulation system activity in the chronic phase after PCI.
Pharmacogenetic analyses are also incorporated to explore the influence of CYP2C19 genotype and a composite ABCD-gene score on treatment response and the likelihood of achieving the therapeutic window. This component aims to assess the potential role of genotype-guided strategies in tailoring P2Y12 inhibitor therapy.
All analyses in the randomized phase are primarily conducted according to the intention-to-treat principle, with complementary per-protocol analyses to evaluate the robustness of findings. The study is powered to detect clinically relevant differences in pharmacodynamic response between treatment strategies, with adjustment for multiple comparisons.
Overall, HI-TECH 2 integrates dose optimization, randomized comparison, biomarker profiling, and pharmacogenetics to provide a comprehensive evaluation of long-term P2Y12 inhibitor monotherapy after PCI. The results are expected to inform individualized antiplatelet strategies aimed at improving the balance between thrombotic and bleeding risk in this population.
Interventions
- Drug Clopidogrel
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. - Drug Ticagrelor
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. - Drug Prasugrel
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.
Primary outcome measures
- Identification of reduced doses of ticagrelor and prasugrel achieving target platelet reactivity by VerifyNow (Phase 1) [Time frame: 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) [Time frame: 3 months after randomization]
Secondary outcome measures (12)
- Identification of reduced doses of ticagrelor and prasugrel achieving target platelet reactivity by Multiplate (Phase 1) [Time frame: 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) [Time frame: 3 months after randomization (Phase 2)]
- Platelet reactivity within the therapeutic window after loading dose and at 6 months after randomization (Phase 2) [Time frame: At randomization and 6 months after randomization (Phase 2)]
- Proportion of patients with high and low platelet reactivity (Phase 2) [Time frame: 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) [Time frame: Up to 6 months after randomization (Phase 2)]
- BARC bleeding events (Phase 2) [Time frame: Up to 6 months after randomization (Phase 2)]
- Drug adherence (Phase 2) [Time frame: Up to 6 months after randomization (Phase 2)]
- Drug tolerability (Phase 2) [Time frame: Up to 6 months after randomization (Phase 2)]
- Correlation between genotype status and platelet reactivity measured by VerifyNow P2Y12 assay (Phase 2) [Time frame: Up to 6 months after randomization (Phase 2)]
- Change in cardiac troponin levels (Phase 2) [Time frame: From baseline to 6 months after randomization]
- Change in prothrombin fragment 1+2 levels (Phase 2) [Time frame: From baseline to 6 months after randomization]
- Change in thrombin-antithrombin (TAT) complex levels (Phase 2) [Time frame: From baseline to 6 months after randomization]
Eligibility criteria
Inclusion criteria
- 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.
Exclusion criteria
- 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
Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.
Healthy volunteers: No
Study design
- Allocation
- Randomized
- Model
- Parallel assignment
- Masking
- Open label
- Primary purpose
- Treatment
Study locations
Switzerland · 1 center
- Istituto Cardiocentro Ticino — Lugano
Identifiers
NCT: NCT07582835 · 2026-00247