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Study of the Long-term Effects of P2Y12 Inhibitor Monotherapy and Coagulation Markers After Percutaneous Coronary Angioplasty. (HI-TECH 2)

2026年5月6日 更新者：Marco Valgimigli、Cardiocentro Ticino

Hunting for the Long-Term EffeCts of P2Y12 Inhibitor monotHerapy and Coagulation Monitoring After PCI: an Open-label, Randomized Study.

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.

研究概览

地位

招聘中

条件

干预/治疗

详细说明

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.

研究类型

介入性

注册 (估计的)

355

阶段

  • 第三阶段

联系人和位置

本节提供了进行研究的人员的详细联系信息，以及有关进行该研究的地点的信息。

学习联系方式

  • 姓名：Marco Valgimigli, Cardiology Chief Prof. Dr. Med
  • 电话号码：+41 (0) 91 811 51 11
  • 邮箱：marco.valgimigli@eoc.ch

研究联系人备份

学习地点

  • 瑞士
    • Ch/ti
      • Lugano、Ch/ti、瑞士、6900
        • 招聘中
        • Istituto Cardiocentro Ticino
        • 接触：
          • Servizio di Ricerca Cardiovascolare Cardiocentro, +41 (0)91 811 53 04
          • 邮箱：src.ICCT@eoc.ch

参与标准

研究人员寻找符合特定描述的人，称为资格标准。这些标准的一些例子是一个人的一般健康状况或先前的治疗。

资格标准

适合学习的年龄

  • 成人
  • 年长者

接受健康志愿者

不

描述

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

学习计划

本节提供研究计划的详细信息，包括研究的设计方式和研究的衡量标准。

研究是如何设计的？

设计细节

  • 主要用途：治疗
  • 分配：随机化
  • 介入模型：并行分配
  • 屏蔽：无（打开标签）

武器和干预

参与者组/臂
干预/治疗
有源比较器：Clopidogrel Monotherapy (Standard Dose) (Phase 2)
Participants receive clopidogrel 75 mg once daily as standard-dose P2Y12 inhibitor monotherapy after completion of dual antiplatelet therapy following PCI.
药品：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.
其他名称：
  • 波立维
实验性的：Ticagrelor Monotherapy (Optimized Dose) (Phase 2)
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.
药品：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.
其他名称：
  • 布里利克
实验性的：Prasugrel Monotherapy (Optimized Dose) (Phase 2)
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.
药品：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.
其他名称：
  • 高效

研究衡量的是什么？

主要结果指标

结果测量
措施说明
大体时间
Identification of reduced doses of ticagrelor and prasugrel achieving target platelet reactivity by VerifyNow (Phase 1)
大体时间：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).
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)
大体时间：3 months after randomization
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

次要结果测量

结果测量
措施说明
大体时间
Identification of reduced doses of ticagrelor and prasugrel achieving target platelet reactivity by Multiplate (Phase 1)
大体时间：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).
Identification of the reduced maintenance doses of ticagrelor and prasugrel that achieve platelet reactivity within the predefined therapeutic window, defined as area under the curve (AUC) ≥18 and ≤46, as measured by the Multiplate analyzer. 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 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)
大体时间：3 months after randomization (Phase 2)
Proportion of patients with platelet reactivity within the predefined therapeutic window, defined as area under the curve (AUC) ≥18 and ≤46, as measured by the Multiplate analyzer. Platelet reactivity is assessed 1 to 2 hours after witnessed intake of the maintenance dose.
3 months after randomization (Phase 2)
Platelet reactivity within the therapeutic window after loading dose and at 6 months after randomization (Phase 2)
大体时间：At randomization and 6 months after randomization (Phase 2)
Proportion of patients achieving platelet reactivity within the predefined therapeutic window (PRU 85-208 by VerifyNow and/or AUC 18-46 by Multiplate) at baseline, at 3 to 6 hours after administration of the loading dose of the randomized P2Y12 inhibitor, and at 6 months follow-up, 1 to 2 hours after witnessed intake of the maintenance dose.
At randomization and 6 months after randomization (Phase 2)
Proportion of patients with high and low platelet reactivity (Phase 2)
大体时间：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)
Proportion of patients with high platelet reactivity (HPR: PRU ≥208 or AUC ≥46) and low platelet reactivity (LPR: PRU ≤85 or AUC ≤18), as assessed by the VerifyNow P2Y12 assay and Multiplate analyzer. Measurements will be performed 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.
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)
大体时间：Up to 6 months after randomization (Phase 2)
Composite of death, myocardial infarction, or stroke, and individual components.
Up to 6 months after randomization (Phase 2)
BARC bleeding events (Phase 2)
大体时间：Up to 6 months after randomization (Phase 2)
Bleeding events classified according to the Bleeding Academic Research Consortium (BARC) criteria. The BARC scale ranges from 0 to 5, where 0 indicates no bleeding and 5 indicates fatal bleeding; higher scores correspond to worse outcomes.
Up to 6 months after randomization (Phase 2)
Drug adherence (Phase 2)
大体时间：Up to 6 months after randomization (Phase 2)
Assessment of treatment adherence measured as the proportion of prescribed doses taken over the study period, expressed as a percentage (0% to 100%), where higher percentages indicate better adherence. Adherence will be evaluated using patient self-report (e.g., medication diary) and, where available, electronic adherence monitoring systems (e.g., automatic pill counting devices).
Up to 6 months after randomization (Phase 2)
Drug tolerability (Phase 2)
大体时间：Up to 6 months after randomization (Phase 2)
Assessment of drug tolerability based on the incidence, type, and severity of adverse events and treatment discontinuations, as documented in the annual safety report. Adverse events will be summarized descriptively; higher incidence and greater severity indicate worse tolerability.
Up to 6 months after randomization (Phase 2)
Correlation between genotype status and platelet reactivity measured by VerifyNow P2Y12 assay (Phase 2)
大体时间：Up to 6 months after randomization (Phase 2)
Assessment of the correlation between genotype status-including variants of CYP2C19 and ABCB1, determined by genotyping assay-and platelet reactivity measured by the VerifyNow P2Y12 assay, expressed in P2Y12 Reaction Units (PRU). Correlation will be quantified using an appropriate correlation coefficient (e.g., Pearson or Spearman), ranging from -1 to +1, where values closer to ±1 indicate stronger relationships.
Up to 6 months after randomization (Phase 2)
Change in cardiac troponin levels (Phase 2)
大体时间：From baseline to 6 months after randomization
Change from baseline in cardiac troponin concentration, measured in ng/L using a validated immunoassay. Higher values indicate greater cardiac injury.
From baseline to 6 months after randomization
Change in prothrombin fragment 1+2 levels (Phase 2)
大体时间：From baseline to 6 months after randomization
Change from baseline in prothrombin fragment 1+2 concentration, measured in pmol/L using a validated assay. Higher values indicate increased thrombin generation.
From baseline to 6 months after randomization
Change in thrombin-antithrombin (TAT) complex levels (Phase 2)
大体时间：From baseline to 6 months after randomization
Change from baseline in thrombin-antithrombin complex concentration, measured in µg/L. Higher values indicate increased coagulation activation.
From baseline to 6 months after randomization
Change in fibrinopeptide A levels (Phase 2)
大体时间：From baseline to 6 months after randomization
Change from baseline in fibrinopeptide A concentration, measured in ng/mL. Higher values indicate increased fibrin formation.
From baseline to 6 months after randomization
Change in fibrinogen levels (Phase 2)
大体时间：From baseline to 6 months after randomization
Change from baseline in fibrinogen concentration, measured in g/L. Higher values indicate increased coagulation potential.
From baseline to 6 months after randomization
Change in fibrin monomer levels (Phase 2)
大体时间：From baseline to 6 months after randomization
Change from baseline in fibrin monomer concentration, measured in µg/mL. Higher values indicate increased fibrin formation.
From baseline to 6 months after randomization
Change in D-dimer levels (Phase 2)
大体时间：From baseline to 6 months after randomization
Change from baseline in D-dimer concentration, measured in mg/L FEU. Higher values indicate increased fibrinolysis and clot turnover.
From baseline to 6 months after randomization
Change in von Willebrand factor activity (Phase 2)
大体时间：From baseline to 6 months after randomization
Change from baseline in von Willebrand factor activity, expressed as a percentage (%). Higher values indicate increased platelet adhesion activity.
From baseline to 6 months after randomization
Change in plasminogen activator inhibitor-1 (PAI-1) levels (Phase 2)
大体时间：From baseline to 6 months after randomization
Change from baseline in PAI-1 concentration, measured in ng/mL. Higher values indicate reduced fibrinolysis.
From baseline to 6 months after randomization
Change in thrombin-activatable fibrinolysis inhibitor (TAFI) levels (Phase 2)
大体时间：From baseline to 6 months after randomization
Change from baseline in TAFI concentration, measured in µg/mL. Higher values indicate reduced fibrinolysis.
From baseline to 6 months after randomization
Change in circulating extracellular vesicle levels (Phase 2)
大体时间：From baseline to 6 months after randomization
Change from baseline in circulating extracellular vesicle concentration, measured as particles/µL using a validated analytical method. Higher values may reflect increased cellular activation or injury.
From baseline to 6 months after randomization

合作者和调查者

在这里您可以找到参与这项研究的人员和组织。

赞助

Cardiocentro Ticino

调查人员

  • 首席研究员：Marco Valgimigli, Cardiology Chief Prof. Dr. Med、Cardiocentro Ticino

研究记录日期

这些日期跟踪向 ClinicalTrials.gov 提交研究记录和摘要结果的进度。研究记录和报告的结果由国家医学图书馆 (NLM) 审查，以确保它们在发布到公共网站之前符合特定的质量控制标准。

研究主要日期

学习开始 (估计的)

2026年4月20日

初级完成 (估计的)

2028年4月1日

研究完成 (估计的)

2028年4月1日

研究注册日期

首次提交

2026年4月14日

首先提交符合 QC 标准的

2026年5月6日

首次发布 (实际的)

2026年5月13日

研究记录更新

最后更新发布 (实际的)

2026年5月13日

上次提交的符合 QC 标准的更新

2026年5月6日

最后验证

2026年4月1日

更多信息

与本研究相关的术语

关键字

其他相关的 MeSH 术语

其他研究编号

  • 2026-00247

药物和器械信息、研究文件

研究美国 FDA 监管的药品

不

研究美国 FDA 监管的设备产品

不

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