Coronary Artery DiseasePhase 3HI-TECH 2NCT07582835
Study of the Long-term Effects of P2Y12 Inhibitor Monotherapy and Coagulation Markers After Percutaneous Coronary Angioplasty.
A Phase 3 study testing Clopidogrel, Ticagrelor and Prasugrel in people with Coronary Artery Disease and Percutaneous Coronary Intervention, run by Cardiocentro Ticino at 1 site in Switzerland.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Coronary Artery Disease, Percutaneous Coronary Intervention, Acute Coronary Syndromes
- What is being tested?
- Clopidogrel, Ticagrelor and Prasugrel
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 355 participants
- Where
- 1 siteSwitzerland
- Study dates
- 20 Apr 2026to Apr 2028
- Phase
- Phase 3
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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
Show all 13Show fewer
- 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
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Switzerland1 site, 1 recruiting
- Recruiting
Istituto Cardiocentro Ticino
Lugano, Ch/ti, 6900
Servizio di Ricerca Cardiovascolare Cardiocentro, +41 (0)91 811 53 04, src.ICCT@eoc.ch
About this study
Official title: 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.
Read more
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.
Read the 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.
- Conditions
- Coronary Artery Disease, Percutaneous Coronary Intervention, Acute Coronary Syndromes, Antiplatelet Therapy, Single Antiplatelet Therapy, Coagulation Factors
- Being tested
- Clopidogrel, Ticagrelor, Prasugrel
- 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
- Medical subject headings
- Coronary Artery Disease, Acute Coronary Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ClopidogrelDrug
Also called Plavix
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.
TicagrelorDrug
Also called Brilique
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.
PrasugrelDrug
Also called Efient
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.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: 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. Receives: Drug: Prasugrel |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: 3 months after randomization
Secondary outcomes (20)
Identification of reduced doses of ticagrelor and prasugrel achieving target platelet reactivity by Multiplate (Phase 1)
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.
Measured: 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)
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.
Measured: 3 months after randomization (Phase 2)
Platelet reactivity within the therapeutic window after loading dose and at 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.
Measured: At randomization and 6 months after randomization (Phase 2)
Proportion of patients with high and low platelet reactivity (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.
Measured: 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)
Composite of death, myocardial infarction, or stroke, and individual components.
Measured: Up to 6 months after randomization (Phase 2)
BARC bleeding events (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.
Measured: Up to 6 months after randomization (Phase 2)
Drug adherence (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).
Measured: Up to 6 months after randomization (Phase 2)
Drug tolerability (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.
Measured: Up to 6 months after randomization (Phase 2)
Correlation between genotype status and platelet reactivity measured by VerifyNow P2Y12 assay (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.
Measured: Up to 6 months after randomization (Phase 2)
Change in cardiac troponin levels (Phase 2)
Change from baseline in cardiac troponin concentration, measured in ng/L using a validated immunoassay. Higher values indicate greater cardiac injury.
Measured: From baseline to 6 months after randomization
Change in prothrombin fragment 1+2 levels (Phase 2)
Change from baseline in prothrombin fragment 1+2 concentration, measured in pmol/L using a validated assay. Higher values indicate increased thrombin generation.
Measured: From baseline to 6 months after randomization
Change in thrombin-antithrombin (TAT) complex levels (Phase 2)
Change from baseline in thrombin-antithrombin complex concentration, measured in µg/L. Higher values indicate increased coagulation activation.
Measured: From baseline to 6 months after randomization
Change in fibrinopeptide A levels (Phase 2)
Change from baseline in fibrinopeptide A concentration, measured in ng/mL. Higher values indicate increased fibrin formation.
Measured: From baseline to 6 months after randomization
Change in fibrinogen levels (Phase 2)
Change from baseline in fibrinogen concentration, measured in g/L. Higher values indicate increased coagulation potential.
Measured: From baseline to 6 months after randomization
Change in fibrin monomer levels (Phase 2)
Change from baseline in fibrin monomer concentration, measured in µg/mL. Higher values indicate increased fibrin formation.
Measured: From baseline to 6 months after randomization
Change in D-dimer levels (Phase 2)
Change from baseline in D-dimer concentration, measured in mg/L FEU. Higher values indicate increased fibrinolysis and clot turnover.
Measured: From baseline to 6 months after randomization
Change in von Willebrand factor activity (Phase 2)
Change from baseline in von Willebrand factor activity, expressed as a percentage (%). Higher values indicate increased platelet adhesion activity.
Measured: From baseline to 6 months after randomization
Change in plasminogen activator inhibitor-1 (PAI-1) levels (Phase 2)
Change from baseline in PAI-1 concentration, measured in ng/mL. Higher values indicate reduced fibrinolysis.
Measured: From baseline to 6 months after randomization
Change in thrombin-activatable fibrinolysis inhibitor (TAFI) levels (Phase 2)
Change from baseline in TAFI concentration, measured in µg/mL. Higher values indicate reduced fibrinolysis.
Measured: From baseline to 6 months after randomization
Change in circulating extracellular vesicle levels (Phase 2)
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.
Measured: From baseline to 6 months after randomization
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 May 2026
- Study start20 Apr 2026 (estimated)
- Primary completionApr 2028 (estimated)
- Study completionApr 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Coronary Artery DiseaseStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- 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.
- Masking
- None (open label)
- Enrolment
- 355 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Cardiocentro Ticino
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Marco Valgimigli, Cardiocentro Ticino
- Investigators
- Marco Valgimigli, Cardiology Chief Prof. Dr. Med, Principal investigator, Cardiocentro Ticino
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07582835
- Sponsor's protocol ID
- 2026-00247
- Acronym
- HI-TECH 2
- Status last verified
- Apr 2026
- First submitted
- 14 Apr 2026
- Last updated
- 13 May 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 13 May 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Hunting for the Long-Term EffeCts of P2Y12 Inhibitor monotHerapy and Coagulation Monitoring After PCI: an Open-label, Randomized Study.
- ClinicalTrials.gov ID
- NCT07582835
- Acronym / sponsor ID
- HI-TECH 2 / 2026-00247
- 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
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 355 participants (estimated)
- Lead sponsor
- Cardiocentro TicinoUniversity, hospital or other
- Study start
- 20 Apr 2026 (estimated)
- Primary completion
- Apr 2028 (estimated)
- Study completion
- Apr 2028 (estimated)
- First posted
- 13 May 2026 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
- Model description
- 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.
| Arm | Type | Receives |
|---|---|---|
| Clopidogrel Monotherapy (Standard Dose) (Phase 2) | Active comparator | Drug: ClopidogrelParticipants receive clopidogrel 75 mg once daily as standard-dose P2Y12 inhibitor monotherapy after completion of dual antiplatelet therapy following PCI. |
| Ticagrelor Monotherapy (Optimized Dose) (Phase 2) | Experimental | Drug: TicagrelorParticipants 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. |
| Prasugrel Monotherapy (Optimized Dose) (Phase 2) | Experimental | Drug: PrasugrelParticipants 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 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.
Key exclusion criteria (13 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| ClopidogrelAlso: PlavixClopidogrel 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 | Clopidogrel Monotherapy (Standard Dose) (Phase 2) |
| TicagrelorAlso: BriliqueTicagrelor 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 | Ticagrelor Monotherapy (Optimized Dose) (Phase 2) |
| PrasugrelAlso: EfientPrasugrel 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 Monotherapy (Optimized Dose) (Phase 2) |
Primary outcome
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).
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.
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
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.
20 secondary outcomes
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
Change in fibrinopeptide A levels (Phase 2)
Time frame: From baseline to 6 months after randomization
Change in fibrinogen levels (Phase 2)
Time frame: From baseline to 6 months after randomization
Change in fibrin monomer levels (Phase 2)
Time frame: From baseline to 6 months after randomization
Change in D-dimer levels (Phase 2)
Time frame: From baseline to 6 months after randomization
Change in von Willebrand factor activity (Phase 2)
Time frame: From baseline to 6 months after randomization
Change in plasminogen activator inhibitor-1 (PAI-1) levels (Phase 2)
Time frame: From baseline to 6 months after randomization
Change in thrombin-activatable fibrinolysis inhibitor (TAFI) levels (Phase 2)
Time frame: From baseline to 6 months after randomization
Change in circulating extracellular vesicle levels (Phase 2)
Time frame: From baseline to 6 months after randomization
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 May 2026.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Marco Valgimigli, Cardiology Chief Prof. Dr. Med principal investigator
Cardiocentro Ticino
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Clopidogrel, Ticagrelor and Prasugrel in people with Coronary Artery Disease and Percutaneous Coronary Intervention, run by Cardiocentro Ticino at 1 site in Switzerland.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 13 May 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Switzerland. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Marco Valgimigli, Cardiology Chief Prof. Dr. Med (+41 (0) 91 811 51 11, marco.valgimigli@eoc.ch), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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).). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 May 2026.