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| Name | Class |
|---|---|
| Natasha Irrera | UNKNOWN |
| Gianluca Di Bella | UNKNOWN |
| Antonio Micari | UNKNOWN |
| Roberto Licordari |
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This is a single-center, prospective, observational controlled cohort study designed to describe the role of WNT/B-catenin signaling and adenosine system after an acute myocardial infarction, correlating it with clinical markers of fibrosis/remodeling (primary objective). The modulation of the aforementioned molecular patterns will also be evaluated in light of the type of P2Y12 inhibitor implemented (ticagrelor or prasugrel) to identify variations in response (secondary objective).
A total of 50 patients will be enrolled in the study, 40 with clinical presentation of acute myocardial infarction and eligible for treatment with either prasugrel or ticagrelor, and a control cohort of 10 patients with stable coronary artery disease, matched for age, sex and major risk factors, and with no history of prior myocardial infarction.
The study has been approved by the local ethics committee on 22/09/2021. Pre-enrollment screening will start from 01/11/2021. Blood samples will be obtained at 5 time-points: before and immediately after coronary revascularization (PCI) through the arterial introducer, and in the ward / clinic at a distance of 3, 5 days and 45±15 days from the procedure during normal routine examinations.
These will be used to study the expression of messenger RNA encoding for beta-catenin and to dose concentrations of beta-catenin, adenosine and cyclic adenosine monophosphate (cAMP) on serum. The extraction of RNA from blood samples will be carried out with a Real-time PCR method and the determination of molecules using ELISA colorimetric method, using specific kits.
Clinical-laboratory markers of left ventricular remodeling such as NT-proBNP, hsTnT, C-reactive protein, CK-MB, 12-lead ECG, transthoracic echocardiogram and cardiac magnetic resonance imaging, will be evaluated during hospitalization (at 3 and 5 days) and at the control visit (at 45 ± 15 days) as per standard clinical practice.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Acute Myocardial Infarction | 40 patients with clinical presentation of acute myocardial infarction undergoing primary percutaneous coronary intervention and eligible for dual antiplatelet therapy (DAPT) with either prasugrel or ticagrelor on top of aspirin. |
| |
| Chronic Coronary Syndrome | 10 patients with stable coronary artery disease with an indication, according to current guidelines, to percutaneous coronary intervention and subsequent DAPT with aspirin and clopidogrel. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| P2Y12 Potent Inhibitor + Aspirin for STEMI patients | Drug | Patients will undergo primary percutaneous coronary intervention and DAPT with potent P2Y12 inhibitor (ticagrelor or prasugrel + aspirin) |
| Measure | Description | Time Frame |
|---|---|---|
| Correlation between WNT/B-catenin levels and NTproBNP in patients presenting with acute myocardial infarction | NTproBNP as per center standard dosing | Measured at 5 days after PCI |
| Correlation between WNT/B-catenin levels and and left ventricular ejection fraction in patients presenting with acute myocardial infarction | Left ventricular ejection fraction will be measured with transthoracic Echocardiography at the specified timepoint | Measured at 5 days after PCI |
| Correlation between WNT/B-catenin levels and and extent of myocardial necrosis in patients presenting with acute myocardial infarction | Extent of myocardial necrosis will be measured with Carciac Magnetic Resonance Imaging at the specified timepoint | Measured at 5 days after PCI |
| Correlation between in hospital WNT/B-catenin levels and NTproBNP at follow-up in patients presenting with acute myocardial infarction | NTproBNP as per center standard dosing | Measured at 45 day after PCI |
| Correlation between in-hospital WNT/B-catenin levels and left ventricular ejection fraction at follow-up in patients presenting with acute myocardial infarction | Left ventricular ejection fraction will be measured with transthoracic Echocardiography at the specified timepoint | Measured at 45 day after PCI |
| Correlation between in-hospital WNT/B-catenin levels and extent of myocardial fibrosis at follow-up in patients presenting with acute myocardial infarction | Extent of myocardial fibrosis will be measured with Carciac Magnetic Resonance Imaging at the specified timepoint |
| Measure | Description | Time Frame |
|---|---|---|
| Differences in WNT/B-catenin levels according to clinical presentation | Differences in results of activation of these molecular pathways in patients presenting with acute myocardial infarction and those selected in the control group by age, sex and risk factor matching | At baseline, 3, 5 and 45 day after PCI |
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Inclusion Criteria:
Patients with ST segment elevation acute myocardial infarction undergoing coronary angiography and interventional treatment.*
* Patients with chronic coronary syndrome matched by age, sex and risk factors will also be screened and included as per study design.
Patients with an indication to potent P2Y12 inhibitor therapy (i.e. ticagrelor or prasugrel) for acute myocardial infarction.
Population equally amenable to ticagrelor or prasugrel therapy according to the italian drug instruction of use (IFU)
Exclusion Criteria:
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The study population will consist of patients planned to undergo percutaneous coronary revascularization. A total of 50 patients will be enrolled in the study, 40 with clinical presentation of acute myocardial infarction with an indication for primary percutaneous coronary intervention and eligible for treatment with either prasugrel or ticagrelor, and a control cohort of 10 patients with stable coronary artery disease and no history of prior myocardial infarction who are not indicated for treatment with potent P2Y12 inhibitors.
To ensure comparability the study and control groups, the control cohort will be matched to exclude a potential confounder effect of age, sex and other established risk factors.
| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Francesco Costa | Contact | +390902212341 | dottfrancescocosta@gmail.com |
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| AOU Policlinico G. Martino | Recruiting | Messina | 98125 | Italy |
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| ID | Term |
|---|---|
| D009203 | Myocardial Infarction |
| D020257 | Ventricular Remodeling |
| ID | Term |
|---|---|
| D017202 | Myocardial Ischemia |
| D006331 | Heart Diseases |
| D002318 | Cardiovascular Diseases |
| D014652 | Vascular Diseases |
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| ID | Term |
|---|---|
| D001241 | Aspirin |
| C028145 | 2'-deoxythymidylyl-(3'-5')-2'-deoxyadenosine |
| D000077144 | Clopidogrel |
| ID | Term |
|---|---|
| D012459 | Salicylates |
| D062385 | Hydroxybenzoates |
| D010636 | Phenols |
| D001555 | Benzene Derivatives |
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| UNKNOWN |
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Blood samples will be used to study:
|
| Clopidogrel + Aspirin for CCS patients | Drug | Patients will undergo elective percutaneous coronary intervention and DAPT with non-potent P2Y12 inhibitor (clopidogrel + aspirin) |
|
|
| Measured at 45 day after PCI |
| Differences in WNT/B-catenin levels in patients treated with ticagrelor or prasugrel |
Differences in results of activation of these molecular pathways in patients treated with ticagrelor or prasugrel presenting with acute myocardial infarction |
| At baseline, 3, 5 and 45 day after PCI |
| Differences in WNT/B-catenin levels in patients treated with or without Sodium-glucose Cotransporter-2 (SGLT-2) inhibitors | Differences in results of activation of these molecular pathways in patients treated or not treated with Sodium-glucose Cotransporter-2 (SGLT-2) inhibitors after acute myocardial infarction | At baseline, 3, 5 and 45 day after PCI |
| D007238 |
| Infarction |
| D007511 | Ischemia |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D009336 | Necrosis |
| D020763 | Pathological Conditions, Anatomical |
| D006841 |
| Hydrocarbons, Aromatic |
| D006844 | Hydrocarbons, Cyclic |
| D006838 | Hydrocarbons |
| D009930 | Organic Chemicals |
| D013988 | Ticlopidine |
| D058924 | Thienopyridines |
| D013876 | Thiophenes |
| D013457 | Sulfur Compounds |
| D011725 | Pyridines |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |