BETA-MI: Modulation of Fibrosis-inducing Pathways in Acute Myocardial Infarction

Sponsor

University of Messina (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT05122741

Collaborator

Natasha Irrera (Other), Gianluca Di Bella (Other), Antonio Micari (Other), Roberto Licordari (Other), Francesco Squadrito (Other)

100

Enrollment

Location

Anticipated Duration (Months)

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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).

Condition or Disease	Intervention/Treatment	Phase
Myocardial Infarction Myocardial Fibrosis Myocardial Remodeling, Ventricular	Drug: P2Y12 Potent Inhibitor + Aspirin for STEMI patients Drug: Clopidogrel + Aspirin for CCS patients

Detailed Description

A total of 100 patients will be enrolled in the study, 80 with clinical presentation of acute myocardial infarction and eligible for treatment with either prasugrel or ticagrelor, and a control cohort of 20 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.

Study Design

Study Type:

Observational [Patient Registry]

Anticipated Enrollment :

100 participants

Observational Model:

Cohort

Time Perspective:

Prospective

Official Title:

Modulation of the WNT/Beta-Catenin Pathway in Patients With Acute Myocardial Infarction

Anticipated Study Start Date :

Dec 1, 2021

Anticipated Primary Completion Date :

Nov 1, 2023

Anticipated Study Completion Date :

Dec 31, 2023

Arms and Interventions

Arm	Intervention/Treatment
Acute Myocardial Infarction 80 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.	Drug: P2Y12 Potent Inhibitor + Aspirin for STEMI patients Patients will undergo primary percutaneous coronary intervention and DAPT with potent P2Y12 inhibitor (ticagrelor or prasugrel + aspirin) Other Names: DAPT with Potent P2Y12i
Chronic Coronary Syndrome 20 patients with stable coronary artery disease with an indication, according to current guidelines, to percutaneous coronary intervention and subsequent DAPT with aspirin and clopidogrel.	Drug: Clopidogrel + Aspirin for CCS patients Patients will undergo elective percutaneous coronary intervention and DAPT with non-potent P2Y12 inhibitor (clopidogrel + aspirin) Other Names: DAPT with Clopidogrel

Arm

Intervention/Treatment

Acute Myocardial Infarction

80 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.

Drug: P2Y12 Potent Inhibitor + Aspirin for STEMI patients

Patients will undergo primary percutaneous coronary intervention and DAPT with potent P2Y12 inhibitor (ticagrelor or prasugrel + aspirin)

Other Names:

DAPT with Potent P2Y12i

Chronic Coronary Syndrome

20 patients with stable coronary artery disease with an indication, according to current guidelines, to percutaneous coronary intervention and subsequent DAPT with aspirin and clopidogrel.

Drug: Clopidogrel + Aspirin for CCS patients

Patients will undergo elective percutaneous coronary intervention and DAPT with non-potent P2Y12 inhibitor (clopidogrel + aspirin)

Other Names:

DAPT with Clopidogrel

Outcome Measures

Primary Outcome Measures

Correlation between WNT/B-catenin levels and NTproBNP in patients presenting with acute myocardial infarction [Measured at 5 days after PCI]
NTproBNP as per center standard dosing
Correlation between WNT/B-catenin levels and and left ventricular ejection fraction in patients presenting with acute myocardial infarction [Measured at 5 days after PCI]
Left ventricular ejection fraction will be measured with transthoracic Echocardiography at the specified timepoint
Correlation between WNT/B-catenin levels and and extent of myocardial necrosis in patients presenting with acute myocardial infarction [Measured at 5 days after PCI]
Extent of myocardial necrosis will be measured with Carciac Magnetic Resonance Imaging at the specified timepoint
Correlation between in hospital WNT/B-catenin levels and NTproBNP at follow-up in patients presenting with acute myocardial infarction [Measured at 45 day after PCI]
NTproBNP as per center standard dosing
Correlation between in-hospital WNT/B-catenin levels and left ventricular ejection fraction at follow-up in patients presenting with acute myocardial infarction [Measured at 45 day after PCI]
Left ventricular ejection fraction will be measured with transthoracic Echocardiography at the specified timepoint
Correlation between in-hospital WNT/B-catenin levels and extent of myocardial fibrosis at follow-up in patients presenting with acute myocardial infarction [Measured at 45 day after PCI]
Extent of myocardial fibrosis will be measured with Carciac Magnetic Resonance Imaging at the specified timepoint

Secondary Outcome Measures

Differences in WNT/B-catenin levels according to clinical presentation [At baseline, 3, 5 and 45 day after PCI]
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
Differences in WNT/B-catenin levels in patients treated with ticagrelor or prasugrel [At baseline, 3, 5 and 45 day after PCI]
Differences in results of activation of these molecular pathways in patients treated with ticagrelor or prasugrel presenting with acute myocardial infarction
Differences in WNT/B-catenin levels in patients treated with or without Sodium-glucose Cotransporter-2 (SGLT-2) inhibitors [At baseline, 3, 5 and 45 day after PCI]
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

Eligibility Criteria

Criteria

Ages Eligible for Study:

N/A and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Patients with anterior 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:

Patients with a poor prognosis (less than 12 months)
Patients admitted with cardiogenic shock or advanced cardiac failure (NYHA 4)
Patients pre-treated before coronary angiography or in chronic therapy with a P2Y12 inhibitor
Patients undergoing a medical only approach without percutaneous myocardial revascularization
Patients undergoing surgical coronary revascularization
Patients with prior history of myocardial infarction or prior coronary revascularization.
Patients with contraindications or intolerance to antiplatelet therapy (ticagrelor, prasugrel, clopidogrel or cardioaspirin)
Patients scheduled for a treatment with with cangrelor or GPIIb/IIIa inhibitors
Patients with active bleeding at the time of inclusion
Hemorrhagic diathesis
Confirmed history of renal failure with glomerular filtration rate of <30ml/min
Severe hepatopathy
Patients treated or scheduled for treatment with oral anticoagulant therapy
Active cancer or diagnosis any proliferative disease within 5 years.
Prior TIA or stroke (ischemic or hemorrhagic)
Age >75 years
Weight <60kg