Modulation of Fibrosis-inducing Pathways in Acute Myocardial Infarction

Myocardial Infarction Clinical Trial

— BETA-MI  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05122741
• Other study ID #: Cardio1
• Status: Recruiting
• Start date: December 1, 2021
• Est. completion date: December 31, 2023

Study information

• Verified date: January 2023
• Source: University of Messina
• Contact: Francesco Costa
• Phone: +390902212341
• Email: dottfrancescocosta[@]gmail.com
• Is FDA regulated: No
• Study type: Observational [Patient Registry]

Clinical Trial 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).

Description:

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 50
• Est. completion date: December 31, 2023
• Est. primary completion date: November 1, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A and older

Eligibility

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:

• 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

Related Conditions & MeSH terms

• Fibrosis
• Infarction
• Myocardial Fibrosis
• Myocardial Infarction
• Myocardial Remodeling, Ventricular
• Ventricular Remodeling

Intervention

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)
• Clopidogrel + Aspirin for CCS patients
Patients will undergo elective percutaneous coronary intervention and DAPT with non-potent P2Y12 inhibitor (clopidogrel + aspirin)

Locations

Country	Name	City	State
Italy	AOU Policlinico G. Martino	Messina

Sponsors (5)

Lead Sponsor	Collaborator
University of Messina	Antonio Micari, Gianluca Di Bella, Natasha Irrera, Roberto Licordari

Country where clinical trial is conducted

Italy, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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	Measured at 45 day after PCI
Secondary	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
Secondary	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
Secondary	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