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

January 21, 2023 updated by: Francesco Costa, University of Messina

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

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).

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed 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.

Study Type

Observational

Enrollment (Anticipated)

50

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Child
  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Sampling Method

Non-Probability Sample

Study Population

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.

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Observational Models: Cohort
  • Time Perspectives: Prospective

Cohorts and Interventions

Group / Cohort
Intervention / Treatment
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.
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
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.
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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Correlation between WNT/B-catenin levels and NTproBNP in patients presenting with acute myocardial infarction
Time Frame: Measured at 5 days after PCI
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
Time Frame: Measured at 5 days after PCI
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
Time Frame: Measured at 5 days after PCI
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
Time Frame: Measured at 45 day after PCI
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
Time Frame: Measured at 45 day after PCI
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
Time Frame: Measured at 45 day after PCI
Extent of myocardial fibrosis will be measured with Carciac Magnetic Resonance Imaging at the specified timepoint
Measured at 45 day after PCI

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Differences in WNT/B-catenin levels according to clinical presentation
Time Frame: 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
At baseline, 3, 5 and 45 day after PCI
Differences in WNT/B-catenin levels in patients treated with ticagrelor or prasugrel
Time Frame: 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
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
Time Frame: 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
At baseline, 3, 5 and 45 day after PCI

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Messina

Collaborators

Natasha Irrera
Gianluca Di Bella
Antonio Micari
Roberto Licordari

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

December 1, 2021

Primary Completion (Anticipated)

November 1, 2023

Study Completion (Anticipated)

December 31, 2023

Study Registration Dates

First Submitted

September 28, 2021

First Submitted That Met QC Criteria

November 15, 2021

First Posted (Actual)

November 17, 2021

Study Record Updates

Last Update Posted (Actual)

January 25, 2023

Last Update Submitted That Met QC Criteria

January 21, 2023

Last Verified

January 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • Cardio1

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

Undecided

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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