Clinical trial NCT05122741: Modulation of Fibrosis-inducing Pathways in Acute Myocardial Infarction
Official title: Modulation of the WNT/Beta-Catenin Pathway in Patients With Acute Myocardial Infarction
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Myocardial Infarction
Myocardial Fibrosis
Myocardial Remodeling, Ventricular
Keywords: Myocardial Infarction
Beta-Catenin
WNT Signaling pathway
Adenosine systems
Dual Antiplatelet Therapy
Ticagrelor
Prasugrel
Myocardial Fibrosis
Clopidogrel
Lead sponsor: University of Messina
Sponsor class: OTHER
Collaborators: name: Natasha Irrera
name: Gianluca Di Bella
name: Antonio Micari
name: Roberto Licordari
First posted: 2021-11-17
Enrollment: 50
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
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.

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).

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.

Eligibility criteria: 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

Primary outcomes:
measure: Correlation between WNT/B-catenin levels and NTproBNP in patients presenting with acute myocardial infarction
timeFrame: Measured at 5 days after PCI
measure: Correlation between WNT/B-catenin levels and and left ventricular ejection fraction in patients presenting with acute myocardial infarction
timeFrame: Measured at 5 days after PCI
measure: Correlation between WNT/B-catenin levels and and extent of myocardial necrosis in patients presenting with acute myocardial infarction
timeFrame: Measured at 5 days after PCI
measure: Correlation between in hospital WNT/B-catenin levels and NTproBNP at follow-up in patients presenting with acute myocardial infarction
timeFrame: Measured at 45 day after PCI
measure: Correlation between in-hospital WNT/B-catenin levels and left ventricular ejection fraction at follow-up in patients presenting with acute myocardial infarction
timeFrame: Measured at 45 day after PCI
measure: Correlation between in-hospital WNT/B-catenin levels and extent of myocardial fibrosis at follow-up in patients presenting with acute myocardial infarction
timeFrame: Measured at 45 day after PCI
Secondary outcomes:
measure: Differences in WNT/B-catenin levels according to clinical presentation
timeFrame: At baseline, 3, 5 and 45 day after PCI
measure: Differences in WNT/B-catenin levels in patients treated with ticagrelor or prasugrel
timeFrame: At baseline, 3, 5 and 45 day after PCI
measure: Differences in WNT/B-catenin levels in patients treated with or without Sodium-glucose Cotransporter-2 (SGLT-2) inhibitors
timeFrame: At baseline, 3, 5 and 45 day after PCI
Other outcomes:
Locations:
city: Messina
country: Italy
facility: AOU Policlinico G. Martino
Study officials:
References: