Modulation of the WNT/Beta-Catenin Pathway in Patients With Acute Myocardial Infarction
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 50
- 试验地点
- 1
- 主要终点
- Correlation between WNT/B-catenin levels and and left ventricular ejection fraction in patients presenting with acute myocardial infarction
研究概览
简要总结
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).
详细描述
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.
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Prospective
入排标准
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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)
排除标准
- •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
研究组 & 干预措施
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.
干预措施: P2Y12 Potent Inhibitor + Aspirin for STEMI patients (Drug)
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.
干预措施: Clopidogrel + Aspirin for CCS patients (Drug)
结局指标
主要结局
Correlation between WNT/B-catenin levels and and left ventricular ejection fraction in patients presenting with acute myocardial infarction
时间窗: 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 NTproBNP in patients presenting with acute myocardial infarction
时间窗: Measured at 5 days after PCI
NTproBNP as per center standard dosing
Correlation between WNT/B-catenin levels and and extent of myocardial necrosis in patients presenting with acute myocardial infarction
时间窗: 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
时间窗: 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
时间窗: 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
时间窗: Measured at 45 day after PCI
Extent of myocardial fibrosis will be measured with Carciac Magnetic Resonance Imaging at the specified timepoint
次要结局
- Differences in WNT/B-catenin levels according to clinical presentation(At baseline, 3, 5 and 45 day after PCI)
- Differences in WNT/B-catenin levels in patients treated with ticagrelor or prasugrel(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(At baseline, 3, 5 and 45 day after PCI)
研究者
Francesco Costa
Doctor
University of Messina