Effect of Nicorandil for the Patients of Acute ST Segment Elevation Myocardial Infarction

Study Overview
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Brief Summary
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To evaluate whether nicorandil as an adjunctive therapy for acute myocardial infarction (AMI) reduces reperfusion injury.

Detailed Description
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Reperfusion injury might occur in patients with acute ST segment elevation myocardial infarction undergoing the primary percutaneous coronary intervention(P-PCI),characterized by myocardial stunning, reperfusion-induced arrhythmia, microvascular dysfunction and myocardial cellular apoptosis, etc. Nicorandil is an antianginal agent with a dual mechanism of action: nitrate and K+ATP channel opener. The nitrate action causes vasodilation of systemic veins and epicardial coronary arteries, while the adenosine triphosphate (ATP)-sensitive potassium channel opener action causes vasodilation of peripheral and coronary resistance arterioles. Nicorandil not only decreases preload and afterload but also increases coronary blood flow. The study will compare the effectiveness between nicorandil and placebo of preventing the reperfusion injury and left ventricle remodeling in patients with acute ST segment elevation myocardial infarction undergoing the P-PCI.It is intended that before reperfusion injury ,nicorandil which was early used by intracoronary injection could prevent and release the microcirculatory spasm, release the coronary microvascular endothelial swelling,decrease embolism of atherosclerotic debris and thrombus formation.So,it could decrease the phenomenon of no-reflow/slow reflow,reperfusion-induced arrhythmia and worsening of chest pain.

Official Title
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Effect of Early Administration of Intracoronary Nicorandil Via Thrombus Aspiration Catheter Device During Primary Percutaneous Coronary Intervention for the Patients of Acute ST Segment Elevation Myocardial Infarction

Conditions
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Coronary Heart Disease

Intervention / Treatment
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* Drug: Nicorandil
* Drug: normal saline


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Acute ST Segment Elevation Myocardial Infarction (ASTEMI) defined as typical chest pain lasting >30min within the previous 12 h, with a clear ST-segment elevation of >0.1millivolt(mV) in ≥2 contiguous electrocardiographic leads, and the value of troponin I(TNI) above the maximum peak in the normal range. Age20-80,All genders The first myocardial infarction, and there is no history of PCI therapy and coronary artery bypass grafting The infarct-related artery(IRA) is totally occlusive Blood pressure is higher than 90/60 millimeters of mercury（mmHg） The time from myocardial infarction onset to reach the hospital is less than 12 hs Successful interventional treatment, the residual stenosis of IRA is less than 30% , TIMI flow grade 3 Exclusion Criteria: kidney dysfunction (creatinine >2 mg/dl), History of previous liver disease, Cardiogenic shock, History of myocardial infarction (MI) History of coronary artery bypass grafting History of allergic response to drugs Right ventricular infarction Severe hypovolemia

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Nicorandil<br>Nicorandil for injection | Drug: Nicorandil<br>* All patients received antiplatelet agents (aspirin, ticagrelor) and heparin.Diagnostic coronary angiography (CAG) was performed via the right (or left) femoral artery or radial artery using the Seldinger method.The guidewire was passed into the culprit lesion. Subjects in the NicorandilGroup were then given 2 mg intracoronary nicorandil through the lesions via thrombus aspiration catheter, and an additional intracoronary dose of 2 mg nicorandil before stent implantation. A minimum 5-min interval occurred between the first and second doses of nicorandil to reduce adverse effects.<br>|
| Placebo Comparator: normal saline<br>normal saline | Drug: normal saline<br>* All patients received antiplatelet agents (aspirin, ticagrelor) and heparin.Diagnostic coronary angiography (CAG) was performed via the right (or left) femoral artery or radial artery using the Seldinger method.The guidewire was passed into the culprit lesion. Normal saline in the Placebo Group were then given 2 ml through the lesions via thrombus aspiration catheter,and an additional intracoronary dose of 2 ml before stent implantation. A minimum 5-min interval occurred between the first and second injection.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Primary composite endpoint (whether premature beats,atrial or ventricular tachycardia, atrial or ventricular fibrillation, and atrioventricular block appears;whether severity of chest pain is aggravated,and number of episodes chest pain) | The primary composite endpoint consisted of reperfusion-induced arrhythmia, worsening of chest pain, and no-reflow/slow reflow. In perioperative period,we will observe whether the reperfusion-induced arrhythmia including atrial or ventricular premature beats,atrial or ventricular tachycardia, atrial or ventricular fibrillation, and atrioventricular block appears;whether the severity of chest pain is aggravated,and the number of episodes of chest pain will be recorded for patients who complains of chest pain that lasted for at least 30 min within the 24 h following onset of MI;Whether the phenomenon of no-reflow/slow reflow appears.No-reflow and slow flow are diagnosed when the thrombolysis in myocardial infarction(TIMI) flow grade is 2 or lower,despite successful PCI such as balloon angioplasty or stent insertion. | 24hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| the combined outcome of TIMI frame count (cTFC) of CAG and ST resolution (STR) of ECG | The cTFC was measured according to the method of Gibson et al, to determine blood flow at the time of coronary angiography. The cine frame counts derived from the injection of contrast medium to the peripheral landmark were measured . In order to evaluate STR, the total sum of the ST segments elevation from the J point to the point reached 20ms later was calculated from the 12-lead ECG recorded before the start of reperfusion, and 90 min after the completion of reperfusion. The rate of improvement in ST elevation was classified as complete resolution (70% or more improvement) and no resolution (<70%). | 24hours | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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nicorandil, primary percutaneous coronary intervention, acute ST segment elevation myocardial infarction, thrombus aspiration