Ticagrelor Versus Clopidogrel in Left Ventricular Remodeling After ST-segment Elevation Myocardial Infarction

Study Overview
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Brief Summary
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The purpose of the study is to evaluate the novel role of ticagrelor to improve long-term LV remodeling following ST-segment elevation myocardial infarction.

Detailed Description
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The investigators designed the HEALING-AMI study to compare the influence of ticagrelor (180 mg loading and 90 mg twice daily maintenance) vs. clopidogrel (600 mg loading and 75 mg daily maintenance) on long-term left ventricular (LV) remodeling measured by 3D echocardiography in STEMI patients undergoing primary PCI. The primary objective of the HEALING-AMI study is to demonstrate the novel role of long-term ticagrelor therapy in reducing the risk of LV remodeling,. The secondary objectives are to reveal the cross-talk between platelet and inflammatory process in ST-segment elevation myocardial infarction (STEMI) patients. Moreover, this study will determine whether the high platelet inhibition by ticagrelor culminate the protection of infarcted myocardium.

Official Title
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High PlatElet Inhibition With TicAgrelor to Improve Left Ventricular RemodeLING in Patients With ST-segment ElevAtion Myocardial Infarction: the HEALING-AMI Trial.

Conditions
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ST Elevation Myocardial Infarction

Intervention / Treatment
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* Drug: Ticagrelor
* Drug: Clopidogrel


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 18 years and older. First-time onset STEMI patients uneventfully treated with primary PCI within 12 hours of onset of symptom. Infarct-related artery with TIMI 0, 1, or 2 grade flow at the time of initial diagnostic angiography (before wire passage). proximal or mid-portion lesion of epicardial coronary artery. Exclusion Criteria: Previous history of myocardial infarction. Left bundle branch block on ECG at the time of screening. Cardiogenic shock at the time of randomization. Refractory ventricular arrhythmias or atrial fibrillation. New York Heart Association class IV congestive heart failure. Severe or malignant hypertension (SBP> 180 and/or DBP> 120 mmHg). Fibrinolytic therapy. History of hemorrhagic stroke. Intracranial neoplasm, arteriovenous malformation, or aneurysm. Ischemic stroke within 3 months prior to screening. Platelet count < 100,000/mm3 or hemoglobin < 10 g/dL. A need for oral anticoagulation therapy that cannot be safely discontinued for the duration of the study. Women who are known to be pregnant, have given birth within the past 90 days, or are breast-feeding. Unable to cooperate with protocol requirements and follow-up procedures. A history of P2Y12 receptor inhibitor pretreatment (at least prior 1 month). An increased risk of bradycardia. Concomitant therapy with a strong cytochrome P-450 3A inhibitor or inducer.

Ages Eligible for Study
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Minimum Age: 18 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: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Ticagrelor and Clopidogrel.<br>The patients assigned to the TICA group have loading dose of ticagrelor 180 mg just after the randomization, and then ticagrelor 90 mg twice daily during the study period. All patients also have aspirin 300 mg as a loading dose and 100 mg once daily as a maintenance dose. | Drug: Ticagrelor<br>* Ticagrelor 180 mg as a loading dose and 90 mg twice daily as a maintenance dose<br>* Other names: Brillinta;|
| Active Comparator: Clopidogrel<br>The patients assigned to the CLPD group have loading dose of clopidogrel 600 mg just after the randomization, and then clopidogrel 75 mg daily should be maintained during the study period. All patients also have aspirin 300 mg as a loading dose and 100 mg once daily as a maintenance dose. | Drug: Clopidogrel<br>* Clopidogrel 600 mg as a loading dose and 75 mg once daily as a maintenance dose.<br>* Other names: Plavix;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| LV remodeling index (%) | Real time 3D-echocardiography data sets will be analyzed with available 4D-LV Analysis software (e.g. TomTec Imaging Systems, Unterschleisheim, Germany) in the core lab. Left ventricular (LV) remodeling index: a relative change in LV end-diastolic volume (LVEDV) seen at 6-month follow-up compared with the baseline during admission. | Interval change between baseline and 6 months after the index events | 
| NT-proBNP level at 6 months |  | 6 months after the index events | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Absolute change of LVESVI, LVEDVI and LVEF |  | Interval change between baseline and 6 months after the index events | 
| Prevalence of adverse LV remodeling | Adverse LV remodeling: a relative > 20% increase in LVEDV seen at 6-month follow-up compared with the baseline during admission. | Interval change between baseline and 6 months after the index events | 
| Level of platelet reactivity | Measured by VerifyNow P2Y12 assay | At the time of PCI, 3 days and 1 month after the events | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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ST elevation myocardial infarction., Ticagrelor, Left ventricular remodeling, Platelet reactivity