ST Elevation Myocardial Infarction
Conditions
Keywords
ST elevation myocardial infarction., Ticagrelor, Left ventricular remodeling, Platelet reactivity
Brief summary
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
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.
Interventions
DRUGTicagrelor
Ticagrelor 180 mg as a loading dose and 90 mg twice daily as a maintenance dose
DRUGClopidogrel
Clopidogrel 600 mg as a loading dose and 75 mg once daily as a maintenance dose.
Sponsors
Chinese PLA General Hospital
Chungnam National University Hospital
Pusan National University Yangsan Hospital
National University Heart Centre, Singapore
Ulsan University Hospital
Kyungpook National University Hospital
Samsung Changwon Hospital
Kyunghee University Medical Center
Chungbuk National University Hospital
Chonnam National University Hospital
Seoul National University Bundang Hospital
Gyeongsang National University Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| LV remodeling index (%) | Interval change between baseline and 6 months after the index events | 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. |
| NT-proBNP level at 6 months | 6 months after the index events | — |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Absolute change of LVESVI, LVEDVI and LVEF | Interval change between baseline and 6 months after the index events | — |
| Prevalence of adverse LV remodeling | Interval change between baseline and 6 months after the index events | Adverse LV remodeling: a relative \> 20% increase in LVEDV seen at 6-month follow-up compared with the baseline during admission. |
| Level of platelet reactivity | At the time of PCI, 3 days and 1 month after the events | Measured by VerifyNow P2Y12 assay |
Other
| Measure | Time frame | Description |
|---|---|---|
| Post-PCI angiographic perfusion indicators: TIMI flow grade, myocardial blush grade, corrected TIMI frame count | Just after primary PCI | — |
| Level of inflammatory markers (Substudy) | During hospitalization and at 1 month after the events | — |
| EKG change: ST-segment elevation resolution (%), complete ST-segment resolution | Baseline, 60 minutes after the PCI. | complete ST-segment resolution: ST-segment resolution ≥70% |
| Level of hs-CRP | At the time of PCI, 1 month and 6 months after the events | — |
| Bleeding events based on BARC or PLATO definition | 6 months after the events | BARC definition for bleeding is defined as type 1, 2, 3 (3a, 3b and 3c), 4, and 5 (5a and 5b), according to the Bleeding Academic Research Consortium classification. * Type 1 (nuisance or superficial bleeding). * Type 2 (internal bleeding). * Type 3a (TIMI minor bleeding). * Type 3b (TIMI major bleeding). * Type 3c (life threatening bleeding). * Type 4 (CABG-related bleeding). * Type 5a (probable fatal bleeding). * Type 5b (definite fatal bleeding). Bleeding events pertaining to type 1 to 3a are considered as minor bleeding and those pertaining to type 3b to 5b as major bleeding. PLATO definition for bleeding * Major life-threatening bleeding. * Other major bleeding. * Minor bleeding. The case report form (CRF) collects the event history of bleeding during admission and at 1 month and 6 months. Occurrences of major, minor, and combined major and minor bleeding events will be compared between groups. |
| Cardiac MRI (Substudy): LV remodeling index | Three days and 6 months after the events | Measured at A\*STAR-NUS Clinical Imaging Research Centre, Singapore |
Countries
China, Singapore, South Korea
Contacts
Primary ContactYongwhi Park, MD.,PhD.
Backup ContactYoung-Hoon Jeong, MD.,PhD.
Outcome results
None listed