Clinical trial NCT02224534: Ticagrelor Versus Clopidogrel in Left Ventricular Remodeling After ST-segment Elevation Myocardial Infarction
Official title: High PlatElet Inhibition With TicAgrelor to Improve Left Ventricular RemodeLING in Patients With ST-segment ElevAtion Myocardial Infarction: the HEALING-AMI Trial.
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE4
Conditions: ST Elevation Myocardial Infarction
Keywords: ST elevation myocardial infarction.
Ticagrelor
Left ventricular remodeling
Platelet reactivity
Lead sponsor: Gyeongsang National University Hospital
Sponsor class: OTHER
Collaborators: name: Chinese PLA General Hospital
name: Chungnam National University Hospital
name: Pusan National University Yangsan Hospital
name: National University Heart Centre, Singapore
name: Ulsan University Hospital
name: Kyungpook National University Hospital
name: Samsung Changwon Hospital
name: Kyunghee University Medical Center
name: Chungbuk National University Hospital
name: Chonnam National University Hospital
name: Seoul National University Bundang Hospital
First posted: 2014-08-25
Enrollment: 326
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: LV remodeling index (%)
timeFrame: Interval change between baseline and 6 months after the index events
measure: NT-proBNP level at 6 months
timeFrame: 6 months after the index events
Secondary outcomes:
measure: Absolute change of LVESVI, LVEDVI and LVEF
timeFrame: Interval change between baseline and 6 months after the index events
measure: Prevalence of adverse LV remodeling
timeFrame: Interval change between baseline and 6 months after the index events
measure: Level of platelet reactivity
timeFrame: At the time of PCI, 3 days and 1 month after the events
Other outcomes:
measure: Post-PCI angiographic perfusion indicators: TIMI flow grade, myocardial blush grade, corrected TIMI frame count
timeFrame: Just after primary PCI
measure: EKG change: ST-segment elevation resolution (%), complete ST-segment resolution
timeFrame: Baseline, 60 minutes after the PCI.
measure: Level of hs-CRP
timeFrame: At the time of PCI, 1 month and 6 months after the events
measure: Bleeding events based on BARC or PLATO definition
timeFrame: 6 months after the events
measure: Cardiac MRI (Substudy): LV remodeling index
timeFrame: Three days and 6 months after the events
measure: Level of inflammatory markers (Substudy)
timeFrame: During hospitalization and at 1 month after the events
Locations:
city: Bejing
country: China
facility: Chinese PLA General Hospital
city: Gwangju
country: Korea, Republic of
facility: Chonnam National University Hospital
state: CHONRANAM-Do
city: Bundang
country: Korea, Republic of
facility: Seoul National University Bundang Hospital
state: Gyeongki-do
city: Changwon
country: Korea, Republic of
facility: Changwon Samsung Medical Center
city: Chungju
country: Korea, Republic of
facility: Chungbuk National University Hospital
city: Daegu
country: Korea, Republic of
facility: Kyungpook National University Hospital
city: Daejeon
country: Korea, Republic of
facility: Chungnam National University Hospital
city: Korea
country: Korea, Republic of
facility: Gyeongsang National University Hospital
city: Seoul
country: Korea, Republic of
facility: Kyung Hee University Hospital
city: Ulsan
country: Korea, Republic of
facility: Ulsan University Hospital
city: Yangsan
country: Korea, Republic of
facility: Pusan National University Yangsan Hospital
city: Singapore
country: Singapore
facility: National University Heart Centre
Study officials:
affiliation: Gyeongsang National University Hospital
name: Yongwhi Park, MD., PhD.
role: PRINCIPAL_INVESTIGATOR
affiliation: Gyeongsan National University Hospital
name: Young-Hoon Jeong, MD.,PhD.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Park Y, Koh JS, Lee JH, Park JH, Shin ES, Oh JH, Chun W, Lee SY, Bae JW, Kim JS, Kim W, Suh JW, Yang DH, Hong YJ, Chan MY, Kang MG, Park HW, Hwang SJ, Hwang JY, Ahn JH, Choi SW, Jeong YH; HEALING-AMI Investigators. Effect of Ticagrelor on Left Ventricular Remodeling in Patients With ST-Segment Elevation Myocardial Infarction (HEALING-AMI). JACC Cardiovasc Interv. 2020 Oct 12;13(19):2220-2234. doi: 10.1016/j.jcin.2020.08.007.
citation: Park Y, Choi SW, Oh JH, Shin ES, Lee SY, Kim J, Kim W, Suh JW, Yang DH, Hong YJ, Chan MY, Koh JS, Hwang JY, Park JH, Jeong YH; HEALING-AMI Trial Investigators. Rationale and Design of the High Platelet Inhibition with Ticagrelor to Improve Left Ventricular Remodeling in Patients with ST-Segment Elevation Myocardial Infarction (HEALING-AMI) Trial. Korean Circ J. 2019 Jul;49(7):586-599. doi: 10.4070/kcj.2018.0415. Epub 2019 Mar 22.