Ticagrelor Versus Clopidogrel in Left Ventricular Remodeling After ST-segment Elevation Myocardial Infarction (HEALING-AMI)

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

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.

Study Overview

• Status: Unknown
• Conditions: ST Elevation Myocardial Infarction
• Intervention / Treatment: Drug: Ticagrelor; Drug: Clopidogrel

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.

• Study Type: Interventional
• Enrollment (Anticipated): 326
• Phase: Phase 4

Contacts and Locations

Study Locations

• China
  • Bejing, China
    • Not yet recruiting
    • Chinese PLA General Hospital
    • Principal Investigator: Yundai Chen, MD.
• Korea, Republic of
  • Changwon, Korea, Republic of
    • Recruiting
    • Changwon Samsung Medical Center
    • Principal Investigator: Ju Hyeon Oh, MD
  • Chungju, Korea, Republic of
    • Recruiting
    • Chungbuk National University Hospital
    • Principal Investigator: Sang Yeub Lee, MD.
  • Daegu, Korea, Republic of
    • Recruiting
    • Kyungpook National University Hospital
    • Principal Investigator: Jang Hoon Lee, MD
  • Daejeon, Korea, Republic of
    • Recruiting
    • Chungnam National University Hospital
    • Principal Investigator: Jae-Hyeong Park, MD.
  • Korea, Korea, Republic of, 660-702
    • Recruiting
    • Gyeongsang National University Hospital
    • Principal Investigator: Yongwhi Park, MD.,PhD.
    • Principal Investigator: Young-Hoon Jeong, MD.,PhD.
  • Seoul, Korea, Republic of
    • Recruiting
    • Kyung Hee University Hospital
    • Principal Investigator: Won Kim, MD.
  • Ulsan, Korea, Republic of
    • Recruiting
    • Ulsan University Hospital
    • Principal Investigator: Eun-Seok Shin, MD.
  • Yangsan, Korea, Republic of
    • Recruiting
    • Pusan National University Yangsan Hospital
    • Principal Investigator: Jeong Su Kim, MD.
  • CHONRANAM-Do
    • Gwangju, CHONRANAM-Do, Korea, Republic of
      • Recruiting
      • Chonnam National University Hospital
      • Contact: Young-Joon Hong, MD, PhD
  • Gyeongki-do
    • Bundang, Gyeongki-do, Korea, Republic of
      • Recruiting
      • Seoul National University Bundang Hospital
      • Contact: Jeong-Won Suh, MD, PhD
• Singapore
  • Singapore, Singapore
    • Active, not recruiting
    • National University Heart Centre

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Ticagrelor and Clopidogrel.; 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; Ticagrelor 180 mg as a loading dose and 90 mg twice daily as a maintenance dose; Other Names: Brillinta
Active Comparator: Clopidogrel; 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; Clopidogrel 600 mg as a loading dose and 75 mg once daily as a maintenance dose.; Other Names: Plavix

What is the study measuring?

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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Post-PCI angiographic perfusion indicators: TIMI flow grade, myocardial blush grade, corrected TIMI frame count		Just after primary PCI
EKG change: ST-segment elevation resolution (%), complete ST-segment resolution	complete ST-segment resolution: ST-segment resolution ≥70%	Baseline, 60 minutes after the PCI.
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	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.	6 months after the events
Cardiac MRI (Substudy): LV remodeling index	Measured at A*STAR-NUS Clinical Imaging Research Centre, Singapore	Three days and 6 months after the events
Level of inflammatory markers (Substudy)		During hospitalization and at 1 month after the events

Collaborators and Investigators

• Sponsor: Gyeongsang National University Hospital
• Collaborators: Chonnam National University Hospital; Chinese PLA General Hospital; Ulsan University Hospital; Seoul National University Bundang Hospital; Kyungpook National University Hospital; Pusan National University Yangsan Hospital; Chungnam National University Hospital; Chungbuk National University Hospital; National University Heart Centre, Singapore; Kyunghee University Medical Center; Samsung Changwon Hospital
• Investigators: Principal Investigator: Yongwhi Park, MD., PhD., Gyeongsang National University Hospital; Principal Investigator: Young-Hoon Jeong, MD.,PhD., Gyeongsan National University Hospital

Publications and helpful links

General Publications

• 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.
• 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.

Study record dates

Study Major Dates

• Study Start: October 1, 2014
• Primary Completion (Anticipated): June 1, 2017
• Study Completion (Anticipated): December 1, 2017

Study Registration Dates

• First Submitted: August 20, 2014
• First Submitted That Met QC Criteria: August 21, 2014
• First Posted (Estimate): August 25, 2014

Study Record Updates

• Last Update Posted (Estimate): November 15, 2016
• Last Update Submitted That Met QC Criteria: November 14, 2016
• Last Verified: November 1, 2016

More Information

Terms related to this study

• Keywords: Ticagrelor; Platelet reactivity; Left ventricular remodeling; ST elevation myocardial infarction.
• Additional Relevant MeSH Terms: Ischemia; Pathologic Processes; Necrosis; Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Pathological Conditions, Anatomical; Myocardial Infarction; Infarction; ST Elevation Myocardial Infarction; Ventricular Remodeling; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Platelet Aggregation Inhibitors; Purinergic P2Y Receptor Antagonists; Purinergic P2 Receptor Antagonists; Purinergic Antagonists; Purinergic Agents; Ticagrelor; Clopidogrel
• Other Study ID Numbers: D5130C00138

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO