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

ST Elevation Myocardial Infarction Clinical Trial

— HEALING-AMI  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT02224534
• Other study ID #: D5130C00138
• Status: Recruiting
• Phase: Phase 4
• First received: August 20, 2014
• Last updated: November 14, 2016
• Start date: October 2014
• Est. completion date: December 2017

Study information

• Verified date: November 2016
• Source: Gyeongsang National University Hospital
• Contact: Yongwhi Park, MD.,PhD.
• Phone: +82-55-750-8059
• Email: angio2000[@]hanmail.net
• Is FDA regulated: No
• Health authority: Korea: Institutional Review Board
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 326
• Est. completion date: December 2017
• Est. primary completion date: June 2017
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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 Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Infarction
• Myocardial Infarction
• ST Elevation Myocardial Infarction
• Ventricular Remodeling

Intervention

Drug:
• Ticagrelor
Ticagrelor 180 mg as a loading dose and 90 mg twice daily as a maintenance dose
• Clopidogrel
Clopidogrel 600 mg as a loading dose and 75 mg once daily as a maintenance dose.

Locations

Country	Name	City	State
China	Chinese PLA General Hospital	Bejing
Korea, Republic of	Seoul National University Bundang Hospital	Bundang	Gyeongki-do
Korea, Republic of	Changwon Samsung Medical Center	Changwon
Korea, Republic of	Chungbuk National University Hospital	Chungju
Korea, Republic of	Kyungpook National University Hospital	Daegu
Korea, Republic of	Chungnam National University Hospital	Daejeon
Korea, Republic of	Chonnam National University Hospital	Gwangju	CHONRANAM-Do
Korea, Republic of	Gyeongsang National University Hospital	Korea
Korea, Republic of	Kyung Hee University Hospital	Seoul
Korea, Republic of	Ulsan University Hospital	Ulsan
Korea, Republic of	Pusan National University Yangsan Hospital	Yangsan
Singapore	National University Heart Centre	Singapore

Sponsors (12)

Lead Sponsor	Collaborator
Gyeongsang National University Hospital	Chinese PLA General Hospital, Chonnam National University Hospital, Chungbuk National University Hospital, Chungnam National University Hospital, Kyunghee University Medical Center, Kyungpook National University, National University Heart Centre, Singapore, Pusan National University Yangsan Hospital, Samsung Changwon Hospital, Seoul National University Bundang Hospital, Ulsan University Hospital

Countries where clinical trial is conducted

China,  Korea, Republic of,  Singapore, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Post-PCI angiographic perfusion indicators: TIMI flow grade, myocardial blush grade, corrected TIMI frame count		Just after primary PCI	No
Other	EKG change: ST-segment elevation resolution (%), complete ST-segment resolution	complete ST-segment resolution: ST-segment resolution =70%	Baseline, 60 minutes after the PCI.	No
Other	Level of hs-CRP		At the time of PCI, 1 month and 6 months after the events	No
Other	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	Yes
Other	Cardiac MRI (Substudy): LV remodeling index	Measured at A*STAR-NUS Clinical Imaging Research Centre, Singapore	Three days and 6 months after the events	No
Other	Level of inflammatory markers (Substudy)		During hospitalization and at 1 month after the events	No
Primary	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	No
Primary	NT-proBNP level at 6 months		6 months after the index events	No
Secondary	Absolute change of LVESVI, LVEDVI and LVEF		Interval change between baseline and 6 months after the index events	No
Secondary	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	No
Secondary	Level of platelet reactivity	Measured by VerifyNow P2Y12 assay	At the time of PCI, 3 days and 1 month after the events	No