Ticagrelor and Intracoronary Morphine in Patients Undergoing Primary Percutaneous Coronary Intervention

ST-Segment Elevation Myocardial Infarction Clinical Trial

Official title:

Effects of Ticagrelor and Intracoronary Morphine on Myocardial Salvage in Patients With ST-Segment Elevation Myocardial Infarction Undergoing Primary Percutaneous Coronary Intervention

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT01738100
• Other study ID #: 2012-08-010
• Status: Recruiting
• Phase: Phase 2
• First received: November 23, 2012
• Last updated: July 4, 2016
• Start date: September 2012
• Est. completion date: December 2016

Study information

• Verified date: October 2014
• Source: Samsung Medical Center
• Contact: Hyeon-Cheol Gwon, MD/PhD
• Phone: 82-2-3410-6653
• Email: hcgwon62[@]gmail.com
• Is FDA regulated: No
• Health authority: South Korea: Institutional Review Board
• Study type: Interventional

Clinical Trial Summary

A 2 by 2 factorial, multicenter, prospective, randomized, open-label, blinded endpoint trial. Patients undergoing primary PCI for STEMI will be eligible. Enrolled patients will be randomly assigned to the ticagrelor group or the clopidogrel group in a 1:1 ratio. After emergent coronary angiography, patients who have thrombolysis in myocardial infarction (TIMI) flow grade <2 in coronary angiogram will be randomized again, to either bolus intracoronary injection of morphine sulfate or saline in a 1:1 ratio. Randomization will be stratified by infarct location (anterior vs. non-anterior), and morphine use for pain control before study enroll (for only intracoronary morphine).

Description:

1.1. Ticagrelor versus Clopidogrel

1. In spite of timely and successful reperfusion with primary percutaneous coronary intervention (PCI), the mortality rate still remains high1 and substantial numbers of patients suffer from subsequent left ventricular dysfunction or heart failure after ST-segment elevation myocardial infarction (STEMI).

2. One of limitations of primary PCI is distal embolization and effective antiplatelet therapy is needed in patients with STEMI.

3. Clopidogrel is a representative P2Y12 receptor antagonist and has shown consistent efficacy in patients with acute coronary syndromes. However, clopidogrel is a prodrug and has to be converted to an active metabolite to inhibit P2Y12 receptor. Therefore, onset of effect is relatively slow, antiplatelet effect is moderate, and response to clopidogrel shows wide individual variability.

4. Ticagrelor is a new, direct, reversible P2Y12 receptor antagonist, which has rapid and potent antiplatelet effect. In patients who have an acute coronary syndrome with or without ST-segment elevation, treatment with ticagrelor as compared with clopidogrel significantly reduced the rate of death from vascular causes, myocardial infarction, or stroke without an increase in the rate of overall major bleeding.

5. However, there has been no data whether ticagrelor can reduce infarct size compared with clopidogrel in patients undergoing primary PCI.

1.2. Intracoronary morphine administration

1. Lethal reperfusion injury accounts for up to 50% of the final size of a myocardial infarct.5,6 Therefore, adjunctive therapy that is effective in preventing lethal reperfusion injury is needed to potentiate the benefits of primary PCI.

2. During the past few decades, a large number of animal studies demonstrated that commonly used opioids could provide cardioprotection against ischemia-reperfusion injury. Opioid-induced preconditioning or postconditioning mimics ischemic preconditioning or ischemic postconditioning.

3. Recent small clinical trial demonstrated the cardioprotective effect of remote ischemic preconditioning and morphine during primary PCI. But this study was small and did not demonstrate the separate effect of morphine-induced cardioprotection.

2. Study Objective

1. To investigate the effects of ticagrelor on myocardial infarct size in patients with STEMI undergoing primary PCI compared with clopidogrel

2. To investigate the effects of morphine-induced cardioprotection during primary PCI in patients with STEMI

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 100
• Est. completion date: December 2016
• Est. primary completion date: December 2016
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 20 Years and older

Eligibility

1. Inclusion criteria

• Subject must be at least 20 years of age.

• Patients undergoing primary PCI for STEMI

• Diagnosis of STEMI: ST-segment elevation >0.1 millivolt in =2 contiguous leads or (presumably) new left bundle branch block

• Presence of symptoms less than 12 hours

• Additional inclusion criteria for intracoronary morphine

• TIMI flow grade 0 or 1 of infarct related arteries

2. Exclusion Criteria:

• Known hypersensitivity or contraindication to study medications or contrast

• Female of childbearing potential, unless a recent pregnancy test is negative, who possibly plan to become pregnant any time after enrollment into this study.

• Rescue PCI after thrombolysis or facilitated PCI

• Cardiogenic shock or cardiopulmonary resuscitation before randomization

• Known chronic hepatic disease

• Known renal dysfunction (creatinine level 3.0mg/dL or dependence on dialysis).

• Decompensated chronic obstructive pulmonary disease or active asthma at inclusion

• Mechanical ventilation at inclusion

• Brain injury or intracranial hypertension

• Acute alcohol intoxication

• Known ulcerative colitis

• Active epilepsy

• Contraindications to undergo MRI imaging include any of the following

• A cardiac pacemaker or implantable defibrillator; any implanted or magnetically activated device; or any history indicating contraindication to MRI including claustrophobia or allergy to gadolinium

• Current use of oral anticoagulant

• An increased risk of bradycardia

• Sinus node dysfunction, atrioventricular dysfunction, or heart rate <40/min

• Patients receiving clopidogrel 300 mg or more before randomization

• One of followings

• history of intracranial bleeding

• intracranial tumor, arteriovenous malformation or aneurysm

• stroke within past 3 months

• Active bleeding of internal organ or bleeding diathesis

• Acute aortic dissection

Study Design

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

Related Conditions & MeSH terms

• Infarction
• Myocardial Infarction
• ST-Segment Elevation Myocardial Infarction

Intervention

Drug:
• Ticagrelor

• Clopidogrel

• Morphine Sulfate

• Saline

Locations

Country	Name	City	State
Korea, Republic of	Samsung Medical Center	Seoul	Gang nam-Gu, Ilwon-Dong

Sponsors (1)

Lead Sponsor	Collaborator
Hyeon-Cheol Gwon

Country where clinical trial is conducted

Korea, Republic of, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Myocardial infarct size measured by magnetic resonance imaging (MRI) at 3-5 days after the index procedure		Post-PCI 3-5 days	No
Secondary	Rate of complete ST-segment resolution on ECG obtained 30 minutes after the procedure		30 min after completion of PCI	No
Secondary	Enzymatic Infarct size by creatine kinase-MB (area under curve)		1 month later	No
Secondary	Myocardial salvage index measured by MRI		Post-PCI 3-5 days	No
Secondary	Major adverse cardiac events (a composite of death, myocardial infarction, severe heart failure, or stent thrombosis)		1Month later	Yes
Secondary	The extent of microvascular obstruction measured by MRI		post-PCI 3-5days	No
Secondary	The number of segments with >75% of infarct transmurality measured by MRI		post-PCI 3-5 days	No
Secondary	The presence of myocardial hemorrhage measured by MRI		post-PCI 3-5 days	No