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Ticagrelor and Intracoronary Morphine in Patients Undergoing Primary Percutaneous Coronary Intervention

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01738100
Recruitment Status : Unknown
Verified October 2014 by Hyeon-Cheol Gwon, Samsung Medical Center.
Recruitment status was:  Recruiting
First Posted : November 30, 2012
Last Update Posted : July 6, 2016
Information provided by (Responsible Party):
Hyeon-Cheol Gwon, Samsung Medical Center

Brief 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).

Condition or disease Intervention/treatment Phase
ST-Segment Elevation Myocardial Infarction Drug: Ticagrelor Drug: Clopidogrel Drug: Morphine Sulfate Drug: Saline Phase 2

Detailed 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

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 100 participants
Allocation: Randomized
Intervention Model: Factorial Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Effects of Ticagrelor and Intracoronary Morphine on Myocardial Salvage in Patients With ST-Segment Elevation Myocardial Infarction Undergoing Primary Percutaneous Coronary Intervention
Study Start Date : September 2012
Estimated Primary Completion Date : December 2016
Estimated Study Completion Date : December 2016

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Heart Attack

Arm Intervention/treatment
Experimental: Ticagrelor + Intracoronary Morphine
180 mg loading pre-PCI followed by 90 mg bid for 5 days. Intracoronary Morphine Sulfate 3 mg + Saline 3 ml mix.
Drug: Ticagrelor
Other Name: Brilinta

Drug: Morphine Sulfate
Other Name: Morphine

Experimental: Ticagrelor + Intracoronary Saline
180 mg loading pre-PCI followed by 90 mg bid for 5 days. Saline 3 ml intracoronary injection.
Drug: Ticagrelor
Other Name: Brilinta

Drug: Saline
Other Name: Normal Saline

Experimental: Clopidogrel + Intracoronary Morphine
600 mg loading pre-PCI followed by 75 mg qd for 5 days. Morphine Sulfate 3 mg + Saline 3 ml mix intracoronary injection.
Drug: Clopidogrel
Other Name: Plavix

Drug: Morphine Sulfate
Other Name: Morphine

Active Comparator: Clopidogrel + Intracoronary Saline
600 mg loading pre-PCI followed by 75 mg qd for 5 days. Saline 3 ml intracoronary injection.
Drug: Clopidogrel
Other Name: Plavix

Drug: Saline
Other Name: Normal Saline

Primary Outcome Measures :
  1. Myocardial infarct size measured by magnetic resonance imaging (MRI) at 3-5 days after the index procedure [ Time Frame: Post-PCI 3-5 days ]

Secondary Outcome Measures :
  1. Rate of complete ST-segment resolution on ECG obtained 30 minutes after the procedure [ Time Frame: 30 min after completion of PCI ]
  2. Enzymatic Infarct size by creatine kinase-MB (area under curve) [ Time Frame: 1 month later ]
  3. Myocardial salvage index measured by MRI [ Time Frame: Post-PCI 3-5 days ]
  4. Major adverse cardiac events (a composite of death, myocardial infarction, severe heart failure, or stent thrombosis) [ Time Frame: 1Month later ]
  5. The extent of microvascular obstruction measured by MRI [ Time Frame: post-PCI 3-5days ]
  6. The number of segments with >75% of infarct transmurality measured by MRI [ Time Frame: post-PCI 3-5 days ]
  7. The presence of myocardial hemorrhage measured by MRI [ Time Frame: post-PCI 3-5 days ]

Information from the National Library of Medicine

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Ages Eligible for Study:   20 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
  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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01738100

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Contact: Hyeon-Cheol Gwon, MD/PhD 82-2-3410-6653
Contact: Joo-Yong Hahn, MD/PhD 82-2-3410-6653

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Korea, Republic of
Samsung Medical Center Recruiting
Seoul, Gang nam-Gu, Ilwon-Dong, Korea, Republic of, 135-710
Contact: Hyeon-Cheol Gwon, PhD    82-2-3410-6653   
Contact: Joo-Yong Hahn, PhD    82-2-3410-6653   
Sponsors and Collaborators
Hyeon-Cheol Gwon
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Principal Investigator: Hyeon-Cheol Gwon, MD/PhD Samsung Medical Center
Publications automatically indexed to this study by Identifier (NCT Number):
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Responsible Party: Hyeon-Cheol Gwon, Professor, Samsung Medical Center Identifier: NCT01738100    
Other Study ID Numbers: 2012-08-010
First Posted: November 30, 2012    Key Record Dates
Last Update Posted: July 6, 2016
Last Verified: October 2014
Additional relevant MeSH terms:
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Myocardial Infarction
ST Elevation Myocardial Infarction
Pathologic Processes
Myocardial Ischemia
Heart Diseases
Cardiovascular Diseases
Vascular Diseases
Analgesics, Opioid
Central Nervous System Depressants
Physiological Effects of Drugs
Sensory System Agents
Peripheral Nervous System Agents
Platelet Aggregation Inhibitors
Purinergic P2Y Receptor Antagonists
Purinergic P2 Receptor Antagonists
Purinergic Antagonists
Purinergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action