Ticagrelor and Intracoronary Morphine in Patients Undergoing Primary Percutaneous Coronary Intervention

This study is currently recruiting participants. (see Contacts and Locations)
Verified December 2013 by Samsung Medical Center
Sponsor:
Information provided by (Responsible Party):
Hyeon-Cheol Gwon, Samsung Medical Center
ClinicalTrials.gov Identifier:
NCT01738100
First received: November 23, 2012
Last updated: December 7, 2013
Last verified: December 2013
  Purpose

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 Intervention Phase
ST-Segment Elevation Myocardial Infarction
Drug: Ticagrelor
Drug: Clopidogrel
Drug: Morphine Sulfate
Drug: Saline
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Factorial Assignment
Masking: 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

Resource links provided by NLM:


Further study details as provided by Samsung Medical Center:

Primary Outcome Measures:
  • Myocardial salvage index measured by magnetic resonance imaging (MRI) at 3-5 days after the index procedure [ Time Frame: Post-PCI 3-5 days ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Rate of complete ST-segment resolution on ECG obtained 30 minutes after the procedure [ Time Frame: 30 min after completion of PCI ] [ Designated as safety issue: No ]
  • Enzymatic Infarct size by creatine kinase-MB (area under curve) [ Time Frame: 1 month later ] [ Designated as safety issue: No ]
  • Myocardial infarct size measured by MRI [ Time Frame: Post-PCI 3-5 days ] [ Designated as safety issue: No ]
  • Major adverse cardiac events (a composite of death, myocardial infarction, severe heart failure, or stent thrombosis) [ Time Frame: 1Month later ] [ Designated as safety issue: Yes ]
  • The extent of microvascular obstruction measured by MRI [ Time Frame: post-PCI 3-5days ] [ Designated as safety issue: No ]
  • The number of segments with >75% of infarct transmurality measured by MRI [ Time Frame: post-PCI 3-5 days ] [ Designated as safety issue: No ]
  • The presence of myocardial hemorrhage measured by MRI [ Time Frame: post-PCI 3-5 days ] [ Designated as safety issue: No ]

Estimated Enrollment: 100
Study Start Date: September 2012
Estimated Study Completion Date: December 2015
Estimated Primary Completion Date: December 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

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 salvage 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
  Eligibility

Ages Eligible for Study:   20 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria
  1. General 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
  2. Additional inclusion criteria for intracoronary morphine

    • TIMI flow grade 0 or 1 of infarct related arteries
  3. 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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01738100

Contacts
Contact: Hyeon-Cheol Gwon, MD/PhD 82-2-3410-6653 hcgwon62@gmail.com
Contact: Joo-Yong Hahn, MD/PhD 82-2-3410-6653 jyhahn@skku.edu

Locations
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    hcgwon@skku.edu   
Contact: Joo-Yong Hahn, PhD    82-2-3410-6653    jy.hahn@samsung.com   
Sponsors and Collaborators
Hyeon-Cheol Gwon
Investigators
Principal Investigator: Hyeon-Cheol Gwon, MD/PhD Samsung Medical Center
  More Information

No publications provided

Responsible Party: Hyeon-Cheol Gwon, Professor, Samsung Medical Center
ClinicalTrials.gov Identifier: NCT01738100     History of Changes
Other Study ID Numbers: 2012-08-010
Study First Received: November 23, 2012
Last Updated: December 7, 2013
Health Authority: South Korea: Institutional Review Board

Additional relevant MeSH terms:
Infarction
Myocardial Infarction
Ischemia
Pathologic Processes
Necrosis
Myocardial Ischemia
Heart Diseases
Cardiovascular Diseases
Vascular Diseases
Morphine
Clopidogrel
Ticagrelor
Analgesics, Opioid
Narcotics
Central Nervous System Depressants
Physiological Effects of Drugs
Pharmacologic Actions
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Central Nervous System Agents
Therapeutic Uses
Platelet Aggregation Inhibitors
Hematologic Agents
Purinergic P2Y Receptor Antagonists
Purinergic P2 Receptor Antagonists
Purinergic Antagonists
Purinergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on August 27, 2014