Ticagrelor and Intracoronary Morphine in Patients Undergoing Primary Percutaneous Coronary Intervention

July 4, 2016 updated by: Hyeon-Cheol Gwon

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

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).

Study Overview

Status

Unknown

Conditions

Intervention / Treatment

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

Study Type

Interventional

Enrollment (Anticipated)

100

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Korea, Republic of
    • Gang nam-Gu, Ilwon-Dong
      • Seoul, Gang nam-Gu, Ilwon-Dong, Korea, Republic of, 135-710
        • Recruiting
        • Samsung Medical Center
        • Contact:
          • Hyeon-Cheol Gwon, PhD
          • Phone Number: 82-2-3410-6653
          • Email: hcgwon@skku.edu
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

20 years and older (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

  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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: RANDOMIZED
  • Interventional Model: FACTORIAL
  • Masking: NONE

Arms and Interventions

Participant Group / 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 Names:
  • Brilinta
Drug: Morphine Sulfate
Other Names:
  • 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 Names:
  • Brilinta
Drug: Saline
Other Names:
  • 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 Names:
  • Plavix
Drug: Morphine Sulfate
Other Names:
  • 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 Names:
  • Plavix
Drug: Saline
Other Names:
  • Normal Saline

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Myocardial infarct size measured by magnetic resonance imaging (MRI) at 3-5 days after the index procedure
Time Frame: Post-PCI 3-5 days
Post-PCI 3-5 days

Secondary Outcome Measures

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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Hyeon-Cheol Gwon

Investigators

  • Principal Investigator: Hyeon-Cheol Gwon, MD/PhD, Samsung Medical Center

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

September 1, 2012

Primary Completion (ANTICIPATED)

December 1, 2016

Study Completion (ANTICIPATED)

December 1, 2016

Study Registration Dates

First Submitted

November 23, 2012

First Submitted That Met QC Criteria

November 29, 2012

First Posted (ESTIMATE)

November 30, 2012

Study Record Updates

Last Update Posted (ESTIMATE)

July 6, 2016

Last Update Submitted That Met QC Criteria

July 4, 2016

Last Verified

October 1, 2014

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2012-08-010

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on ST-Segment Elevation Myocardial Infarction

Clinical Trials on Ticagrelor

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Czech Republic

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

Subscribe