Clinical trial NCT02170103: Microvascular Recovery With Ultrasound in Myocardial Infarction (MRUSMI) Post PCI Trial
Official title: Effect of Diagnostic Echocardiogram on Microvascular Recovery Following Acute STEMI
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: STEMI
Chest Pain
Keywords: segment elevation myocardial infarctions (STEMIs),
sonothrombolysis
reperfusion
percutaneous intervention (PCI),
antithrombotic therapy,
antiplatelet therapy,
Lead sponsor: University of Nebraska
Sponsor class: OTHER
Collaborators: name: InCor Heart Institute
name: VU University of Amsterdam
First posted: 2014-06-23
Enrollment: 50
Sex: ALL
Minimum age (years): 30
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The investigators propose to test the effectiveness of a technique that uses a modified commercially available ultrasound system used for cardiac imaging, and a commercially available ultrasound contrast agent (microbubbles) to break up the blood clots that cause heart attacks. The ultrasound and microbubbles will be applied as soon as possible to patients presenting to the emergency department, after an EKG confirms that a heart attack is ongoing. Patients who provide emergent consent will be randomized to either conventional therapy for a heart attack, or conventional therapy and ultrasound with microbubbles. The ultrasound will be applied both before and after emergent heart catheterization, in order to break up the blood clots that are not only in the artery supplying the heart muscle, but also in the small branches (capillaries) that are fed by this artery. Following the randomized treatment, patients will be followed for the development of any complications (recurrent heart attack, heart failure, or need for defibrillator placement) as well as by echo and cardiac MRI to determine how much heart muscle was salvaged by the treatment.

Detailed description: The investigators propose to test the effectiveness of a technique that uses a modified commercially available ultrasound system used for cardiac imaging, and a commercially available ultrasound contrast agent (microbubbles) to break up the blood clots that cause heart attacks. The ultrasound and microbubbles will be applied as soon as possible to patients presenting to the emergency department, after an EKG confirms that a heart attack is ongoing. Patients who provide emergent consent will be randomized to either conventional therapy for a heart attack, or conventional therapy and ultrasound with microbubbles. The ultrasound will be applied both before and after emergent heart catheterization, in order to break up the blood clots that are not only in the artery supplying the heart muscle, but also in the capillaries that are fed by this artery. Following the randomized treatment, patients will be followed for the development of any complications (recurrent heart attack, heart failure, or need for defibrillator placement) as well as by echo and cardiac MRI to determine how much heart muscle was salvaged by the treatment. A total of 250 patients will be enrolled and followed at two different sites. Randomization will be stratified at each study site. The initial site enrolling patients will be University of Sao Paulo Medical School. The other is Vrije Universiteit (VU) University Medical Center in Amsterdam.

Eligibility criteria: Inclusion Criteria:

* Patients presenting to participating centers with chest pain and EKG evidence of an acute STEMI (two contiguous leads with \>0.1 millivolt (mV) ST elevation or \>0.1 ST depression in V2-V4) will be asked to participate. The inclusion criteria will be:

  1. Age ≥30 years.
  2. Eligible for emergent PCI/antithrombotic/antiplatelet therapy.
  3. Adequate apical and/or parasternal images by echocardiography.
  4. No contraindications or hypersensitivities to ultrasound contrast agents.

Exclusion Criteria:

1. Known or suspected hypersensitivity to ultrasound contrast agent used for the study.
2. Cardiogenic Shock
3. Life expectancy of less than two months or terminally ill.
4. Known severe cardiomyopathy.
5. Known bleeding diathesis or contraindication to glycoprotein 2b/3a inhibitors, anticoagulants, or aspirin
6. Known large right to left intracardiac shunts.

Primary outcomes:
measure: Six month event free survival (EFS)
timeFrame: 6 months
measure: Myocardial salvageability index
timeFrame: Prior to hospital discharge (48-72 hours)
measure: Frequency of left ventricular remodeling
timeFrame: 6 month follow-up
Secondary outcomes:
measure: Safety of contrast in this setting
timeFrame: at the time of procedure to 6 month follow-up
measure: Frequency of > 50% ST segment resolution by EKG at six hours post PCI.
timeFrame: 6 hours post PCI
measure: Area under the Creatine Phosphokinase (CPK) versus time curve
timeFrame: at time of procedure
measure: Overall survival (OS)
timeFrame: From date of randomization until the date of first documented progression or date of death from any cause, whichever comes first, assessed up to 120 months
Other outcomes:
Locations:
city: Sao Paulo
country: Brazil
facility: University of Sao Paulo Medical Center
city: Amsterdam
country: Netherlands
facility: VU University Medical Center
Study officials:
affiliation: University of NE Medical Center
name: Thomas R Porter, MD
role: PRINCIPAL_INVESTIGATOR
References:
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citation: Eitel I, Desch S, Fuernau G, Hildebrand L, Gutberlet M, Schuler G, Thiele H. Prognostic significance and determinants of myocardial salvage assessed by cardiovascular magnetic resonance in acute reperfused myocardial infarction. J Am Coll Cardiol. 2010 Jun 1;55(22):2470-9. doi: 10.1016/j.jacc.2010.01.049.
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citation: Ross AM, Gibbons RJ, Stone GW, Kloner RA, Alexander RW; AMISTAD-II Investigators. A randomized, double-blinded, placebo-controlled multicenter trial of adenosine as an adjunct to reperfusion in the treatment of acute myocardial infarction (AMISTAD-II). J Am Coll Cardiol. 2005 Jun 7;45(11):1775-80. doi: 10.1016/j.jacc.2005.02.061.
citation: Galiuto L, Garramone B, Scara A, Rebuzzi AG, Crea F, La Torre G, Funaro S, Madonna M, Fedele F, Agati L; AMICI Investigators. The extent of microvascular damage during myocardial contrast echocardiography is superior to other known indexes of post-infarct reperfusion in predicting left ventricular remodeling: results of the multicenter AMICI study. J Am Coll Cardiol. 2008 Feb 5;51(5):552-9. doi: 10.1016/j.jacc.2007.09.051.
citation: Wu J, Xie F, Lof J, Sayyed S, Porter TR. Utilization of modified diagnostic ultrasound and microbubbles to reduce myocardial infarct size. Heart. 2015 Sep;101(18):1468-74. doi: 10.1136/heartjnl-2015-307625. Epub 2015 Jun 24.