Microvascular Reperfusion Utilizing Sonothrombolysis in Acute Myocardial Infarction (MRUSMI TRIAL) (MRUSMI)

• ClinicalTrials.gov Identifier: NCT02170103
• Recruitment Status: Unknown
• First Posted: June 23, 2014
• Last Update Posted: June 23, 2014
• Sponsor: University of Nebraska
• Collaborators: InCor Heart Institute; VU University of Amsterdam
• Information provided by (Responsible Party): Thomas R. Porter, MD, University of Nebraska

Study Description

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. 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. Wilson Mathias, MD, will serve as the principal investigator for this site. The other is VU University Medical Center in Amsterdam, where Otto Kamp, MD, will serve as the principal investigator.

Condition or disease	Intervention/treatment	Phase
STEMI; Chest Pain,	Procedure: percutaneous intervention (PCI); Drug: Microbubbles; Procedure: Ultrasound	Phase 4

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 250 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Microvascular Reperfusion Utilizing Sonothrombolysis in Acute Myocardial Infarction (MRUSMI TRIAL)
• Study Start Date: May 2014
• Estimated Primary Completion Date: July 2015

Arms and Interventions

Arm	Intervention/treatment
Experimental: Ultrasound and microbubbles; 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.	Procedure: percutaneous intervention (PCI); Drug: Microbubbles; The agents will be divided into two separate doses (two vials per study), and mixed with approximately 29 milliliters of saline (approximately a 2.0-4.0% infusion). The first dilution will be administered pre PCI therapy, and the second dilution infused immediately post PCI. Since Optison is less stable in saline, an alternative approach will be to give the Optison as intermittent 0.1 milliliter boluses followed by 3-5 saline flushes over 10 seconds. The entire duration of each treatment before PCI will be up to 30 minutes depending on time constraints in getting to the catheterization laboratory, while the duration of treatment immediately after PCI will be 30 minutes.; Other Names: DEFINITY® (Perflutren Lipid Microsphere) manufactured by Lantheus Medical Imaging; OPTISON™ (Perflutren Protein-Type A Microspheres Injectable Suspension, USP) manufactured by General Electric Global Research; Procedure: Ultrasound; Intermittent high MI (Mechanical Index) impulses (0.8-1.4 MI; Frequency 1.0-1.7 MHz;pulse duration 4-44 microseconds) will be administered over the microvasculature where there are wall motion abnormalities and a perfusion defect using an imaging plane that best aligns itself with the risk area
Standard of care; Emergent PCI/antithrombotic/antiplatelet therapy with Echocardiogram to assess LVEF (Left Ventricular Ejection Fraction) and Aspirin, Plavix, or Direct Thrombin Inhibitor.	Procedure: percutaneous intervention (PCI)

Outcome Measures

Primary Outcome Measures :

1. Six month event free survival (EFS) [ Time Frame: 6 months ]
   The time from the start of treatment to first cardiac event or death as a first event. Cardiac events include, congestive heart failure, life threatening arrhythmias, and need for prophylactic defibrillator (primary and secondary).
2. Myocardial salvageability index [ Time Frame: Prior to hospital discharge (48-72 hours) ]
   The difference between extent of delayed enhancement by Gd MRI and the T2 weighted double or triple inversion spin echo assessment of risk area (defined above).
3. Frequency of left ventricular remodeling [ Time Frame: 6 month follow-up ]
   Defined as a 20% increase in end diastolic volume at the six month follow up biplane contrast enhanced echocardiogram compared to the pre-discharge contrast enhanced echocardiogram

Secondary Outcome Measures :

1. Safety of contrast in this setting [ Time Frame: at the time of procedure to 6 month follow-up ]
   Assessed by any alterations on oxygen saturation or hemodynamic effects acutely related to ultrasound contrast administration
2. Frequency of > 50% ST segment resolution by EKG at six hours post PCI. [ Time Frame: 6 hours post PCI ]
3. Area under the CPK (Creatine Phosphokinase) versus time curve [ Time Frame: at time of procedure ]
   Quantifies infarct size
4. Overall survival (OS) [ Time Frame: 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 ]
   Defined as the time from the start of randomized treatment to death from any cause.

Eligibility Criteria

• Ages Eligible for Study: 30 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• Patients presenting to participating centers with chest pain and EKG evidence of an acute STEMI (two contiguous leads with >0.1 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.

Contacts and Locations

Contacts

Contact: Thomas R Porter, MD; 402-559-7977; trporter@unmc.edu

Locations

Brazil

University of Sao Paulo Medical Center; Recruiting

Sao Paulo, Brazil

Contact: Wilson Mathias, Jr, MD (011) 98415-5556. wmathias@me.com

Netherlands

VU University Medical Center; Not yet recruiting

Amsterdam, Netherlands

Contact: Otto Kamp, MD

Sponsors and Collaborators

University of Nebraska

InCor Heart Institute

VU University of Amsterdam

Investigators

• Principal Investigator: Thomas R Porter, MD; University of NE Medical Center

More Information

Publications:

O'Gara PT, Kushner FG, Ascheim DD, Casey DE Jr, Chung MK, de Lemos JA, Ettinger SM, Fang JC, Fesmire FM, Franklin BA, Granger CB, Krumholz HM, Linderbaum JA, Morrow DA, Newby LK, Ornato JP, Ou N, Radford MJ, Tamis-Holland JE, Tommaso JE, Tracy CM, Woo YJ, Zhao DX; CF/AHA Task Force. 2013 ACCF/AHA guideline for the management of ST-elevation myocardial infarction: executive summary: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. Circulation. 2013 Jan 29;127(4):529-55. doi: 10.1161/CIR.0b013e3182742c84. Epub 2012 Dec 17.

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.

European Heart Rhythm Association; Heart Rhythm Society, Zipes DP, Camm AJ, Borggrefe M, Buxton AE, Chaitman B, Fromer M, Gregoratos G, Klein G, Moss AJ, Myerburg RJ, Priori SG, Quinones MA, Roden DM, Silka MJ, Tracy C, Smith SC Jr, Jacobs AK, Adams CD, Antman EM, Anderson JL, Hunt SA, Halperin JL, Nishimura R, Ornato JP, Page RL, Riegel B, Priori SG, Blanc JJ, Budaj A, Camm AJ, Dean V, Deckers JW, Despres C, Dickstein K, Lekakis J, McGregor K, Metra M, Morais J, Osterspey A, Tamargo JL, Zamorano JL; American College of Cardiology; American Heart Association Task Force; European Society of Cardiology Committee for Practice Guidelines. ACC/AHA/ESC 2006 guidelines for management of patients with ventricular arrhythmias and the prevention of sudden cardiac death: a report of the American College of Cardiology/American Heart Association Task Force and the European Society of Cardiology Committee for Practice Guidelines (Writing Committee to Develop Guidelines for Management of Patients With Ventricular Arrhythmias and the Prevention of Sudden Cardiac Death). J Am Coll Cardiol. 2006 Sep 5;48(5):e247-346.

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.

Galiuto L, Garramone B, Scarà 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.

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

• Responsible Party: Thomas R. Porter, MD, Professor of Medicine, University of Nebraska
• ClinicalTrials.gov Identifier: NCT02170103 History of Changes
• Other Study ID Numbers: MRUSMI TRIAL
• First Posted: June 23, 2014
• Last Update Posted: June 23, 2014
• Last Verified: June 2014

Keywords provided by Thomas R. Porter, MD, University of Nebraska:

segment elevation myocardial infarctions (STEMIs),; sonothrombolysis; reperfusion; percutaneous intervention (PCI),; antithrombotic therapy,; antiplatelet therapy,

Additional relevant MeSH terms:

Myocardial Infarction; Infarction; Chest Pain; Ischemia; Pathologic Processes; Necrosis; Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Pain; Neurologic Manifestations; Signs and Symptoms