Microvascular Recovery With Ultrasound in Myocardial Infarction (MRUSMI) Post PCI Trial

NCT02170103 | Completed DMC

• 1 other identifier: 0300-17-FB
• Study Type: interventional
• Target: 50
• Locations: 2 countries
• Sites: 2

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.

Conditions

STEMI; Chest Pain

Keywords

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

Outcome Measures

Primary Outcomes (3)

• Six month event free survival (EFS)

  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).

  6 months

• Myocardial salvageability index

  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).

  Prior to hospital discharge (48-72 hours)

• Frequency of left ventricular remodeling

  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

  6 month follow-up

Secondary Outcomes (4)

• Safety of contrast in this setting

  at the time of procedure to 6 month follow-up

• Frequency of > 50% ST segment resolution by EKG at six hours post PCI.

  6 hours post PCI

• Area under the Creatine Phosphokinase (CPK) versus time curve

  at time of procedure

• Overall survival (OS)

  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

Study Arms (2)

Ultrasound and microbubbles

EXPERIMENTAL

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; Procedure: Ultrasound

Standard of care

OTHER

Emergent PCI/antithrombotic/antiplatelet therapy with Echocardiogram to assess Left Ventricular Ejection Fraction (LVEF) and Aspirin, Plavix, or Direct Thrombin Inhibitor.

Procedure: percutaneous intervention (PCI)

Interventions

percutaneous intervention (PCI) PROCEDURE

Successful PCI with the patent vessel and at least Thrombolysis in Myocardial Infarction (TIMI) 2 flow in the left anterior descending artery (LAD) post-PCI.

Standard of care; Ultrasound and microbubbles

Microbubbles DRUG

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.

Also known as: DEFINITY® (Perflutren Lipid Microsphere) manufactured by Lantheus Medical Imaging, OPTISON™ (Perflutren Protein-Type A Microspheres Injectable Suspension, USP) manufactured by General Electric Global Research

Ultrasound and microbubbles

Ultrasound PROCEDURE

Intermittent high Mechanical Index (MI) impulses (0.8-1.4 MI; Frequency 1.0-1.7 MegaHertz (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

Ultrasound and microbubbles

Eligibility Criteria

• Age: 30 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

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

Sponsors & Collaborators

• University of Nebraska: lead
• InCor Heart Institute: collaborator
• VU University of Amsterdam: collaborator

Study Sites (2)

University of Sao Paulo Medical Center

São Paulo, Brazil

Location

VU University Medical Center

Amsterdam, Netherlands

Location

Related Publications (6)

• 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. No abstract available.

  PMID: 23247303 BACKGROUND

• 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.

  PMID: 20510214 BACKGROUND

• 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. doi: 10.1016/j.jacc.2006.07.010. No abstract available.

  PMID: 16949478 BACKGROUND

• 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.

  PMID: 15936605 BACKGROUND

• 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.

  PMID: 18237684 BACKGROUND

• 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.

  PMID: 26109588 DERIVED

MeSH Terms

Conditions

ST Elevation Myocardial Infarction; Chest Pain

Interventions

Percutaneous Coronary Intervention; Microbubbles; perflutren; FS 069; High-Energy Shock Waves

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Endovascular Procedures; Vascular Surgical Procedures; Cardiovascular Surgical Procedures; Surgical Procedures, Operative; Minimally Invasive Surgical Procedures; Equipment and Supplies; Ultrasonic Waves; Sound; Radiation, Nonionizing; Radiation; Physical Phenomena

Study Officials

• Thomas R Porter, MD

  University of NE Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 13, 2014
• First Posted: June 23, 2014
• Study Start: September 16, 2018
• Primary Completion: March 3, 2023
• Study Completion: September 3, 2023
• Last Updated: October 31, 2023

Record last verified: 2023-10

Locations

BR (1); NL (1)