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

Not Applicable

Completed

• Conditions: STEMI; Chest Pain
• Interventions: Procedure: percutaneous intervention (PCI); Drug: Microbubbles; Procedure: Ultrasound

• Registration Number: NCT02170103
• Lead Sponsor: University of Nebraska

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.

Study Timeline

• Study First Submitted: 2014-06-13
• Study First Submitted QC: 2014-06-19
• Study First Posted: 2014-06-23
• Study Start: 2018-09-16
• Primary Completion: 2023-03-03
• Study Completion: 2023-09-03
• Status Verified: 2023-10
• Last Update Submitted: 2023-10-27
• Last Update Posted: 2023-10-31

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 50

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Ultrasound and microbubbles	percutaneous intervention (PCI)	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.
Standard of care	percutaneous intervention (PCI)	Emergent PCI/antithrombotic/antiplatelet therapy with Echocardiogram to assess Left Ventricular Ejection Fraction (LVEF) and Aspirin, Plavix, or Direct Thrombin Inhibitor.
Ultrasound and microbubbles	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.
Ultrasound and microbubbles	Ultrasound	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.

Primary Outcome Measures

Name	Time	Method
Myocardial salvageability index	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).
Six month event free survival (EFS)	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).
Frequency of left ventricular remodeling	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

Name	Time	Method
Safety of contrast in this setting	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
Frequency of > 50% ST segment resolution by EKG at six hours post PCI.	6 hours post PCI	Frequency of \> 50% ST segment, (a key indicator for both myocardial ischaemia and necrosis if it goes up or down) resolution by EKG at six hours post PCI.
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	Defined as the time from the start of randomized treatment to death from any cause.
Area under the Creatine Phosphokinase (CPK) versus time curve	at time of procedure	Quantifies infarct size

Trial Locations

Locations (2)

VU University Medical Center; 🇳🇱 Amsterdam, Netherlands

University of Sao Paulo Medical Center; 🇧🇷 Sao Paulo, Brazil