Sonothrombolysis in Patients With STEMI

Study Overview
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Brief Summary
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This study evaluates what effect sonothrombolysis may have on spontaneous reperfusion, microvascular obstruction, left ventricular function and infarct size in patients presenting with their first ST-segment Elevation Myocardial Infarction.

Detailed Description
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This is a prospective, single center, single-arm study that examines pre-procedural sonothrombolysis as an adjuvant to contemporary therapy in patients with ST-segment elevation myocardial infarction receiving PPCI.This study is to examine what effect adding emergent diagnostic ultrasound (DUS) guided high mechanical index (HMI) impulses (sonothrombolysis), applied both before and after primary percutaneous coronary intervention (PPCI) during an intravenous commercially available microbubble infusion (Definity), have on spontaneous reperfusion (i.e. pre PCI coronary artery patency rates), microvascular obstruction, left ventricular function and infarct size in patients presenting with their first ST-segment Elevation Myocardial Infarction. Patients will immediately receive an intravenous infusion of commercially available ultrasound contrast agent (Definity). After starting the infusion, myocardial contrast echocardiography will be performed. 4-, 2- and 3-chamber views will be recorded to document the size of the perfusion defect. Loops of 15 cardiac cycles will be recorded using low mechanical index (MI) ultrasound with a 'flash' delivered after the second cardiac cycle of the loop. The flash is a short impulse of HMI ultrasound which is transmitted to destroy the ultrasound contrast in the myocardium and then to assess the replenishment of myocardial contrast. These recordings will also be used to assess regional wall motion as well as the LV volumes and ejection fraction. Immediately after the diagnostic ultrasound, the therapeutic ultrasound will start using the same transducer by applying multiple HMI ultrasound impulses. The HMI are the same as those which are used for assessment of myocardial perfusion in diagnostic ultrasound. These pulses will be applied in the apical 4-, 2-, and 3-chamber views to the apical windows that contained the risk area. The intervals between HMI impulses will vary from 5 to 15 s depending on the time required for myocardial contrast replenishment. Diagnostic echocardiography will also be scheduled prior to discharge (Day2) and 90 days post procedure. If this study is successful, a larger study will be designed in order to collect the evidence for using contrast ultrasound for treatment of myocardial infarction in clinical practice.

Official Title
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Sonothrombolysis in Patients With an ST-segment Elevation Myocardial Infarction. A Prospective Single-arm Study.

Conditions
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ST-segment Elevation Myocardial Infarction

Intervention / Treatment
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* Drug: Definity, (Lipid Microspheres) Intravenous Suspension
* Device: Myocardial Contrast Echocardiography
* Procedure: Repurfusion therapy with PPCI


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients presenting with STEMI within 6 hours of symptom onset and: Are expected to receive reperfusion therapy with primary PCI Have a high-risk STEMI ECG defined as: ≥2mm ST-segment elevation in 2 anterior or lateral leads; or ≥2 mm ST-segment elevation in 2 inferior leads coupled with ST segment depression in 2 contiguous anterior leads for a total ST-segment deviation of ≥4mm Age ≥30 years. Adequate apical and/or parasternal images by echocardiography Exclusion Criteria: Isolated inferior STEMI without anterior ST-segment depression Previous coronary bypass surgery Cardiogenic shock Known or suspected hypersensitivity to ultrasound contrast agent used for the study Life expectancy of less than two months or terminally ill. Known bleeding diathesis or contraindication to glycoprotein 2b/3a inhibitors, anticoagulants, or aspirin Known large right to left intracardiac shunts.

Ages Eligible for Study
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Minimum Age: 30 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Interventional Model Description: This clinical study is a prospective single-center, single-arm investigation of sonothrombolysis in adult patients presenting with high-risk STEMI within 6 hrs of the onset of clinical symptoms and receiving reperfusion therapy with PCI. All patients will receive standard therapy. Patients will immediately receive an iv infusion of commercially available ultrasound contrast agent (Definity) and myocardial contrast echocardiography will be performed to document the size of the perfusion defect. Loops of 15 cardiac cycles will be recorded using low mechanical index (MI) ultrasound. These recordings will also be used to assess regional wall motion as well as LV volumes and ejection fraction. Immediately after the diagnostic ultrasound, the therapeutic ultrasound will start using the same transducer by applying multiple high MI ultrasound impulses. These pulses will be applied to the apical windows that contained the risk area. The intervals between HMI impulses will vary from 5 to 15 s.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Adult patients with high risk STEMI<br>Adult patients presenting with high-risk STEMI will receive sonothrombolysis with Definity in addition to standard of care (reperfusion therapy with PPCI) | Drug: Definity, (Lipid Microspheres) Intravenous Suspension<br>* Sonothrombolysis (High Impulse therapeutic ultrasound with infusion of ultrasound contrast agent Definity) will be applied before and after standard of care reperfusion therapy with PPCI<br>Device: Myocardial Contrast Echocardiography<br>* Myocardial contrast echocardiography will be applied before standard of care reperfusion therapy as well as prior to discharge and at 3 month follow up<br>Procedure: Repurfusion therapy with PPCI<br>* Patients will receive reperfusion therapy with PPCI as standard of care<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Spontaneous Reperfusion | Spontaneous reperfusion as assessed by a pre PCI ECG complete ST-segment resolution (>50%) (immediately prior to angiogram) | Day 1 | 
| Number of Participants With Spontaneous Reperfusion | Spontaneous reperfusion as assessed by a pre PCI TIMI 2-3 flow on diagnostic angiogram (immediately prior to angiogram) | Day 1 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Complete (>50%) ST-segment Resolution at 30 Minutes Post PCI | Complete ST-segment resolution as assessed by the worst lead on electrocardiogram (ECG core lab) | Day 1 | 
| Left Ventricular Ejection Fraction (LVEF) by Echocardiography (ECHO) (Simpson Method) | assessed on day 1 (pre and post reperfusion), day 3±2 (discharge) and day 90±2 days after infarction | Day 1, Day 3±2, 3 month Follow Up | 
| Wall Motion Score Index (WMSI) by ECHO | Mean Regional Wall Motion Score Index assessed on day 1 (pre and post reperfusion), day 3±2 (discharge) and 90±2 days after infarction. The wall motion score is determined by visual assessment of the regional wall LV wall motion in the three apical echocardiographic views. The wall motion score of LV segments is dimensionless: normal 1, hypokinetic 2, akinetic 3, dyskinetic 4. The wall motion score index is the sum of all segmental scores divided by the number of segments analyzed (scale 1-4). A wall motion score index of 1 is normal. The worse the wall motion score index the worse is the outcome. | Day 1, Day 3±2 , 3 month Follow Up | 
| Microvascular Perfusion Score Index (MPSI) by ECHO | Mean microvascular perfusion score index (MPSI) assessed on day 1 (pre and post reperfusion), day 3±2 (discharge) and 90±2 days after infarction The microvascular perfusion score is determined by visual assessment of the LV segments in the three apical echocardiographic views. The microvascular perfusion score of LV segments is dimensionless: normal 1, mildly reduced perfusion 2, no perfusion displayed 3. The microvascular perfusion score index score index is the sum of all segmental scores divided by the number of segments analyzed (scale 1 -3). A microvascular perfusion score index of 1 is normal. The worse the microvascular perfusion score index the worse is the outcome. | Day 1, Day 3±2, 3 month Follow Up | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Sonothrombolysis, STEMI, PPCI, Microbubbles