SONOthrombolysis in Patients With an ST-segment Elevation Myocardial Infarction With fibrinoLYSIS (SONOSTEMI-LYSIS) Trial

Study Overview
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Brief Summary
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This study will assess the safety and feasibility of sonothrombolysis in the acute management of STEMI undergoing reperfusion therapy with systemic fibrinolysis as part of a pharmacoinvasive approach

Detailed Description
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This study is an open label, single-centre, randomized investigation of sonothrombolysis in 60 adult patients presenting with STEMI within 6 hours of the onset of clinical symptoms and receiving perfusion therapy with fibrinolysis as part of a pharmacoinvasive strategy. Patients will be randomized 2:1 to either adjunct treatment with sonothrombolysis or standard therapy alone according to the current American College of Cardiology/American Heart Association (ACC/AHA) or European Society of Cardiology (ESC) STEMI and PCI guidelines. All patients will receive serial echocardiography assessments during and after reperfusion with the final ECHO assessment at 90 days (+/- 7d) post reperfusion. Patient outcomes (medical records review) will be followed for 1 year after reperfusion.

Official Title
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SONOthrombolysis in Patients With an ST-segment Elevation Myocardial Infarction With fibrinoLYSIS (SONOSTEMI-LYSIS) Trial

Conditions
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ST Elevation Myocardial Infarction

Intervention / Treatment
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* Drug: Definity® with High Mechanical Index Ultrasound


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 fibrinolysis Have a high-risk STEMI ECG as defined as: >2mm ST-segment elevation in 2 anterior or lateral leads; or >2mm 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: 1. Isolated inferior STEMI without anterior ST-segment depression 2. Previous coronary bypass surgery 3. Cardiogenic shock 4. Known or suspected hypersensitivity to ultrasound contrast agent used for the study 5. Life expectancy of less than two months or terminally ill 6. Known bleeding diathesis or contraindication to glycoprotein 2b/3a inhibitors, anticoagulants, or aspirin 7. Known large right to left intracardiac shunts 8. Patient received another investigational medication or treatment within 30 days prior to presentation with STEMI

Ages Eligible for Study
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Minimum Age: 18 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
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Sonothrombolysis<br>Diagnostic myocardial contrast echocardiography with ultrasound contrast agent 5% Definity® plus Sonothrombolysis | Drug: Definity® with High Mechanical Index Ultrasound<br>* Sonothrombolysis; Echocardiographic imaging with intermittent diagnostic high mechanical index during an intravenous 5% Definity® infusion<br>|
| No Intervention: Standard of Care<br>Diagnostic myocardial contrast echocardiography with ultrasound contrast agent 5% Definity® | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Complete ST-Segment Resolution | ST-segment recovery as assessed by complete ST-segment resolution (>50%) | 90 minutes post TNK administration | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Frequency of rescue/urgent PCI | Frequency of rescue/urgent PCI following the administration of fibrinolysis. | approximately 3-24 hours post TNK administration | 
| ST-segment resolution (>50%) | ST-segment resolution (>50%) following a pharmacoinvasive approach at  30 minutes post PCI as assessed by the worst lead on electrocardiogram | approximately 30 minutes post TNK administration | 
| ST-segment resolution (continuous) | ST-segment resolution (continuous) following a pharmacoinvasive approach at  30 minutes post PCI as assessed by the worst lead on electrocardiogram | approximately 30 minutes post TNK administration | 
| Left ventricular ejection fraction | Left ventricular ejection fraction by ECHO (Simpson method) assessed on Day 1 (pre reperfusion), Day 3 +/-2d (hospital discharge), and Day 90 +/-2d after infarction. | Day 1 (pre reperfusion), Day 3 +/-2d (hospital discharge), and Day 90 +/-2d after infarction. | 
| Wall motion score index (WMSI) | Wall motion score index (WMSI) by ECHO assessed on Day 1 (pre reperfusion), Day 3 +/-2d (hospital discharge), and Day 90 +/-2d after infarction. Each of the 17 LV segments is classified as: 1 normal 2.hypokinetic 3.akinetic 4.dyskinetic The WMS index is the sum of the scores divided by the number of segments. Usually 17, but if a segment cannot be classified, the sum is divided by the number of readable segments. Minimum value is 1 : all segments are normal - best outcome Maximum value is 4: all segments are dyskinetic - worst outcome | Day 1 (pre reperfusion), Day 3 +/-2d (hospital discharge), and Day 90 +/-2d after infarction. | 
| Microvascular perfusion score index (MPSI) | Microvascular perfusion score index (MPSI) by ECHO assessed on Day 1 (pre reperfusion), Day 3 +/-2d (hospital discharge), and Day 90 +/-2d after infarction Each of the 17 LV segments is classified as: normal, contrast replenishment within 4 seconds mildly reduced, contrast replenishment takes longer than 4 seconds no contrast replenishment over 10 seconds The MPSI index is the sum of the scores divided by the number of segments. Usually 17, but if a segment cannot be classified, then the sum is divided by the number of readable segments Minimum value is 1 : all segments are normal - best outcome Maximum value is 3: all segments are not perfused - worst outcome | Day 1 (pre reperfusion), Day 3 +/-2d (hospital discharge), and Day 90 +/-2d after infarction. | 
| Global Longitudinal Strain (GLS) | Global Longitudinal Strain (GLS) by ECHO assessed on Day 1 (pre reperfusion), Day 3 +/-2d (hospital discharge), and Day 90 +/-2d after infarction GLS is measured using speckle tracking imaging (Epiq, Philips). The scale is - % which means percentage of longitudinal shortening of myocardial segments. Similar to the WMSI, GLS is calculated by dividing the sum of the longitudinal strain measurements in the myocardial segments segments by the number of segments which can be assessed by speckle tracking (18 when all segments in all 3 apical views can be analysed. The lower the absolute strain value the worse the LV function. | Day 1 (pre reperfusion), Day 3 +/-2d (hospital discharge), and Day 90 +/-2d after infarction. | 
| QRS Score | Selvester QRS Scoring System, assessed on Day 3 +/-2d (hospital discharge) ECG. Minimum score 0, Maximum score 32. Higher score indicates worse outcome. | Day 3 +/-2d (hospital discharge) |