ST-segment Elevation Myocardial Infarction
Conditions
Keywords
Sonothrombolysis, STEMI, PPCI, Microbubbles
Brief summary
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
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.
Interventions
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
Myocardial contrast echocardiography will be applied before standard of care reperfusion therapy as well as prior to discharge and at 3 month follow up
PROCEDURERepurfusion therapy with PPCI
Patients will receive reperfusion therapy with PPCI as standard of care
Sponsors
Alberta Health services
University of Alberta
Harald Becher
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention 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.
Eligibility
Sex/Gender
ALL
Age
30 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Patients presenting with STEMI within 6 hours of symptom onset and: 1. Are expected to receive reperfusion therapy with primary PCI 2. 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 3. Age ≥30 years. 4. 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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Spontaneous Reperfusion | Day 1 | Spontaneous reperfusion as assessed by a pre PCI ECG complete ST-segment resolution (\>50%) (immediately prior to angiogram) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Left Ventricular Ejection Fraction (LVEF) by Echocardiography (ECHO) (Simpson Method) | Day 1, Day 3±2, 3 month Follow Up | assessed on day 1 (pre and post reperfusion), day 3±2 (discharge) and day 90±2 days after infarction |
| Number of Participants With Complete (>50%) ST-segment Resolution at 30 Minutes Post PCI | Day 1 | Complete ST-segment resolution as assessed by the worst lead on electrocardiogram (ECG core lab) |
| Wall Motion Score Index (WMSI) by ECHO | Day 1, Day 3±2 , 3 month Follow Up | 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. |
| Microvascular Perfusion Score Index (MPSI) by ECHO | Day 1, Day 3±2, 3 month Follow Up | 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. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Adverse Events | Day 1, Day 3±2, 3 month Follow Up | Number of participants who recorded any adverse events that as per protocol are not related to acute myocardial infarction |
| Number of Participants With Vasospasm in Culprit Coronary Artery | Day 1 | Number of participants who recorded any vasospasm due to high impulse ultrasound |
| Number of Participants With Allergic Reaction to Definity® | Day 1, Day 3±2, 3 month Follow Up | Number of participants who recorded any allergic reaction to Definity |
Countries
Canada
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Adult Patients With High Risk STEMI Adult patients presenting with high-risk STEMI will receive sonothrombolysis with Definity in addition to standard of care (reperfusion therapy with PPCI)
Definity, (Lipid Microspheres) Intravenous Suspension: 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
Myocardial Contrast Echocardiography: Myocardial contrast echocardiography will be applied before standard of care reperfusion therapy as well as prior to discharge and at 3 month follow up
Repurfusion therapy with PPCI: Patients will receive reperfusion therapy with PPCI as standard of care | 15 |
| Total | 15 |
Baseline characteristics
| Characteristic | Adult Patients With High Risk STEMI | — |
|---|---|---|
| Age, Continuous | 61.8 years STANDARD_DEVIATION 8 | — |
| Race and Ethnicity Not Collected | — | — Participants |
| Sex: Female, Male Female | 4 Participants | — |
| Sex: Female, Male Male | 11 Participants | — |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 15 |
| other Total, other adverse events | 6 / 15 |
| serious Total, serious adverse events | 3 / 15 |
Outcome results
Primary
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)
Time frame: Day 1
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Adult Patients With High Risk STEMI | Number of Participants With Spontaneous Reperfusion | 7 participants |
Primary
Number of Participants With Spontaneous Reperfusion
Spontaneous reperfusion as assessed by a pre PCI ECG complete ST-segment resolution (\>50%) (immediately prior to angiogram)
Time frame: Day 1
Population: for patients did not have a pre PCI ECG
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Adult Patients With High Risk STEMI | Number of Participants With Spontaneous Reperfusion | 2 participants |
Secondary
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
Time frame: Day 1, Day 3±2, 3 month Follow Up
Population: EF
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Adult Patients With High Risk STEMI | Left Ventricular Ejection Fraction (LVEF) by Echocardiography (ECHO) (Simpson Method) | EF at 3 months | 54.9 % ejection fraction | Standard Deviation 10.6 |
| Adult Patients With High Risk STEMI | Left Ventricular Ejection Fraction (LVEF) by Echocardiography (ECHO) (Simpson Method) | EF Day 3+/-2 | 54.6 % ejection fraction | Standard Deviation 9.9 |
| Adult Patients With High Risk STEMI | Left Ventricular Ejection Fraction (LVEF) by Echocardiography (ECHO) (Simpson Method) | EF Day 1 post PCI | 54.5 % ejection fraction | Standard Deviation 12.2 |
| Adult Patients With High Risk STEMI | Left Ventricular Ejection Fraction (LVEF) by Echocardiography (ECHO) (Simpson Method) | EF Day 1 pre PCI | 52.3 % ejection fraction | Standard Deviation 10.8 |
| Adult Patients With High Risk STEMI | Left Ventricular Ejection Fraction (LVEF) by Echocardiography (ECHO) (Simpson Method) | EF Day 1 admission | 51.5 % ejection fraction | Standard Deviation 11.6 |
Secondary
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.
Time frame: Day 1, Day 3±2, 3 month Follow Up
Population: Microvascular Perfusion Score Index (MPSI)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Adult Patients With High Risk STEMI | Microvascular Perfusion Score Index (MPSI) by ECHO | MPSI 3 months | 1.2 dimensionless | Standard Deviation 0.2 |
| Adult Patients With High Risk STEMI | Microvascular Perfusion Score Index (MPSI) by ECHO | MPSI Day 3+/-2 | 1.3 dimensionless | Standard Deviation 0.3 |
| Adult Patients With High Risk STEMI | Microvascular Perfusion Score Index (MPSI) by ECHO | MPSI Day 1 post PCI | 1.4 dimensionless | Standard Deviation 0.3 |
| Adult Patients With High Risk STEMI | Microvascular Perfusion Score Index (MPSI) by ECHO | MPSI Day 1 pre PCI | 1.6 dimensionless | Standard Deviation 0.2 |
| Adult Patients With High Risk STEMI | Microvascular Perfusion Score Index (MPSI) by ECHO | MPSI Day 1 admission | 1.7 dimensionless | Standard Deviation 0.3 |
Secondary
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)
Time frame: Day 1
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Adult Patients With High Risk STEMI | Number of Participants With Complete (>50%) ST-segment Resolution at 30 Minutes Post PCI | 14 participants |
Secondary
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.
Time frame: Day 1, Day 3±2 , 3 month Follow Up
Population: Wall Motion Score Index (WMSI)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Adult Patients With High Risk STEMI | Wall Motion Score Index (WMSI) by ECHO | WMSI 3 months | 1.4 dimensionless | Standard Deviation 0.4 |
| Adult Patients With High Risk STEMI | Wall Motion Score Index (WMSI) by ECHO | WMSI Day 3+/-2 | 1.5 dimensionless | Standard Deviation 0.3 |
| Adult Patients With High Risk STEMI | Wall Motion Score Index (WMSI) by ECHO | WMSI Day 1 post PCI | 1.6 dimensionless | Standard Deviation 0.3 |
| Adult Patients With High Risk STEMI | Wall Motion Score Index (WMSI) by ECHO | WMSI Day 1 pre PCI | 1.8 dimensionless | Standard Deviation 0.3 |
| Adult Patients With High Risk STEMI | Wall Motion Score Index (WMSI) by ECHO | WMSI Day 1 admission | 1.8 dimensionless | Standard Deviation 0.3 |
Other Pre-specified
Number of Participants With Adverse Events
Number of participants who recorded any adverse events that as per protocol are not related to acute myocardial infarction
Time frame: Day 1, Day 3±2, 3 month Follow Up
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Adult Patients With High Risk STEMI | Number of Participants With Adverse Events | 0 Participants |
Other Pre-specified
Number of Participants With Allergic Reaction to Definity®
Number of participants who recorded any allergic reaction to Definity
Time frame: Day 1, Day 3±2, 3 month Follow Up
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Adult Patients With High Risk STEMI | Number of Participants With Allergic Reaction to Definity® | 0 Participants |
Other Pre-specified
Number of Participants With Vasospasm in Culprit Coronary Artery
Number of participants who recorded any vasospasm due to high impulse ultrasound
Time frame: Day 1
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Adult Patients With High Risk STEMI | Number of Participants With Vasospasm in Culprit Coronary Artery | 0 Participants |