Sonothrombolysis in Patients With STEMI

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

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.

Study Overview

• Status: Completed
• Conditions: ST-segment Elevation Myocardial Infarction
• Intervention / Treatment: Drug: Definity, (Lipid Microspheres) Intravenous Suspension; Device: Myocardial Contrast Echocardiography; Procedure: Repurfusion therapy with PPCI

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.

• Study Type: Interventional
• Enrollment (Actual): 15
• Phase: Phase 2

Contacts and Locations

Study Locations

• Canada
  • Alberta
    • Edmonton, Alberta, Canada
      • Mazankowski Alberta Heart Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 30 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

EXPERIMENTAL: 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)

Drug: 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; Device: 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; Procedure: Repurfusion therapy with PPCI; Patients will receive reperfusion therapy with PPCI as standard of care

What is the study measuring?

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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Allergic Reaction to Definity®	Number of participants who recorded any allergic reaction to Definity	Day 1, Day 3±2, 3 month Follow Up
Number of Participants With Vasospasm in Culprit Coronary Artery	Number of participants who recorded any vasospasm due to high impulse ultrasound	Day 1
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	Day 1, Day 3±2, 3 month Follow Up

Collaborators and Investigators

• Sponsor: Harald Becher
• Collaborators: Alberta Health services; University of Alberta
• Investigators: Principal Investigator: Harald Becher, University of Alberta

Publications and helpful links

General Publications

• Slikkerveer J, Kleijn SA, Appelman Y, Porter TR, Veen G, van Rossum AC, Kamp O. Ultrasound enhanced prehospital thrombolysis using microbubbles infusion in patients with acute ST elevation myocardial infarction: pilot of the Sonolysis study. Ultrasound Med Biol. 2012 Feb;38(2):247-52. doi: 10.1016/j.ultrasmedbio.2011.11.001. Epub 2011 Dec 16.
• Xie F, Lof J, Everbach C, He A, Bennett RM, Matsunaga T, Johanning J, Porter TR. Treatment of acute intravascular thrombi with diagnostic ultrasound and intravenous microbubbles. JACC Cardiovasc Imaging. 2009 Apr;2(4):511-8. doi: 10.1016/j.jcmg.2009.02.002.
• Roos ST, Juffermans LJ, van Royen N, van Rossum AC, Xie F, Appelman Y, Porter TR, Kamp O. Unexpected High Incidence of Coronary Vasoconstriction in the Reduction of Microvascular Injury Using Sonolysis (ROMIUS) Trial. Ultrasound Med Biol. 2016 Aug;42(8):1919-28. doi: 10.1016/j.ultrasmedbio.2016.03.032. Epub 2016 May 6.
• Mathias W Jr, Tsutsui JM, Tavares BG, Xie F, Aguiar MO, Garcia DR, Oliveira MT Jr, Soeiro A, Nicolau JC, Lemos PA Neto, Rochitte CE, Ramires JA, Kalil R Filho, Porter TR. Diagnostic Ultrasound Impulses Improve Microvascular Flow in Patients With STEMI Receiving Intravenous Microbubbles. J Am Coll Cardiol. 2016 May 31;67(21):2506-15. doi: 10.1016/j.jacc.2016.03.542.

Study record dates

Study Major Dates

• Study Start (ACTUAL): August 15, 2017
• Primary Completion (ACTUAL): October 3, 2019
• Study Completion (ACTUAL): October 3, 2019

Study Registration Dates

• First Submitted: March 15, 2017
• First Submitted That Met QC Criteria: March 21, 2017
• First Posted (ACTUAL): March 27, 2017

Study Record Updates

• Last Update Posted (ACTUAL): June 9, 2021
• Last Update Submitted That Met QC Criteria: May 13, 2021
• Last Verified: May 1, 2021

More Information

Terms related to this study

• Keywords: Sonothrombolysis, STEMI, PPCI, Microbubbles
• Additional Relevant MeSH Terms: Ischemia; Pathologic Processes; Necrosis; Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Myocardial Infarction; Infarction; ST Elevation Myocardial Infarction
• Other Study ID Numbers: ST2017-Pro00067953; Pro00067953 (OTHER: Health Ethics Research Board)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes