Clinical trial NCT03092089: Sonothrombolysis in Patients With STEMI
Official title: Sonothrombolysis in Patients With an ST-segment Elevation Myocardial Infarction. A Prospective Single-arm Study.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: ST-segment Elevation Myocardial Infarction
Keywords: Sonothrombolysis, STEMI, PPCI, Microbubbles
Lead sponsor: University of Alberta
Sponsor class: OTHER
Collaborators: name: Alberta Health services
name: University of Alberta
First posted: 2017-03-27
Enrollment: 15
Sex: ALL
Minimum age (years): 30
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
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.
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Number of Participants With Spontaneous Reperfusion
timeFrame: Day 1
measure: Number of Participants With Spontaneous Reperfusion
timeFrame: Day 1
Secondary outcomes:
measure: Number of Participants With Complete (>50%) ST-segment Resolution at 30 Minutes Post PCI
timeFrame: Day 1
measure: Left Ventricular Ejection Fraction (LVEF) by Echocardiography (ECHO) (Simpson Method)
timeFrame: Day 1, Day 3±2, 3 month Follow Up
measure: Wall Motion Score Index (WMSI) by ECHO
timeFrame: Day 1, Day 3±2 , 3 month Follow Up
measure: Microvascular Perfusion Score Index (MPSI) by ECHO
timeFrame: Day 1, Day 3±2, 3 month Follow Up
Other outcomes:
measure: Number of Participants With Allergic Reaction to Definity®
timeFrame: Day 1, Day 3±2, 3 month Follow Up
measure: Number of Participants With Vasospasm in Culprit Coronary Artery
timeFrame: Day 1
measure: Number of Participants With Adverse Events
timeFrame: Day 1, Day 3±2, 3 month Follow Up
Locations:
city: Edmonton
country: Canada
facility: Mazankowski Alberta Heart Institute
state: Alberta
Study officials:
affiliation: University of Alberta
name: Harald Becher
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.