Clinical trial NCT02410330: Therapeutic Use of Ultrasound in Acute Coronary Artery Disease
Official title: Therapeutic Use of Ultrasound in Acute Coronary Artery Disease
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Acute Myocardial Infarction
Keywords: Therapeutic ultrasound
Angiographic recanalization rate
Salvagability index
Sonothrombolysis
Lead sponsor: University of Sao Paulo General Hospital
Sponsor class: OTHER
Collaborators: name: University of Nebraska
First posted: 2015-04-07
Enrollment: 100
Sex: ALL
Minimum age (years): 30
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: CASE_CONTROL
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Patients with acute ST elevation myocardial infarction (STEMI) with less than 12 hours of chest pain onset, eligible for emergent percutaneous coronary intervention therapy.

Brief summary: In acute coronary artery disease, pre-clinical studies have indicated that, during a continuous infusion of intravenous perfluorocarbon containing microbubbles, the ultrasonic power delivered from a diagnostic ultrasound transducer is capable of restoring microcirculatory flow and improving epicardial recanalization rates obtained by conventional therapy, a process known by Sonothrombolysis. The investigators proposed to examine the feasibility, safety and efficacy of such an ultrasound guided approach in 100 patients with ST segment elevation myocardial infarction (STEMI).

Detailed description: In acute coronary artery disease, pre-clinical studies have indicated that, during a continuous infusion of intravenous perfluorocarbon containing microbubbles, the ultrasonic power delivered from a diagnostic ultrasound transducer is capable of restoring microcirculatory flow and improving epicardial recanalization rates obtained by conventional therapy, a process known by Sonothrombolysis. Since both diagnostic ultrasound and intravenous infusions of microbubbles are a Class I indication to assess regional and global left ventricular function and risk area in patients with ST segment elevation myocardial infarction (STEMI). The investigators propose to examine the effectiveness of microvascular sonothrombolysis.

A total of 100 patients with acute STEMI will be randomized to receive diagnostic ultrasound guided high mechanical index (MI) impulses in different approaches applied within and outside the risk area during a continuous infusion of intravenous 3% Definity® or placebo. The different ultrasound regimens are: Group I - a custom designed high mechanical index (MI) impulses at 4-20 usec and \>1.0 MI designed for the 1.7 MHz S5-1 transducer; Group II - repeated diagnostic high MI impulses (all \<2 usec pulse duration; MI=1.0 whenever very low MI perfusion imaging detected microbubbles within the microvasculature; Group III (control), where a few limited diagnostic high MI impulses (n\<5 per patient) will be applied to assess myocadial perfusion before and after percutaneous coronary intervention (PCI). All patients will receive the conventional PCI approach, including 325 milligrams Aspirin, 600 milligrams Clopidogrel, and heparin bolus (5000 units), followed by primary PCI using glycoprotein 2b/3a inhibitors as anti-thrombotic agents using established protocols. Besides angiographic recanalization rates at the time of presentation to the catheterization laboratory, the patients will have a magnetic resonance exam performed at 72-96 hours post infarcton to quantify the myocardial salvagability index. Quantitative assessments of ejection fraction will be made at this time as well.Overall survival (OS), defined as the time from the start of treatment to death from any cause, will be evaluated.Comparisons between the three groups will be made on door to dilation times, survival, angiographic recanalization rates (ARR) at initial angiography, and reduction in infarct size determined by the salvagability index (SI) at magnetic resonance imaging 72-96 hours post STEMI. Left ventricular function and perfusion parameters by echocardiography will also be evaluated during, at 72-96 hours and at 6 months in all subjects.

Eligibility criteria: Inclusion Criteria:

* Age ≥30 years with STEMI with less than 12 hours of chest pain onset.
* Eligible for emergent PCI therapy.
* No contraindications or hypersensitivities to ultrasound contrast agents

Exclusion Criteria:

* Known or suspected hypersensitivity to ultrasound contrast agent used for the study.
* Cardiogenic Shock.
* 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 or severe pulmonary hypertension.
* Patients who received thrombolytic therapy previously to enrollment.

Primary outcomes:
measure: Angiographic recanalization rate
timeFrame: At initial angiography
Secondary outcomes:
measure: Salvagability index
timeFrame: 72-96 hours post infarction
measure: Overall survival
timeFrame: 30 days post infarction
measure: Left ventricular function and perfusion parameters
timeFrame: 72-96 hours and at 6 months
Other outcomes:
Locations:
city: São Paulo
country: Brazil
facility: Heart Institute (InCor)
Study officials:
affiliation: Heart Institute - University of São Paulo Medical School
name: Wilson Mathias Jr, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Mathias W Jr, Tsutsui JM, Tavares BG, Fava AM, Aguiar MOD, Borges BC, Oliveira MT Jr, Soeiro A, Nicolau JC, Ribeiro HB, Chiang HP, Sbano JCN, Morad A, Goldsweig A, Rochitte CE, Lopes BBC, Ramirez JAF, Kalil Filho R, Porter TR; MRUSMI Investigators. Sonothrombolysis in ST-Segment Elevation Myocardial Infarction Treated With Primary Percutaneous Coronary Intervention. J Am Coll Cardiol. 2019 Jun 11;73(22):2832-2842. doi: 10.1016/j.jacc.2019.03.006. Epub 2019 Mar 17.
citation: Aguiar MOD, Tavares BG, Tsutsui JM, Fava AM, Borges BC, Oliveira MT Jr, Soeiro A, Nicolau JC, Ribeiro HB, Chiang HP, Sbano JCN, Goldsweig A, Rochitte CE, Lopes BBC, Ramirez JAF, Kalil Filho R, Porter TR, Mathias W Jr. Sonothrombolysis Improves Myocardial Dynamics and Microvascular Obstruction Preventing Left Ventricular Remodeling in Patients With ST Elevation Myocardial Infarction. Circ Cardiovasc Imaging. 2020 Apr;13(4):e009536. doi: 10.1161/CIRCIMAGING.119.009536. Epub 2020 Apr 21.
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.