Therapeutic Use of Ultrasound in Acute Coronary Artery Disease

Completed

• Conditions: Acute Myocardial Infarction
• Interventions: Procedure: Repeated diagnostic high mechanical index; Procedure: Therapeutic ultrasound with 20 usec

• Registration Number: NCT02410330
• Lead Sponsor: University of Sao Paulo General Hospital

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.

Study Timeline

• Study Start: 2014-05
• Study First Submitted: 2015-04-01
• Study First Submitted QC: 2015-04-01
• Study First Posted: 2015-04-07
• Primary Completion: 2020-01
• Study Completion: 2020-01
• Status Verified: 2021-11
• Last Update Submitted: 2021-11-24
• Last Update Posted: 2021-12-08

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 100

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.

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Group II	Repeated diagnostic high mechanical index	Patients with acute STEMI will receive intravenous infusion of microbubbles (3% Definity) with therapeutic ultrasound with repeated diagnostic high mechanical index impulses (all \<2 usec pulse duration; MI=1.0) whenever very low MI perfusion imaging detected microbubbles within the microvasculature. Treatment will be applied while patient waits for percutaneous coronary intervention. Treatment will continue after procedure untill complete a total of 60 minutes.
Group I	Therapeutic ultrasound with 20 usec	Patients with acute STEMI will receive intravenous infusion of microbubbles (3% Definity) with Therapeutic ultrasound with 20 usec: custom designed high mechanical index (MI) impulses at 4-20 usec and \>1.0 MI designed for the 1.7 MHz S5-1 transducer while waiting for percutaneous coronary intervention. Treatment will continue after procedure untill complete a total of 60 minutes.

Primary Outcome Measures

Name	Time	Method
Angiographic recanalization rate	At initial angiography	Percentage of patients with acute STEMI and open artery at initial angiography (TIMI I)

Secondary Outcome Measures

Name	Time	Method
Salvagability index	72-96 hours post infarction	Percentage of myocardium with viability within the risk area obtained by magnetic ressonance imaging
Overall survival	30 days post infarction	The time from the start of treatment to death from any cause
Left ventricular function and perfusion parameters	72-96 hours and at 6 months	left ventricular volumes, ejection fraction, longitudinal strain, diastolic function and infarct size by myocardial contrast echocardiography

Trial Locations

Locations (1)

Heart Institute (InCor); 🇧🇷 São Paulo, Brazil