NCT04732091

Brief Summary

Preclinical studies have demonstrated that high mechanical index (MI) impulses from a diagnostic ultrasound (DUS) transducer during an intravenous microbubble infusion (sonothrombolysis) can restore epicardial and microvascular flow in acute ST-segment elevation myocardial infarction (STEMI). The investigators propose to demonstrate the clinical effectiveness of sonothrombolysis in multiple centers and in a wide scenario of acute coronary syndromes.

Trial Health

47
At Risk

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Trial has exceeded expected completion date
Enrollment
540

participants targeted

Target at P75+ for all trials

Timeline
Completed

Started Feb 2022

Longer than P75 for all trials

Geographic Reach
2 countries

2 active sites

Status
unknown

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

January 22, 2021

Completed
10 days until next milestone

First Posted

Study publicly available on registry

February 1, 2021

Completed
1 year until next milestone

Study Start

First participant enrolled

February 17, 2022

Completed
2 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

February 1, 2024

Completed
2 years until next milestone

Study Completion

Last participant's last visit for all outcomes

February 1, 2026

Completed
Last Updated

October 10, 2023

Status Verified

October 1, 2023

Enrollment Period

2 years

First QC Date

January 22, 2021

Last Update Submit

October 6, 2023

Conditions

Keywords

UltrasoundSonothrombolysisContrast agentsMicrobubblesMicrovascular obstruction

Outcome Measures

Primary Outcomes (1)

  • Angiographic recanalization rate

    Percentage of patients with acute STEMI and open artery at initial angiography (TIMI I)

    At initial angiography

Secondary Outcomes (4)

  • Salvageability index

    72-96 hours and 3 months post infarction

  • Overall survival

    30 days post infarction

  • Cardiac remodeling

    72-96 hours, 30 days and at 6 months

  • Myocardial Mechanics

    72-96 hours, 30 days and at 6 months

Study Arms (5)

Subproject 1 - acute STEMI

Participants with acute STEMI will receive intravenous infusion of microbubbles (3% Definity) with therapeutic ultrasound with 4-20 usec and custom designed high mechanical index (MI) impulses (1.1 to 1.3 MI) designed for the 1.8 MHz S5-1 transducer while waiting for percutaneous coronary intervention. Treatment will continue after procedure until complete a total of 50 minutes.

Procedure: Therapeutic ultrasound with 20 usec

Subproject 2 - acute STEMI initially treated with fibrinolytic

Participants with acute STEMI initially treated with fibrinolytic therapy within 12 hours will receive intravenous infusion of microbubbles (3% Definity) with therapeutic ultrasound with 4-20 usec and custom designed high mechanical index (MI) impulses (1.1 to 1.3 MI) designed for the 1.8 MHz S5-1 transducer while waiting for percutaneous coronary intervention. A control group (PCI only) undergoing low MI (\<0.2) imaging only with limited (no more than 3) diagnostic high MI impulses to assess regional wall motion and microvascular perfusion before and after PCI; High MI will continue after PCI procedure until complete a total of 50 minutes.

Procedure: Therapeutic ultrasound with 20 usec

Subproject 3 - NSTEMI

Participants with NSTEMI or with high-risk unstable angina will receive intravenous infusion of microbubbles (3% Definity) with therapeutic ultrasound with 4-20 usec and custom designed high mechanical index (MI) impulses (1.1 to 1.3 MI) designed for the 1.8 MHz S5-1 transducer while waiting for percutaneous coronary intervention. A control group (PCI only) undergoing low MI (\<0.2) imaging only with limited (no more than 3) diagnostic high MI impulses to assess regional wall motion and microvascular perfusion before and after PCI. High MI will continue after PCI procedure until complete a total of 50 minutes.

Procedure: Therapeutic ultrasound with 20 usec

Subproject 4 - No reflow

Participants with acute STEMI will receive intravenous infusion of microbubbles (3% Definity) with therapeutic ultrasound with 4-20 usec and custom designed high mechanical index (MI) impulses (1.1 to 1.3 MI) designed for the 1.8 MHz S5-1 transducer while waiting for percutaneous coronary intervention. A control group (PCI only) undergoing low MI (\<0.2 MI) imaging only with limited (no more than 3) diagnostic high MI impulses to assess regional wall motion and microvascular perfusion before and after PCI. High MI will continue after PCI procedure until complete a total of 50 minutes.

Procedure: Therapeutic ultrasound with 20 usec

Subproject 6 - Pre-hospital care (ambulance)

Participants with acute STEMI routing from the ambulance to the emergency department will receive intravenous infusion of microbubbles (3% Definity) with therapeutic ultrasound with 4-20 usec and custom designed high mechanical index (MI) impulses (1.1 to 1.3 MI) designed for the 1.8 MHz S5-1 transducer while waiting for percutaneous coronary intervention. A control group (PCI only) undergoing low MI (\<0.2) imaging only with limited (no more than 3) diagnostic high MI impulses to assess regional wall motion and microvascular perfusion before and after PCI. High MI will continue after PCI procedure until complete a total of 50 minutes.

Procedure: Therapeutic ultrasound with 20 usec

Interventions

A custom designed high mechanical index (MI) impulses at 4-20 usec and \>1.0 mechanical index designed for the 1.8 MHz S5-1 transducer

Subproject 1 - acute STEMISubproject 2 - acute STEMI initially treated with fibrinolyticSubproject 3 - NSTEMISubproject 4 - No reflowSubproject 6 - Pre-hospital care (ambulance)

Eligibility Criteria

Age30 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)
Sampling MethodNon-Probability Sample
Study Population

Patients with acute ST elevation myocardial infarction (STEMI) with less than 12 hours of chest pain onset, STEMI initially treated with fibrinonilytic therapy, NSTEMI or high-risk angina undergoing early invasive PCI, anterior wall (LAD territory) acute STEMI, and acute STEMI with less than 12 hours of chest pain onset in the pre-care setting (ambulance) eligible for emergent percutaneous coronary intervention therapy.

You may qualify if:

  • Age ≥30 years with STEMI with less than 12 hours of chest pain onset.
  • Age ≥30 years with STEMI initially treated in a primary setting by fibrinolytic therapy within 12h
  • Age ≥30 years with NSTEMI with high-risk unstable angina who will undergo elective PCI
  • Eligible for emergent PCI therapy.
  • No contraindications or hypersensitivities to ultrasound contrast agents

You may not qualify if:

  • 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.
  • Women of childbearing potential.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (2)

Department of Internal Medicine, Division of Cardiovascular Medicine, University of Nebraska Medical Center

Omaha, Nebraska, 68198, United States

ACTIVE NOT RECRUITING

Heart Institute of Clinical Hospital of Medical School of University of Sao Paulo

São Paulo, 05403900, Brazil

RECRUITING

Biospecimen

Retention: SAMPLES WITHOUT DNA

Blood sample

MeSH Terms

Conditions

Angina, Unstable

Interventions

Ultrasonic Therapy

Condition Hierarchy (Ancestors)

Angina PectorisMyocardial IschemiaHeart DiseasesCardiovascular DiseasesVascular DiseasesChest PainPainNeurologic ManifestationsSigns and SymptomsPathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

DiathermyHyperthermia, InducedTherapeutics

Study Officials

  • Wilson Mathias Jr, MD, PhD

    Heart Institute - University of São Paulo Medical School

    PRINCIPAL INVESTIGATOR
  • Jeane Tsutsui, MD, PhD

    Heart Institute - University of São Paulo Medical School

    PRINCIPAL INVESTIGATOR
  • Thomas R Porter, MD

    University of Nebraska Medical Center, Omaha, NE

    PRINCIPAL INVESTIGATOR

Central Study Contacts

Wilson Mathias Jr, MD, PhD

CONTACT

Jeane M Tsutsui, MD, PhD

CONTACT

Study Design

Study Type
observational
Observational Model
CASE CONTROL
Time Perspective
PROSPECTIVE
Target Duration
6 Months
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Director Echocardiography Laboratory - Heart Institute

Study Record Dates

First Submitted

January 22, 2021

First Posted

February 1, 2021

Study Start

February 17, 2022

Primary Completion

February 1, 2024

Study Completion

February 1, 2026

Last Updated

October 10, 2023

Record last verified: 2023-10

Data Sharing

IPD Sharing
Will not share

The data will be saved into a research encrypted platform available only to study group researchers. Participants will be non-identifiable and results will be blinded to reviewers. The platforms included are RedCap and Castor.

Locations