Evaluation of Safety and Efficacy of Lumason/SonoVue in Subjects Undergoing Pharmacologic Stress BR1-142

A Prospective Multicenter Phase III Clinical Evaluation of the Safety and Efficacy of Lumason™/SonoVue® in Subjects Undergoing Pharmacologic Stress Echocardiography With Dobutamine for the Diagnosis of Coronary Artery Disease

The purpose of this study was to assess the safety and efficacy of Lumason-enhanced dobutamine stress echo (DSE) in subjects having a suboptimal left ventricular endocardial border delineation (LV EBD) at rest and who were scheduled for coronary angiography.

Study Overview

• Status: Completed
• Conditions: Coronary Artery Disease
• Intervention / Treatment: Drug: Lumason

Detailed Description

The study was designed to assess the safety and efficacy of Lumason at improving the visualization of the LV EBD during pharmacologic stress echocardiography examinations and for detection or exclusion of the coronary artery disease (CAD). The study population consisted of adult subjects referred for pharmacological stress echocardiography and with suboptimal image quality during unenhanced ultrasound imaging at rest who had known or suspected CAD. Subjects enrolled in the study represented subjects who could benefit most from CEUS stress echocardiography.

• Study Type: Interventional
• Enrollment (Actual): 174
• Phase: Phase 3

Contacts and Locations

Study Locations

• Belgium
  • Bruxelles, Belgium, 1200
    • Cliniques Universitaires Saint-Luc Unité de Pathologie Cardio-Vasculaire / Cardiologie
  • Edegem, Belgium, 2650
    • Antwerp University Hospital
• Canada
  • Ontario
    • Toronto, Ontario, Canada, M5B 1W8
      • St. Michael's Hospital
• United Kingdom
  • London, United Kingdom, W12 0HS
    • Hammersmith Hospital
  • Middlesex
    • Harrow, Middlesex, United Kingdom, HA1 3UJ
      • Northwick Park Hospital
• United States
  • California
    • Santa Ana, California, United States, 92704
      • Coastal Multi-Specialty Research, Coastal Heart Medical Group
  • Delaware
    • Wilmington, Delaware, United States, 19803
      • Alfieri Cardiology
  • Florida
    • Homestead, Florida, United States, 33030
      • Homestead Cardiac and Vein Center
  • Louisiana
    • New Orleans, Louisiana, United States, 70121
      • Ochsner Clinic Foundation
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • St. Louis University Hospital
  • Nebraska
    • Omaha, Nebraska, United States, 68198
      • University of Nebraska Medical Center
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Duke University Medical Center Cardiac Diagnostic Unit
  • Texas
    • Galveston, Texas, United States, 77555
      • University of Texas Medical Branch at Galveston

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Provided written Informed Consent and comply with protocol requirements;
• Was at least 18 years of age;
• Had suspected of having CAD and undergoing coronary angiography within 6 months after the LUMASON DSE.
• Had undergone a previous echocardiography prior to enrollment; resulting in suboptimal unenhanced images at rest, defined as ≥ 2 suboptimal adjacent segments in any apical view.

Exclusion Criteria:

• Was a pregnant or lactating female. Exclude the possibility of pregnancy: by testing on site at the institution (serum or urine βHCG) within 24 hours prior to the start of LUMASON administration(s), by surgical history (e.g., tubal ligation or hysterectomy), post menopausal with a minimum 1 year without menses;

• Had any known hypersensitivity to 1 or more ingredients of LUMASON (sulfur hexafluoride or to any components of LUMASON);
• Had any known hypersensitivity to dobutamine;
• Had an ongoing or recent (within the last 30 days) acute myocardial infarction;
• Had known right-to-left, bidirectional or transient cardiac shunt (ruled out with agitated saline study performed before administration of LUMASON);
• Had electrolyte (especially potassium and magnesium) abnormalities;
• Had unstable pulmonary and/or systemic hemodynamic conditions e.g.:

decompensated or inadequately controlled congestive heart failure (NYHA Class IV);

• hypovolemia;
• uncontrolled hypertension, i.e. resting systolic blood pressure >200 mmHg or diastolic blood pressure >110 mmHg;
• unstable angina;
• acute coronary syndrome;
• aortic dissection;
• acute pericarditis,
• myocarditis, or endocarditis;
• stenosis of the main left coronary artery;
• hemodynamically significant outflow obstruction of the left ventricle, including hypertrophic obstructive cardiomyopathy;
• hemodynamically significant cardiac valvular defect;
• acute pulmonary embolism;
• Had uncontrolled cardiac arrhythmias;
• Had significant disturbance in conduction;
• Had hypertrophic subaortic stenosis;
• Had an acute illness (e.g., infections, hyperthyroidism, or severe anemia);
• Was previously entered into this study or received an investigational compound within 30 days before admission into this study;
• Had been treated with any other contrast agent either intravascularly or orally within 48 hours of the first LUMASON administration;
• Had any medical condition or other circumstances which would significantly decrease the chances of obtaining reliable data, achieving study objectives, or completing the study and/or postdose follow-up examinations;

In addition, due to the use of Atropine in subjects who had not reached targeted heart rate with peak dobutamine infusion, subjects with the following were excluded:

• Glaucoma;
• Pyloric stenosis;
• Prostatic hypertrophy.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Lumason; Lumason (sulfur hexafluoride lipid-type A microspheres) 2 mL IV injection	Drug: Lumason; Lumason (sulfur hexafluoride-type A microspheres) an ultrasound contrast agent was administered as 2 single 2-mL IV injections during rest and stress echocardiography; Other Names: SonoVue

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Sensitivity and Specificity of Lumason Enhanced Dobutamine Stress Echo (DSE) for Detection or Exclusion of Coronary Artery Disease (CAD)	The diagnostic performance of the echocardiographic images was compared to the truth standard to determine sensitivity and specificity. A diagnosis of CAD was determined for both the echo images and truth standard (positive diagnosis for CAD is defined as >/= 50% stenosis of any vessel on coronary angiography or if no coronary angiography was performed the occurence of a cardiac event based on clinical information for up to 6 months post dose; otherwise the diagnosis was negative). Results for sensitivity and specificity are reflected based on difference between contrast enhanced stress echo and unenhanced stress echo. Results for analysis of data based on majority assessment from the three off-site blinded readers are presented. Sensitivity and specificity are the percentages of correctly diagnosed subjects by stress echo over the total positive and negative subjects according to the truth standard respectively.	Participants were followed until they had coronary angiography or up to 6 months post dose to collect clinical information on cardiac events if no coronary angiography were performed
Reader-Specific Percentages of Participants Identified as Having a Critical Shift From Suboptimal to Optimal Echocardiographic Images	The percentage of subjects with suboptimal images (defined as >= 2 adjacent segments with inadequate LV EBD in any of the 3 apical views) at unenhanced stress echo converted to adequate (reduction of suboptimal segments in any of the 3 apical views) at contrast-enhanced stress echo	Participants were followed until they had coronary angiography or up to 6 months post dose to collect clinical information on cardiac events if no coronary angiography was performed

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Total LV EBD	Measured as the change in the total LV EBD score based on the 17 segments, from peak stress unenhanced vs. peak stress contrast-enhanced. Total LV EBD score ranges from 0 to 34 and higher score is better outcome.	Participants were followed until they had coronary angiography or up to 6 months post dose to collect clinical information on cardiac events if no coronary angiography was performed
Number of Participants With Adverse Events	To obtain safety data in subjects administered Lumason during echocardiography	72 hours post dose

Collaborators and Investigators

• Sponsor: Bracco Diagnostics, Inc

Study record dates

Study Major Dates

• Study Start (Actual): October 12, 2015
• Primary Completion (Actual): June 22, 2017
• Study Completion (Actual): February 25, 2018

Study Registration Dates

• First Submitted: August 11, 2015
• First Submitted That Met QC Criteria: September 15, 2015
• First Posted (Estimate): September 17, 2015

Study Record Updates

• Last Update Posted (Actual): July 7, 2021
• Last Update Submitted That Met QC Criteria: June 14, 2021
• Last Verified: August 1, 2018

More Information

Terms related to this study

• Keywords: coronary artery disease; Lumason; stress echo; Dobutamine stress echo
• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Coronary Artery Disease; Myocardial Ischemia; Coronary Disease
• Other Study ID Numbers: BR1-142

Plan for Individual participant data (IPD)

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