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

Coronary Artery Disease Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02552238
• Other study ID #: BR1-142
• Status: Completed
• Phase: Phase 3
• Start date: October 12, 2015
• Est. completion date: February 25, 2018

Study information

• Verified date: August 2018
• Source: Bracco Diagnostics, Inc
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 174
• Est. completion date: February 25, 2018
• Est. primary completion date: June 22, 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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 ßHCG) 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.

Related Conditions & MeSH terms

• Coronary Artery Disease
• Coronary Disease
• Myocardial Ischemia

Intervention

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

Locations

Country	Name	City	State
Belgium	Cliniques Universitaires Saint-Luc Unité de Pathologie Cardio-Vasculaire / Cardiologie	Bruxelles
Belgium	Antwerp University Hospital	Edegem
Canada	St. Michael's Hospital	Toronto	Ontario
United Kingdom	Northwick Park Hospital	Harrow	Middlesex
United Kingdom	Hammersmith Hospital	London
United States	Duke University Medical Center Cardiac Diagnostic Unit	Durham	North Carolina
United States	University of Texas Medical Branch at Galveston	Galveston	Texas
United States	Homestead Cardiac and Vein Center	Homestead	Florida
United States	Ochsner Clinic Foundation	New Orleans	Louisiana
United States	University of Nebraska Medical Center	Omaha	Nebraska
United States	St. Louis University Hospital	Saint Louis	Missouri
United States	Coastal Multi-Specialty Research, Coastal Heart Medical Group	Santa Ana	California
United States	Alfieri Cardiology	Wilmington	Delaware

Sponsors (1)

Lead Sponsor	Collaborator
Bracco Diagnostics, Inc

Countries where clinical trial is conducted

United States,  Belgium,  Canada,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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	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
Secondary	Number of Participants With Adverse Events	To obtain safety data in subjects administered Lumason during echocardiography	72 hours post dose