Evaluation of Safety and Efficacy of Lumason/SonoVue in Subjects Undergoing Pharmacologic Stress BR1-141

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: NCT02522481
• Other study ID #: BR1-141
• Status: Completed
• Phase: Phase 3
• Start date: September 24, 2015
• Est. completion date: February 25, 2018

Study information

• Verified date: June 2021
• 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 (CE-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 contrast-enhanced ultrasound (CEUS) stress echocardiography.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 175
• Est. completion date: February 25, 2018
• Est. primary completion date: November 7, 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Provided written Informed Consent and was willing to comply with protocol requirements;
• Was at least 18 years of age;
• Had suspected or known CAD and was scheduled to undergo 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. Excluded 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
Canada	Mazankowski Alberta Heart Institute, University of Alberta Hospital	Edmonton	Alberta
Germany	Medizinische Klinik m.S. Kardiologie und Angiologie, Charité Universitätsmedizin Berlin	Berlin
Germany	Klinikum Lünen, St. Marien-Hospital GmbH	Lünen
Germany	Universitätsmedizin Mainz	Mainz
Germany	Kardiologie Klinik Dr. Müller GmbH, Peter Osypka Heart Center	Munich
Italy	Azienda Ospedaliera Universitaria Parma	Parma
Italy	Azienda Policlinico Umberto I Università degli Studi di Roma La Sapienza	Rome
United States	Community Heart and Vascular Community Hospital East	Indianapolis	Indiana
United States	St. Luke's Mid-America Heart Institute	Kansas City	Missouri
United States	University of California San Diego	La Jolla	California
United States	Morristown Medical Center	Morristown	New Jersey
United States	Mount Sinai Medical Center	New York	New York
United States	Cardiology Physicians, PA	Newark	Delaware
United States	North Kansas City Hospital	North Kansas City	Missouri
United States	The Institute for Clinical Research Holy Name Medical Center	Teaneck	New Jersey
United States	Sarver Heart Center, University of Arizona	Tucson	Arizona
United States	Interventional Cardiology Medical Group, Inc.	West Hills	California

Sponsors (1)

Lead Sponsor	Collaborator
Bracco Diagnostics, Inc

Countries where clinical trial is conducted

United States,  Canada,  Germany,  Italy, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Sensitivity and Specificity 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 coronary artery disease (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 is performed the occurence of a cardiac event based on clinical information for up to 6 months post dose; otherwise the diagnosis is 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 left ventricular endocardial border delineation (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	up to 72 hours post dose