Coronary Artery DiseasePhase 3NCT02522481

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

A Phase 3 study testing Lumason in people with Coronary Artery Disease, run by Bracco Diagnostics, Inc at 17 sites in 4 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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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. Read more about this study

Who is it for?: Ages 18 years and older
Conditions the study is for: Coronary Artery Disease
What is being tested?: Lumason
Type of treatment: Injection or infusion
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 175 participants
Where: 17 sitesin 4 countries
Study dates: 24 Sep 2015to 25 Feb 2018
Phase: Phase 3
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 years and older
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

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.

Who cannot join

Was a pregnant or lactating female. Excluded 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;

Show all 30Show fewer

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.

Trial locations and contacts

17 sites in 4 countries.

Country

City, postcode or hospital

17 sites in 4 countries

United States10 sites

Community Heart and Vascular Community Hospital East
Indianapolis, Indiana, 46250
St. Luke's Mid-America Heart Institute
Kansas City, Missouri, 64111
University of California San Diego
La Jolla, California, 92037
Morristown Medical Center
Morristown, New Jersey, 07960
Mount Sinai Medical Center
New York, New York, 10029
Cardiology Physicians, PA
Newark, Delaware, 19713
North Kansas City Hospital
North Kansas City, Missouri, 64116
The Institute for Clinical Research Holy Name Medical Center
Teaneck, New Jersey, 07666
Sarver Heart Center, University of Arizona
Tucson, Arizona, 85724
Interventional Cardiology Medical Group, Inc.
West Hills, California, 91037

Other trials in United States

Germany4 sites

Medizinische Klinik m.S. Kardiologie und Angiologie, Charité Universitätsmedizin Berlin
Berlin, 10117
Klinikum Lünen, St. Marien-Hospital GmbH
Lünen, 44534
Universitätsmedizin Mainz
Mainz, 55131
Kardiologie Klinik Dr. Müller GmbH, Peter Osypka Heart Center
Munich, 81379

Other trials in Germany

Italy2 sites

Azienda Ospedaliera Universitaria Parma
Parma, 43126
Azienda Policlinico Umberto I Università degli Studi di Roma La Sapienza
Rome, 00161

Other trials in Italy

Canada1 site

Mazankowski Alberta Heart Institute, University of Alberta Hospital
Edmonton, Alberta, T6G2B7

Other trials in Canada

About this study

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

Read the 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 contrast-enhanced ultrasound (CEUS) stress echocardiography.

Conditions: Coronary Artery Disease
Being tested: Lumason
Keywords: Lumason, Dobutamine stress echo, stress echo, coronary artery disease
Medical subject headings: Coronary Artery Disease

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

LumasonDrug
Also called SonoVue
Lumason (sulfur hexafluoride-type A microspheres) an ultrasound contrast agent was administered as 2 single 2-mL IV injections during rest and stress echocardiography

Study groups in NCT02522481
Study group	Role	What they receive
Lumason	Experimental	Lumason (sulfur hexafluoride lipid-type A microspheres) 2 mL IV injection Receives: Drug: Lumason

What is being measured

The primary outcome is the main question the study is designed to answer.

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.
Measured: 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 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
Measured: 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 outcomes (2)

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.
Measured: 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
Measured: up to 72 hours post dose

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

24 Sep 201525 Feb 2018

First posted13 Aug 2015 (estimated)
Study start24 Sep 2015
Primary completion7 Nov 2017
Study completion25 Feb 2018

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Other trials for Coronary Artery DiseaseStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 3
Primary purpose: Diagnosis
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Enrolment: 175 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT02522481
Sponsor's protocol ID: BR1-141
Status last verified: Jun 2021
First submitted: 17 Jul 2015
Last updated: 11 Jun 2021
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No
Individual data sharing: No

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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All Coronary Artery Disease trials

Study at a glance

From the registry record, last updated by the sponsor on 11 Jun 2021. Recruitment status is as the sponsor reported it: confirm with the study team.

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
ClinicalTrials.gov ID: NCT02522481
Acronym / sponsor ID: BR1-141
Conditions: Coronary Artery Disease
Keywords: Lumason, Dobutamine stress echo, stress echo, coronary artery disease
Phase: Phase 3
Study type: Interventional
Recruitment status: Completed
Enrolment: 175 participants (actual)
Lead sponsor: Bracco Diagnostics, IncIndustry (pharma, biotech, devices)
Study start: 24 Sep 2015 (actual)
Primary completion: 7 Nov 2017 (actual)
Study completion: 25 Feb 2018 (actual)
First posted: 13 Aug 2015 (estimated)
Results: Posted 5 Aug 2020

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

Study design

Primary purpose: Diagnosis
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Number of arms: 1

Arm	Type	Receives
Lumason	Experimental	Drug: LumasonLumason (sulfur hexafluoride lipid-type A microspheres) 2 mL IV injection

Who may qualify

Ages: 18 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (4 listed)

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.

Key exclusion criteria (30 listed)

Was a pregnant or lactating female. Excluded 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);

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
LumasonAlso: SonoVueLumason (sulfur hexafluoride-type A microspheres) an ultrasound contrast agent was administered as 2 single 2-mL IV injections during rest and stress echocardiography	Drug	Lumason

Primary outcome

Sensitivity and Specificity for Detection or Exclusion of Coronary Artery Disease (CAD)
Time frame: 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
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.
Reader-Specific Percentages of Participants Identified as Having a Critical Shift From Suboptimal to Optimal Echocardiographic Images
Time frame: 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
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

2 secondary outcomes

Change in Total LV EBD
Time frame: 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
Time frame: up to 72 hours post dose

Results and safety

Results posted to the registry on 5 Aug 2020, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Lumason	175	172

Primary outcome: Sensitivity and Specificity for Detection or Exclusion of Coronary Artery Disease (CAD)

Time frame: 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. Number. Unit: percentage of participants

Measure	CE-DSE - UE-DSE n = 170
Sensitivity	8.0
Specificity	33.7

CE-DSE - UE-DSE: p = 0.0896, McNemar
CE-DSE - UE-DSE: p <0.0001, McNemar

Population analysed: Analysis population for coronary artery disease (CAD) included all subjects who received Lumason, had overall diagnostic conclusion of CAD available at peak stress for both UE-DSE and CE-DSE and had a definite truth standard diagnosis (Positive, Negative) for CAD (coronary angiography or 6 months collection of cardiac events follow-up data).

Primary outcome: Reader-Specific Percentages of Participants Identified as Having a Critical Shift From Suboptimal to Optimal Echocardiographic Images

Time frame: 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 (95% Confidence Interval). Unit: percentage of participants

Measure	Reader 1 n = 167	Reader 2 n = 167	Reader 3 n = 167
Value	84.4 (74.4 to 91.7)	93.7 (87.9 to 97.2)	78.8 (67.0 to 87.9)

Population analysed: The analysis population for EBD included all subjects who received Lumason and had EBD data available at peak stress for both UE-DSE and CE-DSE.

2 secondary outcomes are reported in the full results.

Adverse events

Time frame: All adverse events (AE) that occurred from the time the subject signed the Informed Consent Form (ICF) until 72 hours after the last administration of Lumason or until the subject underwent cardiac intervention, whichever came first, were listed [recorded], [with predose AEs flagged in the subject data listings.]. Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Lumason	3 of 173 (1.7%)	21 of 173 (12.1%)	0 of 173

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 11 Jun 2021.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Individual participant dataSharing planned: No

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Melda Dolan, MD study director

Bracco Diagnostics, Inc

17 sites in 4 countries: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Lumason in people with Coronary Artery Disease, run by Bracco Diagnostics, Inc at 17 sites in 4 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 4 inclusion and 30 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 11 Jun 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 17 sites in United States, Germany, Italy, Canada. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 5 Aug 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Sensitivity and Specificity for Detection or Exclusion of Coronary Artery Disease (CAD) (time frame: 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). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02522481.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 11 Jun 2021.