Trial Outcomes & Findings for Evaluation of Safety and Efficacy of Lumason/SonoVue in Subjects Undergoing Pharmacologic Stress BR1-141 (NCT NCT02522481)

Last Updated: 2021-06-11

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

175 participants

Primary outcome timeframe

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

Results posted on

2021-06-11

Participant Flow

Participant milestones

Participant milestones
Measure	Lumason Lumason (sulfur hexafluoride lipid-type A microspheres) 2 mL IV injection 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
Overall Study STARTED	175
Overall Study COMPLETED	172
Overall Study NOT COMPLETED	3

Reasons for withdrawal

Reasons for withdrawal
Measure	Lumason Lumason (sulfur hexafluoride lipid-type A microspheres) 2 mL IV injection 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
Overall Study discontinued	1
Overall Study Not dosed	2

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Lumason n=173 Participants Lumason (sulfur hexafluoride lipid-type A microspheres) 2 mL IV injection 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
Age, Categorical <=18 years	0 Participants n=39 Participants
Age, Categorical Between 18 and 65 years	76 Participants n=39 Participants
Age, Categorical >=65 years	97 Participants n=39 Participants
Age, Continuous	65.0 years STANDARD_DEVIATION 10.47 • n=39 Participants
Sex: Female, Male Female	52 Participants n=39 Participants
Sex: Female, Male Male	121 Participants n=39 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=39 Participants
Race (NIH/OMB) Asian	5 Participants n=39 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=39 Participants
Race (NIH/OMB) Black or African American	4 Participants n=39 Participants
Race (NIH/OMB) White	160 Participants n=39 Participants
Race (NIH/OMB) More than one race	4 Participants n=39 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=39 Participants
BMI	30.33 kg/m^2 STANDARD_DEVIATION 7.252 • n=39 Participants
Height	169.3 cm STANDARD_DEVIATION 10.49 • n=39 Participants
Weight	86.99 kg STANDARD_DEVIATION 21.781 • n=39 Participants

PRIMARY outcome

Timeframe: 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

Population: 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).

Outcome measures

Outcome measures
Measure	CE-DSE - UE-DSE n=170 Participants Difference between contrast-enhanced dobutamine stress echo (CE-DSE) and unenhanced dobutamine stress echo (UE-DSE) (CE-DSE - UE-DSE)	Reader 2 Reader 2 CE-DSE	Reader 3 Reader 3 CE-DSE
Sensitivity and Specificity for Detection or Exclusion of Coronary Artery Disease (CAD) Sensitivity	8.0 percentage of participants	—	—
Sensitivity and Specificity for Detection or Exclusion of Coronary Artery Disease (CAD) Specificity	33.7 percentage of participants	—	—

PRIMARY outcome

Timeframe: 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

Population: 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.

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

Outcome measures

Outcome measures
Measure	CE-DSE - UE-DSE n=167 Participants Difference between contrast-enhanced dobutamine stress echo (CE-DSE) and unenhanced dobutamine stress echo (UE-DSE) (CE-DSE - UE-DSE)	Reader 2 n=167 Participants Reader 2 CE-DSE	Reader 3 n=167 Participants Reader 3 CE-DSE
Reader-Specific Percentages of Participants Identified as Having a Critical Shift From Suboptimal to Optimal Echocardiographic Images	84.4 percentage of participants Interval 74.4 to 91.7	93.7 percentage of participants Interval 87.9 to 97.2	78.8 percentage of participants Interval 67.0 to 87.9

SECONDARY outcome

Timeframe: 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

Population: 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.

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.

Outcome measures

Outcome measures
Measure	CE-DSE - UE-DSE n=167 Participants Difference between contrast-enhanced dobutamine stress echo (CE-DSE) and unenhanced dobutamine stress echo (UE-DSE) (CE-DSE - UE-DSE)	Reader 2 n=167 Participants Reader 2 CE-DSE	Reader 3 n=167 Participants Reader 3 CE-DSE
Change in Total LV EBD Reader 3	17.8 score on a scale Standard Deviation 7.04	23.6 score on a scale Standard Deviation 7.47	5.8 score on a scale Standard Deviation 9.17
Change in Total LV EBD Reader 1	17.5 score on a scale Standard Deviation 10.83	28.1 score on a scale Standard Deviation 8.32	10.6 score on a scale Standard Deviation 11.98
Change in Total LV EBD Reader 2	13.4 score on a scale Standard Deviation 8.57	30.5 score on a scale Standard Deviation 4.81	17.1 score on a scale Standard Deviation 7.87

SECONDARY outcome

Timeframe: up to 72 hours post dose

Population: Safety analysis population includes all subjects who received Lumason

To obtain safety data in subjects administered Lumason during echocardiography

Outcome measures

Outcome measures
Measure	CE-DSE - UE-DSE n=173 Participants Difference between contrast-enhanced dobutamine stress echo (CE-DSE) and unenhanced dobutamine stress echo (UE-DSE) (CE-DSE - UE-DSE)	Reader 2 Reader 2 CE-DSE	Reader 3 Reader 3 CE-DSE
Number of Participants With Adverse Events Number of subjects with adverse events (AE)	21 participants	—	—
Number of Participants With Adverse Events Number of subjects with AEs by intensity - Mild	15 participants	—	—
Number of Participants With Adverse Events Number of subjects with AEs by intensity -Moderate	5 participants	—	—
Number of Participants With Adverse Events Number of subjects with AEs by intensity - Severe	1 participants	—	—
Number of Participants With Adverse Events Number of subjects with serious AEs	3 participants	—	—

Adverse Events

Lumason

Serious events: 3 serious events

Other events: 21 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Lumason n=173 participants at risk Lumason (sulfur hexafluoride lipid-type A microspheres) 2 mL IV injection 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
Vascular disorders phlebitis	0.58% 1/173 • Number of events 1 • 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.]
Cardiac disorders acute myocardial infarction	0.58% 1/173 • Number of events 1 • 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.]
Respiratory, thoracic and mediastinal disorders chronic obstructive pulmonary disease	0.58% 1/173 • Number of events 1 • 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

Other adverse events
Measure	Lumason n=173 participants at risk Lumason (sulfur hexafluoride lipid-type A microspheres) 2 mL IV injection 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
Cardiac disorders Bifascicular block	0.58% 1/173 • Number of events 1 • 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.]
Cardiac disorders Bradycardia	0.58% 1/173 • Number of events 1 • 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.]
Cardiac disorders Ventricular extrasystoles	0.58% 1/173 • Number of events 1 • 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.]
Cardiac disorders Ventricular tachycardia	0.58% 1/173 • Number of events 1 • 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.]
Gastrointestinal disorders Abdominal pain lower	0.58% 1/173 • Number of events 1 • 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.]
Gastrointestinal disorders Mouth ulceration	0.58% 1/173 • Number of events 1 • 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.]
Gastrointestinal disorders Nausea	0.58% 1/173 • Number of events 1 • 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.]
Gastrointestinal disorders Vomiting	0.58% 1/173 • Number of events 1 • 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.]
General disorders Chest discomfort	0.58% 1/173 • Number of events 1 • 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.]
General disorders Chest pain	0.58% 1/173 • Number of events 1 • 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.]
Infections and infestations Bronchitis	0.58% 1/173 • Number of events 1 • 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.]
Infections and infestations Gastrointestinal infection	1.2% 2/173 • Number of events 2 • 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.]
Infections and infestations Nasopharyngitis	1.2% 2/173 • Number of events 2 • 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.]
Infections and infestations Upper respiratory tract infection	0.58% 1/173 • Number of events 1 • 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.]
Investigations Blood glucose increased	0.58% 1/173 • Number of events 1 • 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.]
Investigations Electrocardiogram change	0.58% 1/173 • Number of events 1 • 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.]
Investigations Haematocrit increased	0.58% 1/173 • Number of events 1 • 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.]
Investigations Troponin increased	0.58% 1/173 • Number of events 1 • 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.]
Musculoskeletal and connective tissue disorders Pain in extremity	0.58% 1/173 • Number of events 1 • 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.]
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	0.58% 1/173 • Number of events 1 • 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.]
Vascular disorders Hypotension	0.58% 1/173 • Number of events 1 • 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.]

Additional Information

Melda S. Dolan, MD, FACC, FASE, Head, Medical Affairs and Cardiac Ultrasound

Bracco Diagnostics Inc.

Phone: 1-609-514-2506

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place