Trial Outcomes & Findings for Evaluation of Safety and Efficacy of Lumason/SonoVue in Subjects Undergoing Pharmacologic Stress BR1-142 (NCT NCT02552238)

Last Updated: 2021-07-07

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

174 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

2021-07-07

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	174
Overall Study COMPLETED	170
Overall Study NOT COMPLETED	4

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 Withdrawal by Subject	2
Overall Study Adverse Event	2

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Lumason n=172 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=5 Participants
Age, Categorical Between 18 and 65 years	102 Participants n=5 Participants
Age, Categorical >=65 years	70 Participants n=5 Participants
Age, Continuous	61.9 years STANDARD_DEVIATION 11.02 • n=5 Participants
Sex: Female, Male Female	67 Participants n=5 Participants
Sex: Female, Male Male	105 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants
Race (NIH/OMB) Asian	21 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	24 Participants n=5 Participants
Race (NIH/OMB) White	103 Participants n=5 Participants
Race (NIH/OMB) More than one race	24 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants
Height	169.4 cm STANDARD_DEVIATION 10.58 • n=5 Participants
Weight	86.98 kg STANDARD_DEVIATION 21.631 • n=5 Participants
BMI	30.24 kg/m^2 STANDARD_DEVIATION 6.849 • n=5 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: The analysis population for CAD included all subjects who received Lumason, had an 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=168 Participants Difference between CE-DSE and UE-DSE (CE-DSE - UE-DSE)	Reader 2 Reader 2 CE-DSE	Reader 3 Reader 3 CE-DSE
Sensitivity and Specificity of Lumason Enhanced Dobutamine Stress Echo (DSE) for Detection or Exclusion of Coronary Artery Disease (CAD) Sensitivity	16.0 percentage of participants	—	—
Sensitivity and Specificity of Lumason Enhanced Dobutamine Stress Echo (DSE) for Detection or Exclusion of Coronary Artery Disease (CAD) Specificity	37.9 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 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 CE-DSE and 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	93.2 percentage of participants Interval 86.5 to 97.2	89.8 percentage of participants Interval 77.8 to 96.6	93.5 percentage of participants Interval 87.6 to 97.2

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 CE-DSE and 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 1	16.6 total LV EBD Standard Deviation 7.32	30.7 total LV EBD Standard Deviation 4.30	14.1 total LV EBD Standard Deviation 7.35
Change in Total LV EBD Reader 2	20.5 total LV EBD Standard Deviation 8.36	31.6 total LV EBD Standard Deviation 5.93	11.1 total LV EBD Standard Deviation 8.65
Change in Total LV EBD Reader 3	12.1 total LV EBD Standard Deviation 8.00	29.5 total LV EBD Standard Deviation 7.06	17.3 total LV EBD Standard Deviation 9.20

SECONDARY outcome

Timeframe: 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=172 Participants Difference between CE-DSE and 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 who discontinued due to AE	2 participants	—	—
Number of Participants With Adverse Events Number of subjects with AEs	18 participants	—	—
Number of Participants With Adverse Events Number of subjects with AEs by intensity - Mild	10 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	3 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: 18 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Lumason n=172 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 Myocardial Ischemia	0.58% 1/172 • Number of events 1 • All AEs that occurred from the time the subject signed the ICF until 72 hours after the last administration of Lumason or until the subject underwent cardiac intervention, whichever came first, were [recorded] listed, [with predose AEs flagged in the subject data listings.]
Cardiac disorders Ventricular Fibrillation	0.58% 1/172 • Number of events 1 • All AEs that occurred from the time the subject signed the ICF until 72 hours after the last administration of Lumason or until the subject underwent cardiac intervention, whichever came first, were [recorded] listed, [with predose AEs flagged in the subject data listings.]
Investigations Electrocardiogram ST Segment Elevation	0.58% 1/172 • Number of events 1 • All AEs that occurred from the time the subject signed the ICF until 72 hours after the last administration of Lumason or until the subject underwent cardiac intervention, whichever came first, were [recorded] listed, [with predose AEs flagged in the subject data listings.]

Other adverse events

Other adverse events
Measure	Lumason n=172 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 Atrial fibrillation	0.58% 1/172 • Number of events 1 • All AEs that occurred from the time the subject signed the ICF until 72 hours after the last administration of Lumason or until the subject underwent cardiac intervention, whichever came first, were [recorded] listed, [with predose AEs flagged in the subject data listings.]
Gastrointestinal disorders Nausea	1.2% 2/172 • Number of events 2 • All AEs that occurred from the time the subject signed the ICF until 72 hours after the last administration of Lumason or until the subject underwent cardiac intervention, whichever came first, were [recorded] listed, [with predose AEs flagged in the subject data listings.]
General disorders Chest pain	2.9% 5/172 • Number of events 5 • All AEs that occurred from the time the subject signed the ICF until 72 hours after the last administration of Lumason or until the subject underwent cardiac intervention, whichever came first, were [recorded] listed, [with predose AEs flagged in the subject data listings.]
Infections and infestations Urinary tract infection	0.58% 1/172 • Number of events 1 • All AEs that occurred from the time the subject signed the ICF until 72 hours after the last administration of Lumason or until the subject underwent cardiac intervention, whichever came first, were [recorded] listed, [with predose AEs flagged in the subject data listings.]
Investigations Blood creatinine increased	0.58% 1/172 • Number of events 1 • All AEs that occurred from the time the subject signed the ICF until 72 hours after the last administration of Lumason or until the subject underwent cardiac intervention, whichever came first, were [recorded] listed, [with predose AEs flagged in the subject data listings.]
Investigations Blood glucose increased	0.58% 1/172 • Number of events 1 • All AEs that occurred from the time the subject signed the ICF until 72 hours after the last administration of Lumason or until the subject underwent cardiac intervention, whichever came first, were [recorded] listed, [with predose AEs flagged in the subject data listings.]
Investigations Troponin increased	0.58% 1/172 • Number of events 1 • All AEs that occurred from the time the subject signed the ICF until 72 hours after the last administration of Lumason or until the subject underwent cardiac intervention, whichever came first, were [recorded] listed, [with predose AEs flagged in the subject data listings.]
Nervous system disorders Dysgeusia	0.58% 1/172 • Number of events 1 • All AEs that occurred from the time the subject signed the ICF until 72 hours after the last administration of Lumason or until the subject underwent cardiac intervention, whichever came first, were [recorded] listed, [with predose AEs flagged in the subject data listings.]
Nervous system disorders Headache	1.2% 2/172 • Number of events 2 • All AEs that occurred from the time the subject signed the ICF until 72 hours after the last administration of Lumason or until the subject underwent cardiac intervention, whichever came first, were [recorded] listed, [with predose AEs flagged in the subject data listings.]
Nervous system disorders Hypoesthesia	1.2% 2/172 • Number of events 2 • All AEs that occurred from the time the subject signed the ICF until 72 hours after the last administration of Lumason or until the subject underwent cardiac intervention, whichever came first, were [recorded] listed, [with predose AEs flagged in the subject data listings.]
Psychiatric disorders Panic attack	0.58% 1/172 • Number of events 1 • All AEs that occurred from the time the subject signed the ICF until 72 hours after the last administration of Lumason or until the subject underwent cardiac intervention, whichever came first, were [recorded] listed, [with predose AEs flagged in the subject data listings.]
Respiratory, thoracic and mediastinal disorders Dyspnea	0.58% 1/172 • Number of events 1 • All AEs that occurred from the time the subject signed the ICF until 72 hours after the last administration of Lumason or until the subject underwent cardiac intervention, whichever came first, were [recorded] listed, [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