Trial Outcomes & Findings for DEF-314 Better Accuracy in Ejection Fraction (EF) Assessment With DEFINITY (NCT NCT03571672)

NCT ID: NCT03571672

Last Updated: 2020-12-17

Results Overview

Demonstrate improvement in accuracy in left ventricular ejection fraction (LVEF) assessment using Definity contrast-enhanced over unenhanced echocardiography by comparing LVEF Percentage Differences from CMR measured by 3 independent blinded image readers.

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 153 participants
• Primary outcome timeframe: Up to 30 days between day of echocardiograms and CMR imaging
• Results posted on: 2020-12-17

Participant Flow

Participant milestones

Measure	Definity Each patient will undergo an unenhanced ultrasound examination and a DEFINITY contrast-enhanced ultrasound DEFINITY: All subjects will receive a single dose of DEFINITY®
Overall Study STARTED	153
Overall Study COMPLETED	148
Overall Study NOT COMPLETED	5

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

DEF-314 Better Accuracy in Ejection Fraction (EF) Assessment With DEFINITY

Baseline characteristics by cohort

Measure	Definity n=153 Participants Each patient will undergo an unenhanced ultrasound examination and a DEFINITY contrast-enhanced ultrasound DEFINITY: All subjects will receive a single dose of DEFINITY®
Age, Categorical <=18 years	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	98 Participants n=5 Participants
Age, Categorical >=65 years	55 Participants n=5 Participants
Sex: Female, Male Female	51 Participants n=5 Participants
Sex: Female, Male Male	102 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	18 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	135 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	2 Participants n=5 Participants
Race (NIH/OMB) Asian	3 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	4 Participants n=5 Participants
Race (NIH/OMB) Black or African American	37 Participants n=5 Participants
Race (NIH/OMB) White	104 Participants n=5 Participants
Race (NIH/OMB) More than one race	3 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants
LVEF Group LVEF <30%	35 Participants n=5 Participants
LVEF Group LVEF 30-40%	40 Participants n=5 Participants
LVEF Group LVEF 41-50%	39 Participants n=5 Participants
LVEF Group LVEF >50%	39 Participants n=5 Participants

PRIMARY outcome

Timeframe: Up to 30 days between day of echocardiograms and CMR imaging

Population: Modified ITT Population

Demonstrate improvement in accuracy in left ventricular ejection fraction (LVEF) assessment using Definity contrast-enhanced over unenhanced echocardiography by comparing LVEF Percentage Differences from CMR measured by 3 independent blinded image readers.

Outcome measures

Measure	Blinded Reader 1 n=145 Participants Independent Blinded Reader 1 of 3	Blinded Reader 2 n=145 Participants Independent Blinded Reader 2 of 3	Blinded Reader 3 n=145 Participants Independent Blinded Reader 3 of 3
Absolute Value of LVEF Percentage Differences From CMR by Blinded Reader Echo Enhanced	6.10 Percent Ejection Fraction Standard Deviation 5.319	6.38 Percent Ejection Fraction Standard Deviation 5.227	4.93 Percent Ejection Fraction Standard Deviation 4.288
Absolute Value of LVEF Percentage Differences From CMR by Blinded Reader Echo Unenhanced	6.18 Percent Ejection Fraction Standard Deviation 5.300	6.61 Percent Ejection Fraction Standard Deviation 5.256	5.36 Percent Ejection Fraction Standard Deviation 4.498

SECONDARY outcome

Timeframe: Up to 30 days between day of echocardiograms and CMR imaging

Population: Per-protocol population - Sub-optimal Echocardiograms

Demonstrate improvement in accuracy in left ventricular ejection fraction (LVEF) assessment using DEFINITY® contrast-enhanced over unenhanced echocardiography in subjects with suboptimal echocardiograms by comparing LVEF percentage differences from CMR measured by 3 independent readers.

Outcome measures

Measure	Blinded Reader 1 n=59 Participants Independent Blinded Reader 1 of 3	Blinded Reader 2 n=59 Participants Independent Blinded Reader 2 of 3	Blinded Reader 3 n=59 Participants Independent Blinded Reader 3 of 3
Secondary Objective 1: Absolute Value of LVEF Percentage Differences From CMR by Blinded Reader for Suboptimal Echocardiograms Echo Enhanced	7.48 Percent Ejection Fraction Standard Deviation 6.228	7.16 Percent Ejection Fraction Standard Deviation 6.337	5.71 Percent Ejection Fraction Standard Deviation 5.293
Secondary Objective 1: Absolute Value of LVEF Percentage Differences From CMR by Blinded Reader for Suboptimal Echocardiograms Echo Unenhanced	7.16 Percent Ejection Fraction Standard Deviation 6.184	7.12 Percent Ejection Fraction Standard Deviation 5.381	5.89 Percent Ejection Fraction Standard Deviation 4.523

SECONDARY outcome

Timeframe: Up to 30 days between day of echocardiograms and CMR imaging

Population: Per-Protocol Population

Demonstrate a reduction in inter-reader variability for the assessment of left ventricular ejection fraction using DEFINITY® contrast-enhanced versus unenhanced echocardiography by comparing LVEF Percentage Differences from CMR between 3 independent blinded readers

Outcome measures

Measure	Blinded Reader 1 n=145 Participants Independent Blinded Reader 1 of 3	Blinded Reader 2 n=145 Participants Independent Blinded Reader 2 of 3	Blinded Reader 3 n=145 Participants Independent Blinded Reader 3 of 3
Secondary Objective 2: Absolute Value LVEF Percentage Differences From CMR Between Blinded Readers Echo Enhanced	6.10 Percent Ejection Fraction Standard Deviation 5.319	6.38 Percent Ejection Fraction Standard Deviation 5.227	4.93 Percent Ejection Fraction Standard Deviation 4.288
Secondary Objective 2: Absolute Value LVEF Percentage Differences From CMR Between Blinded Readers Echo Unenhanced	6.18 Percent Ejection Fraction Standard Deviation 0.164	6.61 Percent Ejection Fraction Standard Deviation 5.256	5.36 Percent Ejection Fraction Standard Deviation 4.498

SECONDARY outcome

Timeframe: Up to 30 days between day of echocardiograms and CMR imaging

Population: Modified ITT Population

Demonstrate a reduction in inter-reader variability for the assessment of end-diastolic and systolic volumes using DEFINITY® contrast-enhanced versus unenhanced echocardiography by comparing end-diastolic and systolic volume differences from CMR between 3 independent blinded readers.

Outcome measures

Measure	Blinded Reader 1 n=145 Participants Independent Blinded Reader 1 of 3	Blinded Reader 2 n=145 Participants Independent Blinded Reader 2 of 3	Blinded Reader 3 n=145 Participants Independent Blinded Reader 3 of 3
Secondary Objective 3: Absolute Value End-Diastolic and Systolic Volume Differences From CMR Between Blinded Readers Echo Enhanced End Diastolic	52.31 mL Standard Deviation 35.726	46.57 mL Standard Deviation 33.785	39.37 mL Standard Deviation 26.206
Secondary Objective 3: Absolute Value End-Diastolic and Systolic Volume Differences From CMR Between Blinded Readers Echo Unenhanced End Diastolic	58.02 mL Standard Deviation 38.483	56.65 mL Standard Deviation 37.766	48.07 mL Standard Deviation 31.620
Secondary Objective 3: Absolute Value End-Diastolic and Systolic Volume Differences From CMR Between Blinded Readers Echo Enhanced End Systolic	33.56 mL Standard Deviation 28.641	29.93 mL Standard Deviation 25.845	26.01 mL Standard Deviation 20.740
Secondary Objective 3: Absolute Value End-Diastolic and Systolic Volume Differences From CMR Between Blinded Readers Echo Unenhanced End Systolic	37.53 mL Standard Deviation 30.016	33.51 mL Standard Deviation 28.079	30.72 mL Standard Deviation 23.534

SECONDARY outcome

Timeframe: Up to 30 days between day of echocardiograms and CMR imaging

Population: Per Protocol Population - Sub-Optimal Echocardiograms

Demonstrate a reduction in inter-reader variability for the assessment of left ventricular ejection fraction using DEFINITY® contrast-enhanced versus unenhanced echocardiography by comparing LVEF Percentage Differences from CMR between 3 independent blinded readers in subjects with suboptimal echocardiograms.

Outcome measures

Measure	Blinded Reader 1 n=59 Participants Independent Blinded Reader 1 of 3	Blinded Reader 2 n=59 Participants Independent Blinded Reader 2 of 3	Blinded Reader 3 n=59 Participants Independent Blinded Reader 3 of 3
Secondary Objective 4: Absolute Value of LVEF Percentage Differences From CMR Between Blinded Readers for Suboptimal Echocardiograms Echo Enhanced	7.48 Percent Ejection Fraction Standard Deviation 6.228	7.16 Percent Ejection Fraction Standard Deviation 6.337	5.71 Percent Ejection Fraction Standard Deviation 5.293
Secondary Objective 4: Absolute Value of LVEF Percentage Differences From CMR Between Blinded Readers for Suboptimal Echocardiograms Echo Unenhanced	7.16 Percent Ejection Fraction Standard Deviation 6.184	7.12 Percent Ejection Fraction Standard Deviation 5.381	5.89 Percent Ejection Fraction Standard Deviation 4.523

SECONDARY outcome

Timeframe: Up to 30 days between day of echocardiograms and CMR imaging

Population: Modified ITT population - Sub Optimal Echocardiograms

Demonstrate a reduction in inter-reader variability for the assessment of end-diastolic/systolic volumes using DEFINITY® contrast-enhanced versus unenhanced echocardiography by comparing end-diastolic and systolic volume differences from CMR between 3 independent blinded readers in subjects with suboptimal echocardiograms.

Outcome measures

Measure	Blinded Reader 1 n=59 Participants Independent Blinded Reader 1 of 3	Blinded Reader 2 n=59 Participants Independent Blinded Reader 2 of 3	Blinded Reader 3 n=59 Participants Independent Blinded Reader 3 of 3
Secondary Objective 5: Absolute Value End-Diastolic and Systolic Volume Differences From CMR Between Blinded Readers for Suboptimal Echocardiograms Echo Enhanced End Diastolic	62.34 mL Standard Deviation 40.035	54.68 mL Standard Deviation 37.571	45.44 mL Standard Deviation 29.702
Secondary Objective 5: Absolute Value End-Diastolic and Systolic Volume Differences From CMR Between Blinded Readers for Suboptimal Echocardiograms Echo Unenhanced End Diastolic	65.45 mL Standard Deviation 43.227	63.25 mL Standard Deviation 41.700	53.77 mL Standard Deviation 34.210
Secondary Objective 5: Absolute Value End-Diastolic and Systolic Volume Differences From CMR Between Blinded Readers for Suboptimal Echocardiograms Echo Enhanced End Systolic	39.52 mL Standard Deviation 29.712	34.00 mL Standard Deviation 26.955	30.12 mL Standard Deviation 22.174
Secondary Objective 5: Absolute Value End-Diastolic and Systolic Volume Differences From CMR Between Blinded Readers for Suboptimal Echocardiograms Echo Unenhanced End Systolic	39.45 mL Standard Deviation 33.303	33.97 mL Standard Deviation 29.233	32.78 mL Standard Deviation 24.522

Adverse Events

Definity

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Adverse event data not reported

Additional Information

Istvan Molnar

Lantheus Medical Imaging, Inc

Phone: 978-671-8686

Email: istvan.molnar@lantheus.com

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place