Trial Outcomes & Findings for DEF-315 Better Accuracy in Ejection Fraction (EF) Assessment With DEFINITY (NCT NCT03719612)

NCT ID: NCT03719612

Last Updated: 2021-01-28

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

160 participants

Primary outcome timeframe

Up to 30 days between day of echocardiograms and CMR imaging

Results posted on

2021-01-28

Participant Flow

Participant milestones

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	160
Overall Study COMPLETED	148
Overall Study NOT COMPLETED	12

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

DEF-315 Better Accuracy in Ejection Fraction (EF) Assessment With DEFINITY

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	DEFINITY® n=160 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	106 Participants n=5 Participants
Age, Categorical >=65 years	54 Participants n=5 Participants
Sex: Female, Male Female	55 Participants n=5 Participants
Sex: Female, Male Male	105 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	14 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	146 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	1 Participants n=5 Participants
Race (NIH/OMB) Asian	3 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	2 Participants n=5 Participants
Race (NIH/OMB) Black or African American	32 Participants n=5 Participants
Race (NIH/OMB) White	120 Participants n=5 Participants
Race (NIH/OMB) More than one race	2 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants
LVEF Group LVEF <30%	45 Participants n=5 Participants
LVEF Group LVEF 30-40%	48 Participants n=5 Participants
LVEF Group LVEF 41-50%	27 Participants n=5 Participants
LVEF Group LVEF >50%	40 Participants n=5 Participants

PRIMARY outcome

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

Population: Modified ITT Population

Outcome measures

Outcome measures
Measure	Blinded Reader 1 n=144 Participants Independent Blinded Reader 1 of 3	Blinded Reader 2 n=144 Participants Independent Blinded Reader 2 of 3	Blinded Reader 3 n=144 Participants Independent Blinded Reader 3 of 3
Absolute Value of LVEF Percentage Differences From CMR by Blinded Reader Echo Enhanced	5.70 Percent Ejection Fraction Standard Deviation 4.292	5.88 Percent Ejection Fraction Standard Deviation 4.330	5.03 Percent Ejection Fraction Standard Deviation 3.548
Absolute Value of LVEF Percentage Differences From CMR by Blinded Reader Echo Unenhanced	6.08 Percent Ejection Fraction Standard Deviation 4.530	6.00 Percent Ejection Fraction Standard Deviation 4.813	5.36 Percent Ejection Fraction Standard Deviation 3.889

SECONDARY outcome

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

Population: Modified ITT 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 blinded readers.

Outcome measures

Outcome measures
Measure	Blinded Reader 1 n=48 Participants Independent Blinded Reader 1 of 3	Blinded Reader 2 n=48 Participants Independent Blinded Reader 2 of 3	Blinded Reader 3 n=48 Participants Independent Blinded Reader 3 of 3
Secondary Objective 1: Absolute Value of LVEF Percentage Differences From CMR by Blinded Reader for Sub-optimal Echocardiograms Echo Enhanced	5.67 Percent Ejection Fraction Standard Deviation 3.717	6.16 Percent Ejection Fraction Standard Deviation 3.746	4.68 Percent Ejection Fraction Standard Deviation 3.456
Secondary Objective 1: Absolute Value of LVEF Percentage Differences From CMR by Blinded Reader for Sub-optimal Echocardiograms Echo Unenhanced	6.95 Percent Ejection Fraction Standard Deviation 5.219	6.81 Percent Ejection Fraction Standard Deviation 4.694	5.33 Percent Ejection Fraction Standard Deviation 3.764

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 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

Outcome measures
Measure	Blinded Reader 1 n=144 Participants Independent Blinded Reader 1 of 3	Blinded Reader 2 n=144 Participants Independent Blinded Reader 2 of 3	Blinded Reader 3 n=144 Participants Independent Blinded Reader 3 of 3
Secondary Objective 2: Absolute Value LVEF Percentage Differences From CMR Between Blinded Readers Echo Enhanced	5.70 Percent Ejection Fraction Standard Deviation 4.292	5.88 Percent Ejection Fraction Standard Deviation 4.330	5.03 Percent Ejection Fraction Standard Deviation 3.548
Secondary Objective 2: Absolute Value LVEF Percentage Differences From CMR Between Blinded Readers Echo Unenhanced	6.08 Percent Ejection Fraction Standard Deviation 4.530	6.00 Percent Ejection Fraction Standard Deviation 4.813	5.36 Percent Ejection Fraction Standard Deviation 3.889

SECONDARY outcome

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

Population: Modified ITT Population

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.

Outcome measures

Outcome measures
Measure	Blinded Reader 1 n=144 Participants Independent Blinded Reader 1 of 3	Blinded Reader 2 n=144 Participants Independent Blinded Reader 2 of 3	Blinded Reader 3 n=144 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 Systolic	38.05 mL Standard Deviation 32.921	32.41 mL Standard Deviation 32.896	31.68 mL Standard Deviation 30.603
Secondary Objective 3: Absolute Value End-diastolic and Systolic Volume Differences From CMR Between Blinded Readers Echo Enhanced End Diastolic	57.85 mL Standard Deviation 44.204	51.13 mL Standard Deviation 43.391	47.97 mL Standard Deviation 40.589
Secondary Objective 3: Absolute Value End-diastolic and Systolic Volume Differences From CMR Between Blinded Readers Echo Unenhanced End Diastolic	64.91 mL Standard Deviation 44.084	62.01 mL Standard Deviation 43.392	48.32 mL Standard Deviation 39.895
Secondary Objective 3: Absolute Value End-diastolic and Systolic Volume Differences From CMR Between Blinded Readers Echo Unenhanced End Systolic	42.87 mL Standard Deviation 34.793	39.08 mL Standard Deviation 34.139	32.45 mL Standard Deviation 31.314

SECONDARY outcome

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

Population: Modified ITT Population - Sub-optimal Echocardiograms

Outcome measures

Outcome measures
Measure	Blinded Reader 1 n=48 Participants Independent Blinded Reader 1 of 3	Blinded Reader 2 n=48 Participants Independent Blinded Reader 2 of 3	Blinded Reader 3 n=48 Participants Independent Blinded Reader 3 of 3
Secondary Objective 4: Absolute Value of LVEF Percentage Differences From CMR Between Readers for Sub-optimal Echocardiograms Echo Enhanced	5.67 Percent Ejection Fraction Standard Deviation 3.717	6.16 Percent Ejection Fraction Standard Deviation 3.746	4.68 Percent Ejection Fraction Standard Deviation 3.456
Secondary Objective 4: Absolute Value of LVEF Percentage Differences From CMR Between Readers for Sub-optimal Echocardiograms Echo Unenhanced	6.95 Percent Ejection Fraction Standard Deviation 5.219	6.81 Percent Ejection Fraction Standard Deviation 4.694	5.33 Percent Ejection Fraction Standard Deviation 3.764

SECONDARY outcome

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

Population: Modified ITT Population - Sub-optimal Echocardiograms

Outcome measures

Outcome measures
Measure	Blinded Reader 1 n=48 Participants Independent Blinded Reader 1 of 3	Blinded Reader 2 n=48 Participants Independent Blinded Reader 2 of 3	Blinded Reader 3 n=48 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	71.67 mL Standard Deviation 49.916	63.73 mL Standard Deviation 49.571	61.86 mL Standard Deviation 47.523
Secondary Objective 5: Absolute Value End-diastolic and Systolic Volume Differences From CMR Between Blinded Readers for Suboptimal Echocardiograms Echo Unenhanced End Diastolic	74.89 mL Standard Deviation 51.468	69.07 mL Standard Deviation 46.316	64.38 mL Standard Deviation 46.827
Secondary Objective 5: Absolute Value End-diastolic and Systolic Volume Differences From CMR Between Blinded Readers for Suboptimal Echocardiograms Echo Enhanced End Systolic	45.59 mL Standard Deviation 32.844	38.55 mL Standard Deviation 33.493	39.52 mL Standard Deviation 30.946
Secondary Objective 5: Absolute Value End-diastolic and Systolic Volume Differences From CMR Between Blinded Readers for Suboptimal Echocardiograms Echo Unenhanced End Systolic	48.00 mL Standard Deviation 37.639	41.88 mL Standard Deviation 32.989	40.72 mL Standard Deviation 32.333

Adverse Events

DEFINITY®

Serious events: 1 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	DEFINITY® n=160 participants at risk Each patient will undergo an unenhanced ultrasound examination and a DEFINITY® contrast-enhanced ultrasound DEFINITY®: All subjects will receive a single dose of DEFINITY®
Gastrointestinal disorders Small intestinal obstruction	0.62% 1/160 • Number of events 1 • Up to 12 days: Enrolled subjects were followed for adverse events and serious adverse events from the time the Informed Consent was signed at screening (Day -7 to Day 0) through 72+/-24 hours after completion of Definity administration (Day 0).

Other adverse events

Adverse event data not reported

Additional Information

Istvan Molnar

Lantheus Medical Imaging, Inc

Phone: 978-671-8686

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place