BENEFIT1: DEF-314 Better Accuracy in Ejection Fraction (EF) Assessment With DEFINITY

• Sponsor: Lantheus Medical Imaging (Industry)
• Overall Status: Completed
• CT.gov ID: NCT03571672
• Collaborator: Syneos Health (Other)
• Enrollment: 153
• Locations: 9
• Arm: 1
• Actual Duration (Months): 10.2
• Patients Per Site: 17
• Patients Per Site Per Month: 1.7

Study Details

Study Description

Brief Summary

This is a Phase 3, prospective, open-label, multicenter study to evaluate Left Ventricular Ejection Fraction (LVEF) measurement accuracy and reproducibility of DEFINITY® contrast-enhanced and unenhanced echocardiography as compared with non-contrast cardiac magnetic resonance imaging (CMR) used as the truth standard.

Condition or Disease	Intervention/Treatment	Phase
Cardiac Disease	Drug: DEFINITY	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 153 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Diagnostic
• Official Title: A Phase III, Open-Label, Multicenter Trial to Evaluate Ejection Fraction, End-Diastolic and End-Systolic Volumes, by Unenhanced and DEFINITY®-Enhanced 2D-Echo and Magnetic Resonance Imaging
• Actual Study Start Date: Oct 24, 2018
• Actual Primary Completion Date: Aug 30, 2019
• Actual Study Completion Date: Aug 30, 2019

Arms and Interventions

Arm	Intervention/Treatment
Experimental: DEFINITY Each patient will undergo an unenhanced ultrasound examination and a DEFINITY contrast-enhanced ultrasound	Drug: DEFINITY; All subjects will receive a single dose of DEFINITY®

Outcome Measures

Primary Outcome Measures

1. Absolute Value of LVEF Percentage Differences From CMR by Blinded Reader [Up to 30 days between day of echocardiograms and CMR imaging]

   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.

Secondary Outcome Measures

1. Secondary Objective 1: Absolute Value of LVEF Percentage Differences From CMR by Blinded Reader for Suboptimal Echocardiograms [Up to 30 days between day of echocardiograms and CMR imaging]

   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.

2. Secondary Objective 2: Absolute Value LVEF Percentage Differences From CMR Between Blinded Readers [Up to 30 days between day of echocardiograms and CMR imaging]

   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

3. Secondary Objective 3: Absolute Value End-Diastolic and Systolic Volume Differences From CMR Between Blinded Readers [Up to 30 days between day of echocardiograms and CMR imaging]

   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.

4. Secondary Objective 4: Absolute Value of LVEF Percentage Differences From CMR Between Blinded Readers for Suboptimal Echocardiograms [Up to 30 days between day of echocardiograms and CMR imaging]

   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.

5. Secondary Objective 5: Absolute Value End-Diastolic and Systolic Volume Differences From CMR Between Blinded Readers for Suboptimal Echocardiograms [Up to 30 days between day of echocardiograms and CMR imaging]

   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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

1. Men and women ≥ 18 years of age in sinus rhythm

2. Able to communicate effectively with trial personnel

3. Has undergone a 2D Echo with or without contrast obtained within 6 months prior to enrollment (Day 0)

4. Has provided signed informed consent after receiving a verbal and written explanation of this clinical trial -

Exclusion Criteria:

1. Female subjects who are pregnant or lactating. All women of child bearing potential [WOCBP] must have a negative urine pregnancy test at screening regardless of contraceptive use history.

2. Women of child-bearing potential are excluded unless they:

3. are post-menopausal defined as amenorrhea ≥ 12 consecutive months, OR

4. have undergone successful surgical sterilization (hysterectomy, bilateral tubal ligation or bilateral oophorectomy), OR

5. have been using an adequate and medically approved method of contraception to avoid pregnancy for at least 1 month prior to DEFINITY® dose administration and be willing to continue using the same method for the duration of the study.

6. Current illness or pathology that would prevent undergoing investigational product administration due to a significant safety risk to the patient.

7. Uncontrolled arterial hypertension (defined as systolic blood pressure ≥ 200 mmHg or diastolic blood pressure ≥ 110 mmHg) or arterial hypotension (defined as systolic blood pressure ≤ 90 mmHg).

8. Unstable cardiovascular status defined as:

9. myocardial infarction or unstable angina pectoris within 6 months prior to enrollment/DEFINITY® dose administration day

10. transient ischemic attack or stroke within 3 months prior to DEFINITY® dose administration

11. symptomatic valvular heart disease or moderate to severe stenotic valvular heart disease

12. clinically significant congenital heart defects

13. current uncontrolled cardiac arrhythmias causing symptoms or hemodynamic compromise

14. acute pulmonary embolus or pulmonary infarction

15. acute myocarditis or pericarditis

16. acute aortic dissection

17. atrial fibrillation

18. any major surgery within 4 weeks prior to screening

19. known contraindications to undergoing CMR or claustrophobia

20. participation in any investigational drug, device, or placebo study within 30 days prior to screening

21. known hypersensitivity to perflutren, or any of the excipients in DEFINITY®

22. prisoners or those who are subject to compulsory detention or involuntary incarceration for treatment of either a psychiatric or physical illness (e.g., infectious disease) -

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Banner University of Arizona Medical Center	Tucson	Arizona	United States	85724
2	University of California-San Diego	San Diego	California	United States	92037
3	Alfieri Cardiology	Wilmington	Delaware	United States	19803
4	Henry Ford Hospital	Detroit	Michigan	United States	48208
5	Weill Cornell Medical Center	New York	New York	United States	10021
6	Duke University	Durham	North Carolina	United States	27710
7	University Hospital/Cleveland Medical Center	Cleveland	Ohio	United States	44106
8	Thomas Jefferson University	Philadelphia	Pennsylvania	United States	19107
9	West Virginia University Medical Center	Morgantown	West Virginia	United States	26505

Sponsors and Collaborators

• Lantheus Medical Imaging
• Syneos Health

Investigators

None specified.

Study Documents (Full-Text)

• Study Protocol - Aug 15, 2018
• Statistical Analysis Plan - Oct 6, 2018

More Information

Publications

None provided.

• Responsible Party: Lantheus Medical Imaging
• ClinicalTrials.gov Identifier: NCT03571672
• Other Study ID Numbers: DEF-314
• First Posted: Jun 27, 2018
• Last Update Posted: Dec 17, 2020
• Last Verified: Oct 1, 2020

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Lantheus Medical Imaging: Left Ventricular Ejection Fraction; DEFINITY; Enhanced Echocardiogram; Cardiac Magnetic Resonance
• Additional relevant MeSH terms: Heart Diseases

Study Results

Participant Flow

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

Baseline Characteristics

Arm/Group Title	Definity
Arm/Group Description	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 Participants	153
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	98 64.1%
>=65 years	55 35.9%
Sex: Female, Male (Count of Participants)
Female	51 33.3%
Male	102 66.7%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	18 11.8%
Not Hispanic or Latino	135 88.2%
Unknown or Not Reported	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	2 1.3%
Asian	3 2%
Native Hawaiian or Other Pacific Islander	4 2.6%
Black or African American	37 24.2%
White	104 68%
More than one race	3 2%
Unknown or Not Reported	0 0%
LVEF Group (Count of Participants)
LVEF <30%	35 22.9%
LVEF 30-40%	40 26.1%
LVEF 41-50%	39 25.5%
LVEF >50%	39 25.5%

Outcome Measures

1. Primary Outcome

Title	Absolute Value of LVEF Percentage Differences From CMR by Blinded Reader
Description	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.
Time Frame	Up to 30 days between day of echocardiograms and CMR imaging

Outcome Measure Data

Analysis Population Description

Modified ITT Population

Arm/Group Title	Blinded Reader 1	Blinded Reader 2	Blinded Reader 3
Arm/Group Description	Independent Blinded Reader 1 of 3	Independent Blinded Reader 2 of 3	Independent Blinded Reader 3 of 3
Measure Participants	145	145	145
Echo Enhanced	6.10 (5.319)	6.38 (5.227)	4.93 (4.288)
Echo Unenhanced	6.18 (5.300)	6.61 (5.256)	5.36 (4.498)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Blinded Reader 1
	Comments
	Type of Statistical Test	Superiority
	Comments	Difference between Echo Enhanced and Echo Unenhanced
Statistical Test of Hypothesis	p-Value	0.868
	Comments
	Method	t-test, 2 sided
	Comments	Paired t-test
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.08
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Standard Deviation; Value: 5.980
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Blinded Reader 2
	Comments
	Type of Statistical Test	Superiority
	Comments	Difference between Echo Enhanced and Echo Unenhanced
Statistical Test of Hypothesis	p-Value	0.606
	Comments
	Method	t-test, 2 sided
	Comments	Paired t-test
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.23
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Standard Deviation; Value: 5.445
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Blinded Reader 3
	Comments
	Type of Statistical Test	Superiority
	Comments	Difference between Echo Enhanced and Echo Unenhanced
Statistical Test of Hypothesis	p-Value	0.224
	Comments
	Method	t-test, 2 sided
	Comments	Paired t-test
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.43
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Standard Deviation; Value: 4.212
	Estimation Comments

2. Secondary Outcome

Title	Secondary Objective 1: Absolute Value of LVEF Percentage Differences From CMR by Blinded Reader for Suboptimal Echocardiograms
Description	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.
Time Frame	Up to 30 days between day of echocardiograms and CMR imaging

Outcome Measure Data

Analysis Population Description

Per-protocol population - Sub-optimal Echocardiograms

Arm/Group Title	Blinded Reader 1	Blinded Reader 2	Blinded Reader 3
Arm/Group Description	Independent Blinded Reader 1 of 3	Independent Blinded Reader 2 of 3	Independent Blinded Reader 3 of 3
Measure Participants	59	59	59
Echo Enhanced	7.48 (6.228)	7.16 (6.337)	5.71 (5.293)
Echo Unenhanced	7.16 (6.184)	7.12 (5.381)	5.89 (4.523)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Blinded Reader 1
	Comments
	Type of Statistical Test	Superiority
	Comments	Difference between Echo Enhanced and Echo Unenhanced
Statistical Test of Hypothesis	p-Value	0.715
	Comments
	Method	t-test, 2 sided
	Comments	Paired t-test
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.32
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Standard Deviation; Value: 6.682
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Blinded Reader 2
	Comments
	Type of Statistical Test	Superiority
	Comments	Difference between Echo Enhanced and Echo Unenhanced
Statistical Test of Hypothesis	p-Value	0.956
	Comments
	Method	t-test, 2 sided
	Comments	Paired t-test
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.05
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Standard Deviation; Value: 6.526
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Blinded Reader 3
	Comments
	Type of Statistical Test	Superiority
	Comments	Difference between Echo Enhanced and Echo Unenhanced
Statistical Test of Hypothesis	p-Value	0.771
	Comments
	Method	t-test, 2 sided
	Comments	Paired t-test
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.17
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Standard Deviation; Value: 4.584
	Estimation Comments

3. Secondary Outcome

Title	Secondary Objective 2: Absolute Value LVEF Percentage Differences From CMR Between Blinded Readers
Description	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
Time Frame	Up to 30 days between day of echocardiograms and CMR imaging

Outcome Measure Data

Analysis Population Description

Per-Protocol Population

Arm/Group Title	Blinded Reader 1	Blinded Reader 2	Blinded Reader 3
Arm/Group Description	Independent Blinded Reader 1 of 3	Independent Blinded Reader 2 of 3	Independent Blinded Reader 3 of 3
Measure Participants	145	145	145
Echo Enhanced	6.10 (5.319)	6.38 (5.227)	4.93 (4.288)
Echo Unenhanced	6.18 (0.164)	6.61 (5.256)	5.36 (4.498)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Blinded Reader 1, Blinded Reader 2
	Comments	Inter-Reader Variability Echo Enhanced
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Intra-class Correlation Coefficient
	Estimated Value	0.959
	Confidence Interval	(2-Sided) 95%; 0.944 to 0.970
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Blinded Reader 1, Blinded Reader 2
	Comments	Inter-Reader Variability Echo Unenhanced
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Intra-class Correlation Coefficient
	Estimated Value	0.950
	Confidence Interval	(2-Sided) 95%; 0.931 to 0.964
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Blinded Reader 1, Blinded Reader 3
	Comments	Inter-Reader Variability Echo Enhanced
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Intra-class Correlation Coefficient
	Estimated Value	0.957
	Confidence Interval	(2-Sided) 95%; 0.941 to 0.969
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Blinded Reader 1, Blinded Reader 3
	Comments	Inter-Reader Variability Echo Unenhanced
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Intra-class Correlation Coefficient
	Estimated Value	0.934
	Confidence Interval	(2-Sided) 95%; 0.909 to 0.952
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Blinded Reader 2, Blinded Reader 3
	Comments	Inter-Reader Variability Echo Enhanced
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Intra-class Correlation Coefficient
	Estimated Value	0.961
	Confidence Interval	(2-Sided) 95%; 0.946 to 0.972
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Blinded Reader 2, Blinded Reader 3
	Comments	Inter-Reader Variability Echo Unenhanced
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Intra-class Correlation Coefficient
	Estimated Value	0.937
	Confidence Interval	(2-Sided) 95%; 0.913 to 0.954
	Parameter Dispersion	Type: Value:
	Estimation Comments

4. Secondary Outcome

Title	Secondary Objective 3: Absolute Value End-Diastolic and Systolic Volume Differences From CMR Between Blinded Readers
Description	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.
Time Frame	Up to 30 days between day of echocardiograms and CMR imaging

Outcome Measure Data

Analysis Population Description

Modified ITT Population

Arm/Group Title	Blinded Reader 1	Blinded Reader 2	Blinded Reader 3
Arm/Group Description	Independent Blinded Reader 1 of 3	Independent Blinded Reader 2 of 3	Independent Blinded Reader 3 of 3
Measure Participants	145	145	145
Echo Enhanced End Diastolic	52.31 (35.726)	46.57 (33.785)	39.37 (26.206)
Echo Unenhanced End Diastolic	58.02 (38.483)	56.65 (37.766)	48.07 (31.620)
Echo Enhanced End Systolic	33.56 (28.641)	29.93 (25.845)	26.01 (20.740)
Echo Unenhanced End Systolic	37.53 (30.016)	33.51 (28.079)	30.72 (23.534)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Blinded Reader 1, Blinded Reader 2
	Comments	Inter-reader Variability End Diastolic Echo Enhanced
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Intra-class Correlation Coefficient
	Estimated Value	0.988
	Confidence Interval	(2-Sided) 95%; 0.984 to 0.992
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Blinded Reader 1, Blinded Reader 2
	Comments	Inter-reader Variability End Diastolic Echo Unenhanced
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Intra-class Correlation Coefficient
	Estimated Value	0.986
	Confidence Interval	(2-Sided) 95%; 0.981 to 0.990
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Blinded Reader 1, Blinded Reader 3
	Comments	Inter-reader Variability End Diastolic Echo Enhanced
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Intra-class Correlation Coefficient
	Estimated Value	0.960
	Confidence Interval	(2-Sided) 95%; 0.945 to 0.971
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Blinded Reader 1, Blinded Reader 3
	Comments	Inter-reader Variability End Diastolic Echo Unenhanced
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Intra-class Correlation Coefficient
	Estimated Value	0.925
	Confidence Interval	(2-Sided) 95%; 0.897 to 0.945
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Blinded Reader 2, Blinded Reader 3
	Comments	Inter-reader Variability End Diastolic Echo Enhanced
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Intra-class Correlation Coefficient
	Estimated Value	0.970
	Confidence Interval	(2-Sided) 95%; 0.958 to 0.978
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Blinded Reader 2, Blinded Reader 3
	Comments	Inter-reader Variability End Diastolic Echo Unenhanced
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Intra-class Correlation Coefficient
	Estimated Value	0.909
	Confidence Interval	(2-Sided) 95%; 0.876 to 0.934
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	Blinded Reader 1, Blinded Reader 2
	Comments	Inter-reader Variability End Systolic Echo Enhanced
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Intra-class Correlation Coefficient
	Estimated Value	0.989
	Confidence Interval	(2-Sided) 95%; 0.984 to 0.992
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 8

Statistical Analysis Overview	Comparison Group Selection	Blinded Reader 1, Blinded Reader 2
	Comments	Inter-reader Variability End Systolic Echo Unenhanced
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Intra-class Correlation Coefficient
	Estimated Value	0.985
	Confidence Interval	(2-Sided) 95%; 0.979 to 0.989
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 9

Statistical Analysis Overview	Comparison Group Selection	Blinded Reader 1, Blinded Reader 3
	Comments	Inter-reader Variability End Systolic Echo Enhanced
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Intra-class Correlation Coefficient
	Estimated Value	0.973
	Confidence Interval	(2-Sided) 95%; 0.962 to 0.980
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 10

Statistical Analysis Overview	Comparison Group Selection	Blinded Reader 1, Blinded Reader 3
	Comments	Inter-reader Variability End Systolic Echo Unenhanced
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Intra-class Correlation Coefficient
	Estimated Value	0.947
	Confidence Interval	(2-Sided) 95%; 0.927 to 0.961
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 11

Statistical Analysis Overview	Comparison Group Selection	Blinded Reader 2, Blinded Reader 3
	Comments	Inter-reader Variability End Systolic Echo Enhanced
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Intra-class Correlation Coefficient
	Estimated Value	0.977
	Confidence Interval	(2-Sided) 95%; 0.969 to 0.984
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 12

Statistical Analysis Overview	Comparison Group Selection	Blinded Reader 2, Blinded Reader 3
	Comments	Inter-reader Variability End Systolic Echo Unenhanced
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Intra-class Correlation Coefficient
	Estimated Value	0.937
	Confidence Interval	(2-Sided) 95%; 0.914 to 0.954
	Parameter Dispersion	Type: Value:
	Estimation Comments

5. Secondary Outcome

Title	Secondary Objective 4: Absolute Value of LVEF Percentage Differences From CMR Between Blinded Readers for Suboptimal Echocardiograms
Description	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.
Time Frame	Up to 30 days between day of echocardiograms and CMR imaging

Outcome Measure Data

Analysis Population Description

Per Protocol Population - Sub-Optimal Echocardiograms

Arm/Group Title	Blinded Reader 1	Blinded Reader 2	Blinded Reader 3
Arm/Group Description	Independent Blinded Reader 1 of 3	Independent Blinded Reader 2 of 3	Independent Blinded Reader 3 of 3
Measure Participants	59	59	59
Echo Enhanced	7.48 (6.228)	7.16 (6.337)	5.71 (5.293)
Echo Unenhanced	7.16 (6.184)	7.12 (5.381)	5.89 (4.523)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Blinded Reader 1, Blinded Reader 2
	Comments	Inter-Reader Variability Echo Enhanced Sub-Optimal Echocardiograms
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Intra-class Correlation Coefficient
	Estimated Value	0.945
	Confidence Interval	(2-Sided) 95%; 0.909 to 0.967
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Blinded Reader 1, Blinded Reader 2
	Comments	Inter-Reader Variability Echo Unenhanced Sub-Optimal Echocardiograms
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Intra-class Correlation Coefficient
	Estimated Value	0.917
	Confidence Interval	(2-Sided) 95%; 0.864 to 0.950
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Blinded Reader 1, Blinded Reader 3
	Comments	Inter-Reader Variability Echo Enhanced Sub-Optimal Echocardiograms
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Intra-class Correlation Coefficient
	Estimated Value	0.939
	Confidence Interval	(2-Sided) 95%; 0.900 to 0.963
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Blinded Reader 1, Blinded Reader 3
	Comments	Inter-Reader Variability Echo Unenhanced Sub-Optimal Echocardiograms
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Intra-class Correlation Coefficient
	Estimated Value	0.894
	Confidence Interval	(2-Sided) 95%; 0.827 to 0.935
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Blinded Reader 2, Blinded Reader 3
	Comments	Inter-Reader Variability Echo Enhanced Sub-Optimal Echocardiograms
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Intra-class Correlation Coefficient
	Estimated Value	0.952
	Confidence Interval	(2-Sided) 95%; 0.920 to 0.971
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Blinded Reader 2, Blinded Reader 3
	Comments	Inter-Reader Variability Echo Unenhanced Sub-Optimal Echocardiograms
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Intra-class Correlation Coefficient
	Estimated Value	0.900
	Confidence Interval	(2-Sided) 95%; 0.838 to 0.939
	Parameter Dispersion	Type: Value:
	Estimation Comments

6. Secondary Outcome

Title	Secondary Objective 5: Absolute Value End-Diastolic and Systolic Volume Differences From CMR Between Blinded Readers for Suboptimal Echocardiograms
Description	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.
Time Frame	Up to 30 days between day of echocardiograms and CMR imaging

Outcome Measure Data

Analysis Population Description

Modified ITT population - Sub Optimal Echocardiograms

Arm/Group Title	Blinded Reader 1	Blinded Reader 2	Blinded Reader 3
Arm/Group Description	Independent Blinded Reader 1 of 3	Independent Blinded Reader 2 of 3	Independent Blinded Reader 3 of 3
Measure Participants	59	59	59
Echo Enhanced End Diastolic	62.34 (40.035)	54.68 (37.571)	45.44 (29.702)
Echo Unenhanced End Diastolic	65.45 (43.227)	63.25 (41.700)	53.77 (34.210)
Echo Enhanced End Systolic	39.52 (29.712)	34.00 (26.955)	30.12 (22.174)
Echo Unenhanced End Systolic	39.45 (33.303)	33.97 (29.233)	32.78 (24.522)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Blinded Reader 1, Blinded Reader 2
	Comments	Inter-reader Variability End Diastolic Echo Enhanced
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Intra-class Correlation Coefficient
	Estimated Value	0.976
	Confidence Interval	(2-Sided) 95%; 0.961 to 0.986
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Blinded Reader 1, Blinded Reader 2
	Comments	Inter-reader Variability End Diastolic Echo Unenhanced
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Intra-class Correlation Coefficient
	Estimated Value	0.984
	Confidence Interval	(2-Sided) 95%; 0.974 to 0.991
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Blinded Reader 1, Blinded Reader 3
	Comments	Inter-reader Variability End Diastolic Echo Enhanced
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Intra-class Correlation Coefficient
	Estimated Value	0.933
	Confidence Interval	(2-Sided) 95%; 0.890 to 0.960
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Blinded Reader 1, Blinded Reader 3
	Comments	Inter-reader Variability End Diastolic Echo Unenhanced
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Intra-class Correlation Coefficient
	Estimated Value	0.857
	Confidence Interval	(2-Sided) 95%; 0.770 to 0.912
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Blinded Reader 2, Blinded Reader 3
	Comments	Inter-reader Variability End Diastolic Echo Enhanced
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Intra-class Correlation Coefficient
	Estimated Value	0.948
	Confidence Interval	(2-Sided) 95%; 0.914 to 0.969
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Blinded Reader 2, Blinded Reader 3
	Comments	Inter-reader Variability End Diastolic Echo Unenhanced
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Intra-class Correlation Coefficient
	Estimated Value	0.824
	Confidence Interval	(2-Sided) 95%; 0.721 to 0.892
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	Blinded Reader 1, Blinded Reader 2
	Comments	Inter-reader Variability End Systolic Echo Enhanced
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Intra-class Correlation Coefficient
	Estimated Value	0.982
	Confidence Interval	(2-Sided) 95%; 0.970 to 0.989
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 8

Statistical Analysis Overview	Comparison Group Selection	Blinded Reader 1, Blinded Reader 2
	Comments	Inter-reader Variability End Systolic Echo Unenhanced
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Intra-class Correlation Coefficient
	Estimated Value	0.974
	Confidence Interval	(2-Sided) 95%; 0.957 to 0.985
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 9

Statistical Analysis Overview	Comparison Group Selection	Blinded Reader 1, Blinded Reader 3
	Comments	Inter-reader Variability End Systolic Echo Enhanced
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Intra-class Correlation Coefficient
	Estimated Value	0.948
	Confidence Interval	(2-Sided) 95%; 0.915 to 0.969
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 10

Statistical Analysis Overview	Comparison Group Selection	Blinded Reader 1, Blinded Reader 3
	Comments	Inter-reader Variability End Systolic Echo Unenhanced
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Intra-class Correlation Coefficient
	Estimated Value	0.890
	Confidence Interval	(2-Sided) 95%; 0.822 to 0.933
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 11

Statistical Analysis Overview	Comparison Group Selection	Blinded Reader 2, Blinded Reader 3
	Comments	Inter-reader Variability End Systolic Echo Enhanced
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Intra-class Correlation Coefficient
	Estimated Value	0.959
	Confidence Interval	(2-Sided) 95%; 0.932 to 0.975
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 12

Statistical Analysis Overview	Comparison Group Selection	Blinded Reader 2, Blinded Reader 3
	Comments	Inter-reader Variability End Systolic Echo Unenhanced
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Intra-class Correlation Coefficient
	Estimated Value	0.872
	Confidence Interval	(2-Sided) 95%; 0.794 to 0.922
	Parameter Dispersion	Type: Value:
	Estimation Comments

Adverse Events

Time Frame	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).
Arm/Group Title	Definity
Arm/Group Description	Each patient will undergo an unenhanced ultrasound examination and a single dose DEFINITY contrast-enhanced ultrasound during the same imaging session
All Cause Mortality
	Definity
	Affected / at Risk (%)	# Events
Total	0/153 (0%)
Serious Adverse Events
	Definity
	Affected / at Risk (%)	# Events
Total	0/153 (0%)
Other (Not Including Serious) Adverse Events
	Definity
	Affected / at Risk (%)	# Events
Total	0/153 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.