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CompletedNCT03719612BENEFIT2Updated Jan 28, 2021Results posted

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

A Phase 3 interventional study of DEFINITY® in Cardiac Disease, sponsored by Lantheus Medical Imaging. Completed at 15 sites in United States. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2021-01-28.

Sponsored by Lantheus Medical Imaging · Phase 3, Interventional, and Diagnostic

Phase
Phase 3
Study type
Interventional
Enrollment
160
Allocation
Not applicable
Ages
18 Years and older
Sex
All
01

Study 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.

02

Conditions studied

  • Cardiac Disease

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Keywords

  • Left Ventricular Ejection Fraction
  • DEFINITY®
  • Enhanced Echocardiogram
  • Cardiac Magnetic Resonance
03

In context

Heart Diseases

3,639 studies on the registry are indexed under Heart Diseases; 461 are open to participants now.

This study's enrollment of 160 is above the median of 100 across 1,778 interventional studies indexed under Heart Diseases.

Browse Heart Diseases studies →

Lead sponsor

Lantheus Medical Imaging is the lead sponsor of 30 studies on the registry; 3 are open to participants now.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
18 Years and older
Sexes eligible
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. LVEF measurements obtained via 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

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:

    1. are post-menopausal defined as amenorrhea ≥ 12 consecutive months, OR
    2. have undergone successful surgical sterilization (hysterectomy, bilateral tubal ligation or bilateral oophorectomy), OR
    3. 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.
  3. Current illness or pathology that would prevent undergoing investigational product administration due to a significant safety risk to the patient.
  4. 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).

  5. Unstable cardiovascular status defined as:

    1. myocardial infarction or unstable angina pectoris within 6 months prior to enrollment/DEFINITY® dose administration day
    2. transient ischemic attack or stroke within 3 months prior to DEFINITY® dose administration
    3. symptomatic valvular heart disease or moderate to severe stenotic valvular heart disease
    4. clinically significant congenital heart defects
    5. current uncontrolled cardiac arrhythmias causing symptoms or hemodynamic compromise
    6. acute pulmonary embolus or pulmonary infarction
    7. acute myocarditis or pericarditis
    8. acute aortic dissection
    9. atrial fibrillation
  6. any major surgery within 4 weeks prior to screening
  7. known contraindications to undergoing CMR (e.g. implanted pacemakers, cardioverter, defibrillators) or claustrophobia
  8. participation in any investigational drug, device, or placebo study within 30 days prior to screening
  9. known hypersensitivity to perflutren, or any of the excipients in DEFINITY®
  10. 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).
05

Study design

Phase
Phase 3
Primary purpose
Diagnostic
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrollment
160 participants (actual)

Study arms

  • Experimental
    DEFINITY®

    Each patient will undergo an unenhanced ultrasound examination and a DEFINITY® contrast-enhanced ultrasound

    Drug: DEFINITY®

Interventions

  • DrugDEFINITY®

    All subjects will receive a single dose of DEFINITY®

06

What researchers measure

Primary outcomes

  1. Absolute Value of LVEF Percentage Differences From CMR by Blinded Reader

    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

Secondary outcomes

  1. Secondary Objective 1: Absolute Value of LVEF Percentage Differences From CMR by Blinded Reader for 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.

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

  2. Secondary Objective 2: Absolute Value LVEF Percentage Differences From CMR Between Blinded Readers

    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

  3. Secondary Objective 3: Absolute Value End-diastolic and Systolic Volume Differences From CMR Between Blinded Readers

    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.

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

  4. Secondary Objective 4: Absolute Value of LVEF Percentage Differences From CMR Between Readers for 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.

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

  5. Secondary Objective 5: Absolute Value End-diastolic and Systolic Volume Differences From CMR Between Blinded Readers for Suboptimal 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.

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

07

Results

Posted Jan 7, 2021

Participant flow

Participant flow — Overall Study
MilestoneDEFINITY®
Started160
Completed148
Not completed12

Outcome measures

PrimaryAbsolute Value of LVEF Percentage Differences From CMR by Blinded Reader

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
Reported as:
Mean · Percent Ejection Fraction
Absolute Value of LVEF Percentage Differences From CMR by Blinded Reader
Percent Ejection FractionBlinded Reader 1Blinded Reader 2Blinded Reader 3
Echo Enhanced5.70 ± 4.2925.88 ± 4.3305.03 ± 3.548
Echo Unenhanced6.08 ± 4.5306.00 ± 4.8135.36 ± 3.889
Statistical analysis
  • Blinded Reader 1 · t-test, 2 sided · p = 0.358 · Mean difference (final values): -0.38Paired t-test
  • Blinded Reader 2 · t-test, 2 sided · p = 0.804 · Mean difference (final values): -0.12Paired t-test
  • Blinded Reader 3 · t-test, 2 sided · p = 0.371 · Mean difference (final values): -0.33Paired t-test
SecondarySecondary Objective 1: Absolute Value of LVEF Percentage Differences From CMR by Blinded Reader for 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.

Time frame:
Up to 30 days between day of echocardiogram and CMR imaging
Reported as:
Mean · Percent Ejection Fraction
Secondary Objective 1: Absolute Value of LVEF Percentage Differences From CMR by Blinded Reader for Sub-optimal Echocardiograms
Percent Ejection FractionBlinded Reader 1Blinded Reader 2Blinded Reader 3
Echo Enhanced5.67 ± 3.7176.16 ± 3.7464.68 ± 3.456
Echo Unenhanced6.95 ± 5.2196.81 ± 4.6945.33 ± 3.764
Statistical analysis
  • Blinded Reader 1 · t-test, 2 sided · p = 0.030 · Mean difference (final values): -1.28Paired t-test
  • Blinded Reader 2 · t-test, 2 sided · p = 0.312 · Mean difference (final values): -0.66Paired t-test
  • Blinded Reader 3 · t-test, 2 sided · p = 0.347 · Mean difference (final values): -0.65Paired t-test
SecondarySecondary Objective 2: Absolute Value LVEF Percentage Differences From CMR Between Blinded Readers

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
Reported as:
Mean · Percent Ejection Fraction
Secondary Objective 2: Absolute Value LVEF Percentage Differences From CMR Between Blinded Readers
Percent Ejection FractionBlinded Reader 1Blinded Reader 2Blinded Reader 3
Echo Enhanced5.70 ± 4.2925.88 ± 4.3305.03 ± 3.548
Echo Unenhanced6.08 ± 4.5306.00 ± 4.8135.36 ± 3.889
Statistical analysis
  • Blinded Reader 1 vs Blinded Reader 2 · Intra-class correlation coefficient: 0.984 · 95% CI 0.977 to 0.988
  • Blinded Reader 1 vs Blinded Reader 2 · Intra-class correlation coefficient: 0.953 · 95% CI 0.936 to 0.966
  • Blinded Reader 1 vs Blinded Reader 3 · Intra-class correlation coefficient: 0.970 · 95% CI 0.958 to 0.978
  • Blinded Reader 1 vs Blinded Reader 3 · Intra-class correlation coefficient: 0.944 · 95% CI 0.923 to 0.959
  • Blinded Reader 2 vs Blinded Reader 3 · Intra-class correlation coefficient: 0.961 · 95% CI 0.947 to 0.972
  • Blinded Reader 2 vs Blinded Reader 3 · Intra-class correlation coefficient: 0.942 · 95% CI 0.920 to 0.958
SecondarySecondary Objective 3: Absolute Value End-diastolic and Systolic Volume Differences From CMR Between Blinded Readers

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.

Time frame:
Up to 30 days between day of echocardiogram and CMR imaging
Reported as:
Mean · mL
Secondary Objective 3: Absolute Value End-diastolic and Systolic Volume Differences From CMR Between Blinded Readers
mLBlinded Reader 1Blinded Reader 2Blinded Reader 3
Echo Enhanced End Diastolic57.85 ± 44.20451.13 ± 43.39147.97 ± 40.589
Echo Unenhanced End Diastolic64.91 ± 44.08462.01 ± 43.39248.32 ± 39.895
Echo Enhanced End Systolic38.05 ± 32.92132.41 ± 32.89631.68 ± 30.603
Echo Unenhanced End Systolic42.87 ± 34.79339.08 ± 34.13932.45 ± 31.314
Statistical analysis
  • Blinded Reader 1 vs Blinded Reader 2 · Intra-class correlation coefficient: 0.984 · 95% CI 0.978 to 0.988
  • Blinded Reader 1 vs Blinded Reader 2 · Intra-class correlation coefficient: 0.976 · 95% CI 0.967 to 0.983
  • Blinded Reader 1 vs Blinded Reader 3 · Intra-class correlation coefficient: 0.973 · 95% CI 0.963 to 0.981
  • Blinded Reader 1 vs Blinded Reader 3 · Intra-class correlation coefficient: 0.935 · 95% CI 0.910 to 0.952
  • Blinded Reader 2 vs Blinded Reader 3 · Intra-class correlation coefficient: 0.973 · 95% CI 0.962 to 0.980
  • Blinded Reader 2 vs Blinded Reader 3 · Intra-class correlation coefficient: 0.924 · 95% CI 0.896 to 0.945
  • Blinded Reader 1 vs Blinded Reader 2 · Intra-class correlation coefficient: 0.989 · 95% CI 0.984 to 0.992
  • Blinded Reader 1 vs Blinded Reader 2 · Intra-class correlation coefficient: 0.983 · 95% CI 0.977 to 0.988
  • Blinded Reader 1 vs Blinded Reader 3 · Intra-class correlation coefficient: 0.984 · 95% CI 0.978 to 0.989
  • Blinded Reader 1 vs Blinded Reader 3 · Intra-class correlation coefficient: 0.948 · 95% CI 0.928 to 0.962
  • Blinded Reader 2 vs Blinded Reader 3 · Intra-class correlation coefficient: 0.978 · 95% CI 0.969 to 0.984
  • Blinded Reader 2 vs Blinded Reader 3 · Intra-class correlation coefficient: 0.942 · 95% CI 0.920 to 0.958
SecondarySecondary Objective 4: Absolute Value of LVEF Percentage Differences From CMR Between Readers for 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.

Time frame:
Up to 30 days between day of echocardiograms and CMR imaging
Reported as:
Mean · Percent Ejection Fraction
Secondary Objective 4: Absolute Value of LVEF Percentage Differences From CMR Between Readers for Sub-optimal Echocardiograms
Percent Ejection FractionBlinded Reader 1Blinded Reader 2Blinded Reader 3
Echo Enhanced5.67 ± 3.7176.16 ± 3.7464.68 ± 3.456
Echo Unenhanced6.95 ± 5.2196.81 ± 4.6945.33 ± 3.764
Statistical analysis
  • Blinded Reader 1 vs Blinded Reader 2 · Intra-class correlation coefficient: 0.975 · 95% CI 0.956 to 0.986
  • Blinded Reader 1 vs Blinded Reader 2 · Intra-class correlation coefficient: 0.936 · 95% CI 0.888 to 0.963
  • Blinded Reader 1 vs Blinded Reader 3 · Intra-class correlation coefficient: 0.961 · 95% CI 0.931 to 0.978
  • Blinded Reader 1 vs Blinded Reader 3 · Intra-class correlation coefficient: 0.921 · 95% CI 0.864 to 0.955
  • Blinded Reader 2 vs Blinded Reader 3 · Intra-class correlation coefficient: 0.947 · 95% CI 0.907 to 0.970
  • Blinded Reader 2 vs Blinded Reader 3 · Intra-class correlation coefficient: 0.903 · 95% CI 0.834 to 0.945
SecondarySecondary Objective 5: Absolute Value End-diastolic and Systolic Volume Differences From CMR Between Blinded Readers for Suboptimal 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.

Time frame:
Up to 30 days between day of echocardiograms and CMR imaging
Reported as:
Mean · mL
Secondary Objective 5: Absolute Value End-diastolic and Systolic Volume Differences From CMR Between Blinded Readers for Suboptimal Echocardiograms
mLBlinded Reader 1Blinded Reader 2Blinded Reader 3
Echo Enhanced End Diastolic71.67 ± 49.91663.73 ± 49.57161.86 ± 47.523
Echo Unenhanced End Diastolic74.89 ± 51.46869.07 ± 46.31664.38 ± 46.827
Echo Enhanced End Systolic45.59 ± 32.84438.55 ± 33.49339.52 ± 30.946
Echo Unenhanced End Systolic48.00 ± 37.63941.88 ± 32.98940.72 ± 32.333
Statistical analysis
  • Blinded Reader 1 vs Blinded Reader 2 · Intra-class correlation coefficient: 0.984 · 95% CI 0.971 to 0.991
  • Blinded Reader 1 vs Blinded Reader 2 · Intra-class correlation coefficient: 0.975 · 95% CI 0.956 to 0.986
  • Blinded Reader 1 vs Blinded Reader 3 · Intra-class correlation coefficient: 0.977 · 95% CI 0.959 to 0.987
  • Blinded Reader 1 vs Blinded Reader 3 · Intra-class correlation coefficient: 0.940 · 95% CI 0.896 to 0.966
  • Blinded Reader 2 vs Blinded Reader 3 · Intra-class correlation coefficient: 0.977 · 95% CI 0.959 to 0.987
  • Blinded Reader 2 vs Blinded Reader 3 · Intra-class correlation coefficient: 0.923 · 95% CI 0.866 to 0.956
  • Blinded Reader 1 vs Blinded Reader 2 · Intra-class correlation coefficient: 0.990 · 95% CI 0.982 to 0.994
  • Blinded Reader 1 vs Blinded Reader 2 · Intra-class correlation coefficient: 0.976 · 95% CI 0.957 to 0.986
  • Blinded Reader 1 vs Blinded Reader 3 · Intra-class correlation coefficient: 0.985 · 95% CI 0.973 to 0.991
  • Blinded Reader 1 vs Blinded Reader 3 · Intra-class correlation coefficient: 0.929 · 95% CI 0.876 to 0.959
  • Blinded Reader 2 vs Blinded Reader 3 · Intra-class correlation coefficient: 0.981 · 95% CI 0.966 to 0.989
  • Blinded Reader 2 vs Blinded Reader 3 · Intra-class correlation coefficient: 0.916 · 95% CI 0.855 to 0.952

Adverse events

Collected over 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).. Non-serious events are listed at a 5% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
DEFINITY®0/160 (0%)1/160 (0.6%)0/160 (0%)
Most frequent serious events
Most frequent serious events
EventDEFINITY®
Small intestinal obstructionGastrointestinal disorders1/160

Baseline characteristics

Baseline data are calculated based on Safety Population

Age, Categorical
Age, Categorical(Participants)DEFINITY®
<=18 years0
Between 18 and 65 years106
>=65 years54
Sex: Female, Male
Sex: Female, Male(Participants)DEFINITY®
Female55
Male105
Ethnicity (NIH/OMB)
Ethnicity (NIH/OMB)(Participants)DEFINITY®
Hispanic or Latino14
Not Hispanic or Latino146
Unknown or Not Reported0
Race (NIH/OMB)
Race (NIH/OMB)(Participants)DEFINITY®
American Indian or Alaska Native1
Asian3
Native Hawaiian or Other Pacific Islander2
Black or African American32
White120
More than one race2
Unknown or Not Reported0
LVEF Group
LVEF Group(Participants)DEFINITY®
LVEF <30%45
LVEF 30-40%48
LVEF 41-50%27
LVEF >50%40
08

Study locations

15 sites
  • Banner University of Arizona Medical Center
    Tucson, Arizona 85724, United States
  • Cedars Sinai
    Los Angeles, California 90048, United States
  • University of California-Irvine
    Orange, California 92868, United States
  • UC San Diego
    San Diego, California 92037, United States
  • Alfieri Cardiology
    Wilmington, Delaware 19803, United States
  • Northwestern Medical Group
    Chicago, Illinois 60611, United States
  • Indiana University
    Bloomington, Indiana 46202, United States
  • Baptist Hospital
    Paducah, Kentucky 42003, United States
  • Mercy Unit Hospital
    Coon Rapids, Minnesota 55433, United States
  • Duke University Medical Center
    Durham, North Carolina 27710, United States
  • University of Cincinnati Medical Center
    Cincinnati, Ohio 45219, United States
  • University of Oklahoma
    Oklahoma City, Oklahoma 73104, United States
  • Oregon Health and Sciences University
    Portland, Oregon 97240, United States
  • Albert Einstein Medical Center
    Philadelphia, Pennsylvania 19412, United States
  • Baylor Scott White Research Institute
    Temple, Texas 76501, United States
09

References and documents

Study documents

  • Study protocol · Aug 15, 2018
  • Statistical analysis plan · May 31, 2019

Documents are hosted by the registry — open the source record to download them.

Individual participant data

Plan to share: No

10

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Jan 28, 2021, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
11

Registry details

Key details

Study ID
NCT03719612
Lead sponsor
Lantheus Medical Imaging
Collaborators
Syneos Health
Responsible party
Sponsor
First posted
Oct 25, 2018
Start date
Dec 28, 2018
Primary completion
Jan 9, 2020
Completion
Jan 9, 2020
Results posted
Jan 7, 2021
Last update
Jan 28, 2021

Oversight

Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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