DEF-315 Better Accuracy in Ejection Fraction (EF) Assessment With DEFINITY (BENEFIT2)

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

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.

Study Overview

• Status: Completed
• Conditions: Cardiac Disease
• Intervention / Treatment: Drug: DEFINITY®

• Study Type: Interventional
• Enrollment (Actual): 160
• Phase: Phase 3

Contacts and Locations

Study Locations

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

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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:

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).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: DIAGNOSTIC
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / 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®

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	Up to 30 days between day of echocardiograms and CMR imaging

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	Up to 30 days between day of echocardiogram and CMR imaging
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.	Up to 30 days between day of echocardiograms and CMR imaging
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.	Up to 30 days between day of echocardiogram and CMR imaging
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.	Up to 30 days between day of echocardiograms and CMR imaging
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.	Up to 30 days between day of echocardiograms and CMR imaging

Collaborators and Investigators

• Sponsor: Lantheus Medical Imaging
• Collaborators: Syneos Health

Study record dates

Study Major Dates

• Study Start (ACTUAL): December 28, 2018
• Primary Completion (ACTUAL): January 9, 2020
• Study Completion (ACTUAL): January 9, 2020

Study Registration Dates

• First Submitted: September 28, 2018
• First Submitted That Met QC Criteria: October 23, 2018
• First Posted (ACTUAL): October 25, 2018

Study Record Updates

• Last Update Posted (ACTUAL): January 28, 2021
• Last Update Submitted That Met QC Criteria: January 7, 2021
• Last Verified: November 1, 2019

More Information

Terms related to this study

• Keywords: Cardiac Magnetic Resonance; Left Ventricular Ejection Fraction; DEFINITY®; Enhanced Echocardiogram
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Heart Diseases
• Other Study ID Numbers: DEF-315

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No