Cardiac DiseasePhase 3BENEFIT2NCT03719612

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

A Phase 3 study testing DEFINITY® in people with Cardiac Disease, run by Lantheus Medical Imaging at 15 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial 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. Read more about this study

Who is it for?: Ages 18 years and older
Conditions the study is for: Cardiac Disease
What is being tested?: DEFINITY®
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 160 participants
Where: 15 sitesUnited States
Study dates: 28 Dec 2018to 9 Jan 2020
Phase: Phase 3
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 years and older
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

Men and women ≥ 18 years of age in sinus rhythm
Able to communicate effectively with trial personnel
LVEF measurements obtained via 2D Echo with or without contrast obtained within 6 months prior to enrollment (Day 0)
Has provided signed informed consent after receiving a verbal and written explanation of this clinical trial

Who cannot join

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.
Women of child-bearing potential are excluded unless they:
are post-menopausal defined as amenorrhea ≥ 12 consecutive months, OR
have undergone successful surgical sterilization (hysterectomy, bilateral tubal ligation or bilateral oophorectomy), OR
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.
Current illness or pathology that would prevent undergoing investigational product administration due to a significant safety risk to the patient.

Show all 22Show fewer

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

Trial locations and contacts

15 sites in 1 country.

City, postcode or hospital

15 sites in 1 country

United States15 sites

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

Other trials in United States

About this study

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

Conditions: Cardiac Disease
Being tested: DEFINITY®
Keywords: Left Ventricular Ejection Fraction, DEFINITY®, Enhanced Echocardiogram, Cardiac Magnetic Resonance
Medical subject headings: Heart Diseases

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

DEFINITY®Drug
All subjects will receive a single dose of DEFINITY®

Study groups in NCT03719612
Study group	Role	What they receive
DEFINITY®	Experimental	Each patient will undergo an unenhanced ultrasound examination and a DEFINITY® contrast-enhanced ultrasound Receives: Drug: DEFINITY®

What is being measured

The primary outcome is the main question the study is designed to answer.

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

Secondary outcomes (5)

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

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

28 Dec 20189 Jan 2020

First posted25 Oct 2018
Study start28 Dec 2018
Primary completion9 Jan 2020
Study completion9 Jan 2020

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Other trials for Cardiac DiseaseStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 3
Primary purpose: Diagnosis
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Enrolment: 160 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT03719612
Sponsor's protocol ID: DEF-315
Acronym: BENEFIT2
Status last verified: Nov 2019
First submitted: 28 Sep 2018
Last updated: 28 Jan 2021
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No
FDA-regulated drug: Yes
FDA-regulated device: No
Individual data sharing: No

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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Efficacy, Safety, and Pharmacokinetics of Vericiguat in Pediatric Participants With Heart Failure Due to Left Ventricular Systolic Dysfunction (MK-1242-036)
Heart Failure, Left Ventricular Systolic Dysfunction
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Recruiting
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All Cardiac Disease trials

Study at a glance

From the registry record, last updated by the sponsor on 28 Jan 2021. Recruitment status is as the sponsor reported it: confirm with the study team.

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
ClinicalTrials.gov ID: NCT03719612
Acronym / sponsor ID: BENEFIT2 / DEF-315
Conditions: Cardiac Disease
Keywords: Left Ventricular Ejection Fraction, DEFINITY®, Enhanced Echocardiogram, Cardiac Magnetic Resonance
Phase: Phase 3
Study type: Interventional
Recruitment status: Completed
Enrolment: 160 participants (actual)
Lead sponsor: Lantheus Medical ImagingIndustry (pharma, biotech, devices)
Collaborators: Syneos Health
Study start: 28 Dec 2018 (actual)
Primary completion: 9 Jan 2020 (actual)
Study completion: 9 Jan 2020 (actual)
First posted: 25 Oct 2018 (actual)
Results: Posted 7 Jan 2021

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Study design

Primary purpose: Diagnosis
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Number of arms: 1

Arm	Type	Receives
DEFINITY®	Experimental	Drug: DEFINITY®Each patient will undergo an unenhanced ultrasound examination and a DEFINITY® contrast-enhanced ultrasound

Who may qualify

Ages: 18 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (4 listed)

Men and women ≥ 18 years of age in sinus rhythm
Able to communicate effectively with trial personnel
LVEF measurements obtained via 2D Echo with or without contrast obtained within 6 months prior to enrollment (Day 0)
Has provided signed informed consent after receiving a verbal and written explanation of this clinical trial

Key exclusion criteria (22 listed)

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.
Women of child-bearing potential are excluded unless they:
Current illness or pathology that would prevent undergoing investigational product administration due to a significant safety risk to the patient.
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).
Unstable cardiovascular status defined as:

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
DEFINITY®All subjects will receive a single dose of DEFINITY®	Drug	DEFINITY®

Primary outcome

Absolute Value of LVEF Percentage Differences From CMR by Blinded Reader
Time frame: 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.

5 secondary outcomes

Secondary Objective 1: Absolute Value of LVEF Percentage Differences From CMR by Blinded Reader for Sub-optimal Echocardiograms
Time frame: Up to 30 days between day of echocardiogram and CMR imaging
Secondary Objective 2: Absolute Value LVEF Percentage Differences From CMR Between Blinded Readers
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: Up to 30 days between day of echocardiograms and CMR imaging

Results and safety

Results posted to the registry on 7 Jan 2021, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
DEFINITY®	160	148

Primary outcome: Absolute Value of LVEF Percentage Differences From CMR by Blinded Reader

Time frame: Up to 30 days between day of echocardiograms and CMR imaging. Mean (Standard Deviation). Unit: Percent Ejection Fraction

Measure	Blinded Reader 1 n = 144	Blinded Reader 2 n = 144	Blinded Reader 3 n = 144
Echo Enhanced	5.70 (4.292)	5.88 (4.330)	5.03 (3.548)
Echo Unenhanced	6.08 (4.530)	6.00 (4.813)	5.36 (3.889)

Blinded Reader 1: Mean Difference (Final Values): -0.38, p = 0.358, t-test, 2 sided
Blinded Reader 2: Mean Difference (Final Values): -0.12, p = 0.804, t-test, 2 sided
Blinded Reader 3: Mean Difference (Final Values): -0.33, p = 0.371, t-test, 2 sided

Population analysed: Modified ITT Population

5 secondary outcomes are reported in the full results.

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).. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
DEFINITY®	1 of 160 (0.6%)	0 of 160 (0%)	0 of 160

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 28 Jan 2021.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Individual participant dataSharing planned: No

Related trials for Cardiac Disease

RecruitingPhase 2/3
Efficacy, Safety, and Pharmacokinetics of Vericiguat in Pediatric Participants With Heart Failure Due to Left Ventricular Systolic Dysfunction (MK-1242-036)
Heart Failure, Left Ventricular Systolic Dysfunction
RecruitingPhase 4
Efficacy and Safety of a Half-dose Bolus of r-SAK Prior to Primary PCI in ST-elevation Myocardial Infarction
ST Elevation Myocardial Infarction
Active, not recruitingPhase 4
Women's IschemiA TRial to Reduce Events In Non-ObstRuctive CAD
Coronary Artery Disease
Active, not recruiting
VOLT CE Mark Study
Atrial Arrhythmia, Atrial Fibrillation
Recruiting
SYMmetric Valve fraME Expansion To Reduce hYpoattenuated Leaflet Thickening After Balloon-expandable TAVI: the SYMMETRY Trial
Aortic Valve Stenosis and/or Insufficiency, Hypoattenuated Leaflet Thickening

Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

The record lists no contact. Use the official record to reach the sponsor.

15 sites in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing DEFINITY® in people with Cardiac Disease, run by Lantheus Medical Imaging at 15 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 4 inclusion and 22 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 28 Jan 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 15 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 7 Jan 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Absolute Value of LVEF Percentage Differences From CMR by Blinded Reader (time frame: Up to 30 days between day of echocardiograms and CMR imaging). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03719612.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Jan 2021.