Cardiac CatheterizationPhase 2NCT03243942

Noninvasive, Subharmonic Intra-Cardiac Pressure Measurement

A Phase 2 study testing Definity in people with Cardiac Catheterization and Blood Pressure, run by Thomas Jefferson University at 1 site in United States.

Completed

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

Official record

Search all trials

Trial summary

Who is it for?: Ages 21 years and older
Conditions the study is for: Cardiac Catheterization, Blood Pressure, Heart Ventricles
What is being tested?: Definity
Type of treatment: Injection or infusion
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 56 participants
Where: 1 siteUnited States
Study dates: 1 Jun 2017to 26 Jun 2019
Phase: Phase 2
Are there results?: None posted in the registry

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

Who may be able to join

Be scheduled for a cardiac catheterization procedure
Adult patients over the age of 21
Acceptable baseline echocardiographic images in the supine position
If a female of child-bearing potential, must have a negative pregnancy test
Provide written informed consent

Who cannot join

Clinically unstable patients, e.g., those who are clinically in decompensated heart failure or having active chest pain or presenting for admission with an unstable anginal syndrome
Patients in whom introduction of a catheter into the left ventricle is contraindicated or would potentially be dangerous, e.g., patients with active ventricular arrhythmias or with significant aortic valve stenosis where crossing the aortic valve may be difficult and not clinically necessary
Patients with anatomic right-to-left, bi-directional, or transient right-to-left cardiac shunts where Definity could traverse as a bolus
Patients with known hypersensitivity to Definity
Females who are pregnant or nursing

Trial locations and contacts

1 site in 1 country.

United States1 site

Thomas Jefferson University and Thomas Jefferson University Hospital
Philadelphia, Pennsylvania, 19107

Other trials in United States

About this study

The fundamental hypothesis of this project is that real-time intracardiac pressures can be monitored and quantified noninvasively in humans using a novel contrast-enhanced ultrasound technique called subharmonic-aided pressure estimation (SHAPE).This study will use contrast echocardiography to assess the accuracy of SHAPE compared to simultaneously acquired intracardiac pressures measured invasively during cardiac catheterization. This study is designed to verify that contrast echocardiography using the SHAPE method, already proven in a canine model and tested in a human pilot study can be used as a surrogate for cardiac catheterization with sufficient accuracy to allow clinical applicability in humans.

Conditions: Cardiac Catheterization, Blood Pressure, Heart Ventricles, Echocardiography, Heart Failure
Being tested: Definity
Keywords: pressure measurements, blood pressure, contrast echocardiography, ventricular pressures, catheterization
Medical subject headings: Heart Failure

What participants receive

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

DefinityDrug
Whenever a patient undergoes cardiac catheterization, which routinely includes intracardiac pressure monitoring using a pressure catheter, as part of their standard clinical care and agrees to participate in the study, we will acquire research data. With Definity infusion, SHAPE algorithm will be initiated to determine optimum acoustic pressure. Then, at the optimum acoustic pressure SHAPE specific data will be acquired from the cardiac chambers and aorta synchronously with the pressures recorded by the catheter (as a part of the patient's standard of care). After acquiring the ultrasound imaging data, the remainder of the heart catheterization will be completed by the attending cardiologist according to the patients' standard of care.

Study groups in NCT03243942
Study group	Role	What they receive
Definity for pressure measurements	Experimental	2 vials of activated Definity mixed with 50 ml saline. As per manufacturer's recommendation the infusion rate may vary between 4-10 ml/min (to provide diagnostic intracardiac contrast visibility). Receives: Drug: Definity

What is being measured

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

Agreement between SHAPE and pressure catheter measurements
Correlation
Measured: up to 1 day
Error between SHAPE and pressure catheter measurements
ANOVA/Post-hoc comparisons
Measured: up to 1 day

Timeline

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

1 Jun 201726 Jun 2019

First posted9 Aug 2017
Study start1 Jun 2017
Primary completion26 Jun 2019
Study completion26 Jun 2019

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Publications (12)Papers the sponsor has linked to this study.
Other trials for Cardiac CatheterizationStudies of the same condition, open and under way.
More trials run by Thomas Jefferson UniversityThe sponsor's other registered studies.
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 2
Primary purpose: Diagnosis
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Enrolment: 56 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT03243942
Sponsor's protocol ID: 15SDG25740015
Status last verified: Jul 2019
First submitted: 3 Aug 2017
Last updated: 10 Jul 2019
Results posted: No
Data monitoring committee: No
FDA-regulated drug: Yes
FDA-regulated device: No
Individual data sharing: Yes: This project will generate pressure values in the aorta, and left and right ventricles using the proposed research method (i.e., SHAPE) and using the standard of care (i.e., catheter based pressure values). Additionally peripheral and central pressures will be generated. All of the pressure values will be made available. Further, all ultrasound data obtained for SHAPE measurements will be made available after anonymizing the data-set to remove any patient information.

Publications

Dave JK, Halldorsdottir VG, Eisenbrey JR, Liu JB, McDonald ME, Dickie K, Leung C, Forsberg F. Noninvasive estimation of dynamic pressures in vitro and in vivo using the subharmonic response from microbubbles. IEEE Trans Ultrason Ferroelectr Freq Control. 2011 Oct;58(10):2056-66. doi: 10.1109/TUFFC.2011.2056.
PubMed 21989870
Dave JK, Halldorsdottir VG, Eisenbrey JR, Forsberg F. Processing of subharmonic signals from ultrasound contrast agents to determine ambient pressures. Ultrason Imaging. 2012 Apr;34(2):81-92. doi: 10.1177/016173461203400202.
PubMed 22724314
Dave JK, Halldorsdottir VG, Eisenbrey JR, Merton DA, Liu JB, Machado P, Zhao H, Park S, Dianis S, Chalek CL, Thomenius KE, Brown DB, Forsberg F. On the implementation of an automated acoustic output optimization algorithm for subharmonic aided pressure estimation. Ultrasonics. 2013 Apr;53(4):880-8. doi: 10.1016/j.ultras.2012.12.010. Epub 2013 Jan 2.
PubMed 23347593
Dave JK, Halldorsdottir VG, Eisenbrey JR, Raichlen JS, Liu JB, McDonald ME, Dickie K, Wang S, Leung C, Forsberg F. Subharmonic microbubble emissions for noninvasively tracking right ventricular pressures. Am J Physiol Heart Circ Physiol. 2012 Jul;303(1):H126-32. doi: 10.1152/ajpheart.00560.2011. Epub 2012 May 4.
PubMed 22561300
Dave JK, Halldorsdottir VG, Eisenbrey JR, Raichlen JS, Liu JB, McDonald ME, Dickie K, Wang S, Leung C, Forsberg F. Noninvasive LV pressure estimation using subharmonic emissions from microbubbles. JACC Cardiovasc Imaging. 2012 Jan;5(1):87-92. doi: 10.1016/j.jcmg.2011.08.017.
PubMed 22239898
Eisenbrey JR, Dave JK, Halldorsdottir VG, Merton DA, Miller C, Gonzalez JM, Machado P, Park S, Dianis S, Chalek CL, Kim CE, Baliff JP, Thomenius KE, Brown DB, Navarro V, Forsberg F. Chronic liver disease: noninvasive subharmonic aided pressure estimation of hepatic venous pressure gradient. Radiology. 2013 Aug;268(2):581-8. doi: 10.1148/radiol.13121769. Epub 2013 Mar 22.
PubMed 23525208
Forsberg F, Liu JB, Shi WT, Furuse J, Shimizu M, Goldberg BB. In vivo pressure estimation using subharmonic contrast microbubble signals: proof of concept. IEEE Trans Ultrason Ferroelectr Freq Control. 2005 Apr;52(4):581-3. doi: 10.1109/tuffc.2005.1428040.
PubMed 16060506
Halldorsdottir VG, Dave JK, Leodore LM, Eisenbrey JR, Park S, Hall AL, Thomenius K, Forsberg F. Subharmonic contrast microbubble signals for noninvasive pressure estimation under static and dynamic flow conditions. Ultrason Imaging. 2011 Jul;33(3):153-64. doi: 10.1177/016173461103300301.
PubMed 21842580
Shi WT, Forsberg F, Raichlen JS, Needleman L, Goldberg BB. Pressure dependence of subharmonic signals from contrast microbubbles. Ultrasound Med Biol. 1999 Feb;25(2):275-83. doi: 10.1016/s0301-5629(98)00163-x.
PubMed 10320317
Halldorsdottir VG, Dave JK, Eisenbrey JR, Machado P, Zhao H, Liu JB, Merton DA, Forsberg F. Subharmonic aided pressure estimation for monitoring interstitial fluid pressure in tumours--in vitro and in vivo proof of concept. Ultrasonics. 2014 Sep;54(7):1938-44. doi: 10.1016/j.ultras.2014.04.022. Epub 2014 May 6.
PubMed 24856899
Esposito C, Machado P, McDonald ME, Savage MP, Fischman D, Mehrotra P, Cohen IS, Ruggiero N 2nd, Walinsky P, Vishnevsky A, Dickie K, Davis M, Forsberg F, Dave JK. Noninvasive Evaluation of Cardiac Chamber Pressures Using Subharmonic-Aided Pressure Estimation With Definity Microbubbles. JACC Cardiovasc Imaging. 2023 Feb;16(2):224-235. doi: 10.1016/j.jcmg.2022.09.013. Epub 2022 Nov 16.
PubMed 36648035
Esposito C, Machado P, Cohen IS, Mehrotra P, Savage M, Fischman D, Davis M, Ruggiero N, Walinsky P, McDonald ME, Dickie K, Forsberg F, Dave JK. Comparing Central Aortic Pressures Obtained Using a SphygmoCor Device to Pressures Obtained Using a Pressure Catheter. Am J Hypertens. 2022 May 10;35(5):397-406. doi: 10.1093/ajh/hpac010.
PubMed 35079778

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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All Cardiac Catheterization trials

Study at a glance

From the registry record, last updated by the sponsor on 10 Jul 2019. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Noninvasive, Subharmonic Intra-Cardiac Pressure Measurement
ClinicalTrials.gov ID: NCT03243942
Acronym / sponsor ID: 15SDG25740015
Conditions: Cardiac Catheterization, Blood Pressure, Heart Ventricles, Echocardiography, Heart Failure
Keywords: pressure measurements, blood pressure, contrast echocardiography, ventricular pressures, catheterization
Phase: Phase 2
Study type: Interventional
Recruitment status: Completed
Enrolment: 56 participants (actual)
Lead sponsor: Thomas Jefferson UniversityUniversity, hospital or other
Collaborators: American Heart Association, Lantheus Medical Imaging
Study start: 1 Jun 2017 (actual)
Primary completion: 26 Jun 2019 (actual)
Study completion: 26 Jun 2019 (actual)
First posted: 9 Aug 2017 (actual)
Results: Not posted in the source record

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 for pressure measurements	Experimental	Drug: Definity2 vials of activated Definity mixed with 50 ml saline. As per manufacturer's recommendation the infusion rate may vary between 4-10 ml/min (to provide diagnostic intracardiac contrast visibility).

Who may qualify

Ages: 21 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (5 listed)

Be scheduled for a cardiac catheterization procedure
Adult patients over the age of 21
Acceptable baseline echocardiographic images in the supine position
If a female of child-bearing potential, must have a negative pregnancy test
Provide written informed consent

Key exclusion criteria (5 listed)

Clinically unstable patients, e.g., those who are clinically in decompensated heart failure or having active chest pain or presenting for admission with an unstable anginal syndrome
Patients in whom introduction of a catheter into the left ventricle is contraindicated or would potentially be dangerous, e.g., patients with active ventricular arrhythmias or with significant aortic valve stenosis where crossing the aortic valve may be difficult and not clinically necessary
Patients with anatomic right-to-left, bi-directional, or transient right-to-left cardiac shunts where Definity could traverse as a bolus
Patients with known hypersensitivity to Definity
Females who are pregnant or nursing

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
DefinityWhenever a patient undergoes cardiac catheterization, which routinely includes intracardiac pressure monitoring using a pressure catheter, as part of their standard clinical care and agrees to participate in the study, we will acquire research data. With Definity infusion, SHAPE algorithm will be initiated to determine optimum acoustic pressure. Then, at the optimum acoustic pressure SHAPE specific data will be acquired from the cardiac chambers and aorta synchronously with the pressures recorded by the catheter (as a part of the patient's standard of care). After acquiring the ultrasound imaging data, the remainder of the heart catheterization will be completed by the attending cardiologist according to the patients' standard of care.	Drug	Definity for pressure measurements

Primary outcome

Agreement between SHAPE and pressure catheter measurements
Time frame: up to 1 day
Correlation
Error between SHAPE and pressure catheter measurements
Time frame: up to 1 day
ANOVA/Post-hoc comparisons

Results and safety

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 10 Jul 2019.
Background: PubMed 21989870Dave JK, Halldorsdottir VG, Eisenbrey JR, Liu JB, McDonald ME, Dickie K, Leung C, Forsberg F. Noninvasive estimation of dynamic pressures in vitro and in vivo using the subharmonic response from microbubbles. IEEE Trans Ultrason Ferroelectr Freq Control. 2011 Oct;58(10):2056-66. doi: 10.1109/TUFFC.2011.2056.
Background: PubMed 22724314Dave JK, Halldorsdottir VG, Eisenbrey JR, Forsberg F. Processing of subharmonic signals from ultrasound contrast agents to determine ambient pressures. Ultrason Imaging. 2012 Apr;34(2):81-92. doi: 10.1177/016173461203400202.
Background: PubMed 23347593Dave JK, Halldorsdottir VG, Eisenbrey JR, Merton DA, Liu JB, Machado P, Zhao H, Park S, Dianis S, Chalek CL, Thomenius KE, Brown DB, Forsberg F. On the implementation of an automated acoustic output optimization algorithm for subharmonic aided pressure estimation. Ultrasonics. 2013 Apr;53(4):880-8. doi: 10.1016/j.ultras.2012.12.010. Epub 2013 Jan 2.
Background: PubMed 22561300Dave JK, Halldorsdottir VG, Eisenbrey JR, Raichlen JS, Liu JB, McDonald ME, Dickie K, Wang S, Leung C, Forsberg F. Subharmonic microbubble emissions for noninvasively tracking right ventricular pressures. Am J Physiol Heart Circ Physiol. 2012 Jul;303(1):H126-32. doi: 10.1152/ajpheart.00560.2011. Epub 2012 May 4.
Background: PubMed 22239898Dave JK, Halldorsdottir VG, Eisenbrey JR, Raichlen JS, Liu JB, McDonald ME, Dickie K, Wang S, Leung C, Forsberg F. Noninvasive LV pressure estimation using subharmonic emissions from microbubbles. JACC Cardiovasc Imaging. 2012 Jan;5(1):87-92. doi: 10.1016/j.jcmg.2011.08.017.
Background: PubMed 23525208Eisenbrey JR, Dave JK, Halldorsdottir VG, Merton DA, Miller C, Gonzalez JM, Machado P, Park S, Dianis S, Chalek CL, Kim CE, Baliff JP, Thomenius KE, Brown DB, Navarro V, Forsberg F. Chronic liver disease: noninvasive subharmonic aided pressure estimation of hepatic venous pressure gradient. Radiology. 2013 Aug;268(2):581-8. doi: 10.1148/radiol.13121769. Epub 2013 Mar 22.
Background: PubMed 16060506Forsberg F, Liu JB, Shi WT, Furuse J, Shimizu M, Goldberg BB. In vivo pressure estimation using subharmonic contrast microbubble signals: proof of concept. IEEE Trans Ultrason Ferroelectr Freq Control. 2005 Apr;52(4):581-3. doi: 10.1109/tuffc.2005.1428040.
Background: PubMed 21842580Halldorsdottir VG, Dave JK, Leodore LM, Eisenbrey JR, Park S, Hall AL, Thomenius K, Forsberg F. Subharmonic contrast microbubble signals for noninvasive pressure estimation under static and dynamic flow conditions. Ultrason Imaging. 2011 Jul;33(3):153-64. doi: 10.1177/016173461103300301.
Background: PubMed 10320317Shi WT, Forsberg F, Raichlen JS, Needleman L, Goldberg BB. Pressure dependence of subharmonic signals from contrast microbubbles. Ultrasound Med Biol. 1999 Feb;25(2):275-83. doi: 10.1016/s0301-5629(98)00163-x.
Background: PubMed 24856899Halldorsdottir VG, Dave JK, Eisenbrey JR, Machado P, Zhao H, Liu JB, Merton DA, Forsberg F. Subharmonic aided pressure estimation for monitoring interstitial fluid pressure in tumours--in vitro and in vivo proof of concept. Ultrasonics. 2014 Sep;54(7):1938-44. doi: 10.1016/j.ultras.2014.04.022. Epub 2014 May 6.
Derived from this study: PubMed 36648035Esposito C, Machado P, McDonald ME, Savage MP, Fischman D, Mehrotra P, Cohen IS, Ruggiero N 2nd, Walinsky P, Vishnevsky A, Dickie K, Davis M, Forsberg F, Dave JK. Noninvasive Evaluation of Cardiac Chamber Pressures Using Subharmonic-Aided Pressure Estimation With Definity Microbubbles. JACC Cardiovasc Imaging. 2023 Feb;16(2):224-235. doi: 10.1016/j.jcmg.2022.09.013. Epub 2022 Nov 16.
Derived from this study: PubMed 35079778Esposito C, Machado P, Cohen IS, Mehrotra P, Savage M, Fischman D, Davis M, Ruggiero N, Walinsky P, McDonald ME, Dickie K, Forsberg F, Dave JK. Comparing Central Aortic Pressures Obtained Using a SphygmoCor Device to Pressures Obtained Using a Pressure Catheter. Am J Hypertens. 2022 May 10;35(5):397-406. doi: 10.1093/ajh/hpac010.
Individual participant dataSharing planned: Yes. This project will generate pressure values in the aorta, and left and right ventricles using the proposed research method (i.e., SHAPE) and using the standard of care (i.e., catheter based pressure values). Additionally peripheral and central pressures will be generated. All of the pressure values will be made available. Further, all ultrasound data obtained for SHAPE measurements will be made available after anonymizing the data-set to remove any patient information.

Related trials for Cardiac Catheterization

Not yet recruiting
NHLBI SESAME (SEptal Scoring Along Midline Endocardium) Multi-Center Prospective Study Using Improvised Off-Label Devices
Hypertrophic Cardiomyopathy, Left Ventricular Outflow Obstruction
Not yet recruiting
Novel Wearable Device for Heart Failure Management
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RecruitingPhase 4
Propofol-Ketamine Versus Sevoflurane for Laryngeal Mask Anesthesia in Pediatric Cardiac Catheterization
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RecruitingObservational study
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RecruitingObservational study
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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.

Jaydev Dave principal investigator

Thomas Jefferson University

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

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Definity in people with Cardiac Catheterization and Blood Pressure, run by Thomas Jefferson University at 1 site 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 5 inclusion and 5 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 10 Jul 2019. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

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

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

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?

Agreement between SHAPE and pressure catheter measurements (time frame: up to 1 day). The study lists 2 primary outcomes in all. 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 NCT03243942, which also lists 12 linked publications.

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 10 Jul 2019.