Noninvasive Real-time Intracardiac Pressure Measurements Using Subharmonic Ultrasound

NCT03245255 | Completed Phase 2 Results FDA Drug

• 1 other identifier: R21HL130899
• Study Type: interventional
• Target: 80
• Locations: 1 country
• Sites: 1

Brief Summary

This study will use contrast echocardiography to assess the accuracy of a new non-invasive imaging method for subharmonic aided pressure estimation (SHAPE) compared to simultaneously acquired intra-cardiac 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

Keywords

pressure measurements; blood pressure; contrast echocardiography; ventricular pressures; catheterization

Outcome Measures

Primary Outcomes (2)

• Agreement Between SHAPE and Pressure Catheter Measurements

  The Pearson correlation coefficient was computed between the simultaneously acquired subharmonic signal and pressure catheter data (i.e., waveforms) for each participant. The Pearson correlation coefficient was used for comparing waveforms given the underlying data and pressure values used for comparisons followed a normal distribution. Values reported will be the mean Pearson correlation coefficient values between the subharmonic waveforms and pressure catheter waveforms obtained.

  up to 1 day

• Error Between SHAPE and Pressure Catheter Measurements

  Based on the distribution of the differences in cardiac pressure values obtained using the SHAPE technique and the clinical pressure catheter, either a two-tailed paired t test (normal distribution) or Wilcoxon signed rank test (nonnormal distribution) was used to compare the SHAPE technique to the reference standard. Bonferroni corrections were used for multiple comparisons

  up to 1 day

Study Arms (1)

Sonazoid for pressure measurements

EXPERIMENTAL

48 µl of Sonazoid microbubbles (GE Healthcare, Oslo, Norway) will be co-infused at a rate of 0.024 µl/kg body weight/minute together with a 0.9% sodium chloride solution infused at a rate of at least 2 ml/min.

Drug: Sonazoid

Interventions

Sonazoid DRUG

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 Sonazoid 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.

Sonazoid for pressure measurements

Eligibility Criteria

• Age: 21 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Be scheduled for cardiac catheterization procedure.
• Be at least 18 years of age.
• Be medically stable.
• If a female of child-bearing potential, must have a negative pregnancy test.
• Be conscious and able to comply with study procedures.
• Have signed Informed Consent to participate in the study.

You may not qualify if:

• 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
• Females who are pregnant or nursing.
• Patients not scheduled for cardiac catheterization procedure.
• Patients who have received an investigational drug in the 30 days before, or will receive one within 72 h after, study drug administration.
• Patients currently on chemotherapy or with other primary cancers requiring treatment.
• Patients who are medically unstable, patients who are seriously or terminally ill, and patients whose clinical course is unpredictable.
• Patients with a history of anaphylactic allergy to eggs or egg products, manifested by one or more of the following symptoms: generalised urticaria, difficulty in breathing, swelling of the mouth and throat, hypotension, or shock. (Subjects with nonanaphylactic allergies to eggs or egg products may be enrolled in the study, but must be watched carefully for 1 h following the administration of SONAZOID).
• Patients with congenital heart defects.
• Patients with severe emphysema, pulmonary vasculitis, or a history of pulmonary emboli.
• Patients with respiratory distress syndrome or a contraindication to pharmacological vasodilator stress agents.
• Patients with thrombosis within the hepatic, portal, or mesenteric veins.

Sponsors & Collaborators

• Thomas Jefferson University: lead
• National Heart, Lung, and Blood Institute (NHLBI): collaborator
• GE Healthcare: collaborator

Study Sites (1)

Thomas Jefferson University and Thomas Jefferson University Hospital

Philadelphia, Pennsylvania, 19107, United States

Location

Related Publications (12)

• 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.

  PMID: 21989870 BACKGROUND

• 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.

  PMID: 22724314 BACKGROUND

• 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.

  PMID: 23347593 BACKGROUND

• 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.

  PMID: 22561300 BACKGROUND

• 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.

  PMID: 22239898 BACKGROUND

• 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.

  PMID: 23525208 BACKGROUND

• 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.

  PMID: 16060506 BACKGROUND

• 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.

  PMID: 21842580 BACKGROUND

• 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.

  PMID: 10320317 BACKGROUND

• 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.

  PMID: 24856899 BACKGROUND

• 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. Evaluation of Intracardiac Pressures Using Subharmonic-aided Pressure Estimation with Sonazoid Microbubbles. Radiol Cardiothorac Imaging. 2024 Feb;6(1):e230153. doi: 10.1148/ryct.230153.

  PMID: 38358329 DERIVED

• 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.

  PMID: 35079778 DERIVED

MeSH Terms

Conditions

Heart Failure

Interventions

Sonazoid

Condition Hierarchy (Ancestors)

Heart Diseases; Cardiovascular Diseases

Results Point of Contact

• Title: Jaydev Dave
• Organization: Thomas Jefferson University

dave.jaydev@mayo.edu

2158684795

Study Officials

• Jaydev K Dave

  Thomas Jefferson University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 4, 2017
• First Posted: August 10, 2017
• Study Start: December 4, 2017
• Primary Completion: September 18, 2020
• Study Completion: June 7, 2023
• Last Updated: May 29, 2024
• Results First Posted: May 29, 2024

Record last verified: 2024-05

Data Sharing

• IPD Sharing: Will share
• Shared Documents: CSR
• Time Frame: 2018-08-01 (anticipated) or starting 6 months after publication
• Access Criteria: Accessible research platform

Locations

US (1)