Study to Determine Safety and Dosage of OPTISON in Pediatric Participants

A Phase 4, Open-Label, Non-Randomized, Multicenter Study to Evaluate Safety and Efficacy of Intravenous Administration of OPTISON™ for Contrast- Enhanced Echocardiography in Pediatric Patients

Study to determine the safety and appropriate dosage of OPTISON in pediatric participants since OPTISON has been tested in adult participants only during the clinical development

Study Overview

• Status: Completed
• Conditions: Transthoracic Echocardiography; Suspected or Known Structural or Functional Cardiac Abnormality
• Intervention / Treatment: Drug: Optison

• Study Type: Interventional
• Enrollment (Actual): 39
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Phoenix, Arizona, United States, 85016
      • Phoenix Children's Hospital
  • California
    • Los Angeles, California, United States, 90027
      • Children's Hospital Los Angeles
  • Georgia
    • Augusta, Georgia, United States, 30912
      • MCG Health, Inc.
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Ann & Robert H. Lurie Children's Hospital of Chicago
  • Maryland
    • Baltimore, Maryland, United States, 21287
      • Johns Hopkins University School of Medicine
  • New York
    • Lake Success, New York, United States, 11042
      • Cohen Children's Medical Center of New York
  • Ohio
    • Cleveland, Ohio, United States, 44195
      • Cleveland Clinic Foundation
  • Texas
    • Houston, Texas, United States, 77030
      • Baylor College of Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 9 years to 17 years (Child)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• The participant was between ≥9 and <18 years of age and weighs ≥20 kg.
• The participant was clinically indicated to undergo a transthoracic echocardiogram.
• The participant had a suboptimal non-contrast echocardiogram defined as ≥2 contiguous segments in any given view that cannot be visualized.
• The participant was able to comply with study procedures.
• A parent or legal guardian of the participant had signed and dated an informed consent form.
• Post-menarchal female participants must have had a negative urine pregnancy test at screening and at pre-dose on the day of OPTISON administration.
• Post-menarchal female participants must have been practicing abstinence, or be using an effective form of birth control (e.g., intrauterine device, oral contraceptives, contraceptive implants or injections, diaphragm with spermicide, cervical cap, or consort use of condom) for at least 30 days before being enrolled in the study

Exclusion Criteria:

• The participant was previously enrolled in this study.
• The participant received an investigational medicinal product within 30 days before or is scheduled to receive one from time of entry into this study until completion of the follow-up period proposed for this study.
• The participant had a known or suspected hypersensitivity to any of the components of OPTISON, blood, blood products, or albumin.
• The participant had pulmonary hypertension or unstable cardiopulmonary conditions.
• The participant had severe liver disease based on medical history.
• The participant had a recent (<6 months) neurological event.
• The participant presented any clinically active, serious, life-threatening disease, with a life expectancy of less than 1 month or where study participation may compromise the management of the participant or other reason that in the judgment of the investigator makes the participant unsuitable for participation in the study.
• The participant was a pregnant or lactating female, or was a female of childbearing potential not using an acceptable form of birth control (negative urine pregnancy test was also required).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Body Weight Group <=40 kg: OPTISON; Participants with body weight greater than or equal to (>=) 20 to less than or equal to (<=) 28 kilograms (kg) received OPTISON 0.1 milliliter (mL; dose level 1) or 0.2 mL (dose level 2); and participants with body weight greater than (>) 28 to <=40 kg received OPTISON 0.2 mL (dose level 1) or 0.3 mL (dose level 2) intravenous (IV) injection, 10 minutes apart on Day 1. The maximum allowed cumulative dose for body weight >=20 to <=28 kg and >28 to <=40 kg was 1.0 mL and 1.5 mL per dose level, respectively. The treated subjects received both dose levels. Per protocol, up to 3 injections per dose level were allowed for acquiring different imaging views. A maximum of 2 injections was recorded in the treated population.	Drug: Optison; Optison is administered intravenously; Other Names: Perflutren Microspheres Injectable Suspension, USP
Experimental: Body Weight Group >40 kg: OPTISON; Participants with body weight >40 kg received OPTISON 0.2 (dose level 1) or 0.4 mL (dose level 2) IV injection, 10 minutes apart on Day 1. The maximum allowed cumulative dose was 1.8 mL per dose level. The treated subjects received both dose levels. Per protocol, up to 3 injections per dose level were allowed for acquiring different imaging views. A maximum of 2 injections was recorded in the treated population.	Drug: Optison; Optison is administered intravenously; Other Names: Perflutren Microspheres Injectable Suspension, USP

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mean Total Visualization Score of Qualitative Endocardial Border Delineation (EBD) of the 12 Segments of the Left Ventricle (LV) Wall in Standard Apical 4-chamber (A4C) and Apical 2-chamber (A2C)	Visualization of each of the 12 segments of the LV wall in standard A4C and A2C views were measured by the qualitative EBD visualization scale: score 0 =no visualization of the LV endocardial border; 1 =poor visualization; 2 =fair visualization; 3 =good/optimal visualization. The total LV EBD score was calculated as the sum of the individual scores assigned to each of the 12 LV wall segment and the total score ranged from 0 (no visualization of the LV endocardial border) to 36 (good/optimal visualization). A higher score indicated better visualization. The total score of qualitative EBD visualization scale were reported by reader (independent blinded), non-contrast and dose levels.	Images were captured during the study echocardiogram (0 to 30 minutes) on Day 1 and blinded image evaluations (BIE) were carried out at the study core laboratory following image transfer

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Treatment-emergent Adverse Events (TEAEs)	An Adverse Event (AE) was any untoward medical occurrence in a participant administered a pharmaceutical product and which did not necessarily had to have causal relationship with treatment. TEAEs were defined as AEs that starts or worsens at or after the time of first dosing of OPTISON.	0- 72 hours
Change From Baseline in Systolic and Diastolic Blood Pressure	Systolic and diastolic blood pressure were measured from the arm contra-lateral to the site of OPTISON administration whenever possible and before measurement, participants rested for at least 5 minutes (if possible).	Baseline (pre-dose), and at 10 and 60 minutes post last dose on Day 1
Change From Baseline in Heart Rate	Before heart rate was measured, participants rested for at least 5 minutes (if possible).	Baseline (pre-dose), and at 10 and 60 minutes post last dose on Day 1
Change From Baseline in Respiratory Rate	Before respiratory rate was measured, participants rested for at least 5 minutes (if possible).	Baseline (pre-dose), and at 10 and 60 minutes post last dose on Day 1
Change From Baseline in Oxygen Saturation as Measured by Pulse Oximetry	Oxygen saturation was measured by pulse oximetry. Before oxygen saturation was measured, participants rested for at least 5 minutes (if possible).	Baseline (pre-dose), and at 10 and 60 minutes post last dose on Day 1
Number of Participants With Clinically Significant Abnormality in Physical Examination Findings	Participants underwent assessments including general appearance, respiratory, cardiovascular and neurological (motor function, level of consciousness, sensory function) examination. Any abnormal clinically significant physical examination findings were based on investigator decision.	From first dose (Day 1) of study drug to 60 minutes post last dose on Day 1
Change From Baseline in 12-lead Electrocardiograms (ECGs) Parameters	Change from baseline in PR, QRS, QT, Bazett's formula corrected QT (QTcB), Fridericia's formula corrected QT (QTcF) and RR intervals expressed in millisecond (ms) were reported.	Baseline (pre-dose), and at 10 and 30 minutes post last dose on Day 1
Number of Participants by Degree of Left Ventricular Opacification (LVO) Assessed by Visual Peak Contrast Intensity	LVO peak contrast intensity was determined by readers (independent blinded) using a categorical scale as None, Low, Medium, High or Blooming, where, None = Absence of contrast signal; Low = Limited capacity to make a diagnostic assessment; Presence of contrast signal does not improve diagnostic interpretability to a great degree; Medium = Good capacity to make a diagnostic assessment; Contrast signal facilitates diagnostic interpretability to a good degree; High = Optimal capacity to make a diagnostic assessment; Contrast signal facilitates diagnostic interpretability to a high degree; Blooming = Oversaturation of the signal disrupts diagnostic interpretability. Tissue boundaries become challenging to delineate. There may be excessive acoustic shadowing in the far-field of the image. Number of participants by degree of LVO assessed by visual peak contrast intensity was presented by readers and dose levels.	Images were captured during the study echocardiogram (0 to 30 minutes) on Day 1 and blinded image evaluations (BIE) were carried out at the study core laboratory following image transfer
Number of Participants by Grade of Left Ventricular Opacification (LVO) Assessed by Peak Left Ventricular (LV) Contrast Filling	Peak LV contrast filling for LVO was categorized as: 0 = none (0 percent [%] filling); 1 = faint (around 33% filling); 2 = intermediate (around 67% filling); 3 = full (100% filling) and data were presented by readers (independent blinded) and dose levels.	Images were captured during the study echocardiogram (0 to 30 minutes) on Day 1 and blinded image evaluations (BIE) were carried out at the study core laboratory following image transfer
Number of Participants by Contrast Enhancement Duration in the Left Ventricular (LV) Chamber	Contrast enhancement duration was determined from the time the contrast appeared in the LV to the time the contrast almost dissipated from the left chamber. 3 independent blinded reader performed evaluation.	Images were captured during the study echocardiogram (0 to 30 minutes) on Day 1 and blinded image evaluations (BIE) were carried out at the study core laboratory following image transfer
Number of Participants by Diagnostic Confidence of Left Ventricular Endocardial Border Delineation (LV EBD) and Wall Motion for Contrast and Non-Contrast Enhanced Images	Diagnostic confidence for the assessment of LV EBD and wall motion was scored for non-contrast and OPTISON-enhanced echocardiographic acquisitions separately using a 4-point scale which ranged from ranged 0 to 4, where 0 = no confidence, 1 = low confidence, 2 = moderate confidence, 3 = high confidence. A higher score indicates better confidence level. Data were presented by reader (independent blinded), non-contrast and dose levels.	Images were captured during the study echocardiogram (0 to 30 minutes) on Day 1 and blinded image evaluations (BIE) were carried out at the study core laboratory following image transfer
Number of Participants by Diagnostic Confidence of Left Ventricular Ejection Fraction (LVEF) for Non-contrast and OPTISON Enhanced Echocardiography	Diagnostic confidence for the evaluation of LVEF was calculated using the formula: (end diastole volume - end systole volume)/(end diastole volume) was scored for non-contrast and OPTISON-enhanced echocardiographic acquisitions separately using a 4-point scale which ranged from 0 to 3, where 0 = no confidence, 1 = low confidence, 2 = moderate confidence, 3 = high confidence. A higher score indicates better confidence level. Data were presented by reader (independent blinded), non-contrast and dose levels.	Images were captured during the study echocardiogram (0 to 30 minutes) on Day 1 and blinded image evaluations (BIE) were carried out at the study core laboratory following image transfer

Other Outcome Measures

Outcome Measure	Time Frame
Comparison of diagnostic confidence of LV EBD and wall motion between non-contrast and OPTISON-enhanced echocardiography at various doses.	72 hours
Comparison of diagnostic confidence in the evaluation of LVEF between non-contrast and OPTISON-enhanced echocardiography.	72 hours

Collaborators and Investigators

• Sponsor: GE Healthcare
• Collaborators: Laboratory Corporation of America
• Investigators: Study Director: David Thompson, MD, PhD, GE Healthcare

Study record dates

Study Major Dates

• Study Start (Actual): December 1, 2020
• Primary Completion (Actual): March 30, 2023
• Study Completion (Actual): March 30, 2023

Study Registration Dates

• First Submitted: October 31, 2018
• First Submitted That Met QC Criteria: November 13, 2018
• First Posted (Actual): November 14, 2018

Study Record Updates

• Last Update Posted (Actual): May 17, 2024
• Last Update Submitted That Met QC Criteria: May 13, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Keywords: Child; Left ventricular ejection fraction (LVEF); Contrast-enhanced echocardiography (CE-ECHO); Transthoracic echocardiogram; Left ventricular opacification (LVO); Left ventricular endocardial border delineation (LV EBD)
• Additional Relevant MeSH Terms: Congenital Abnormalities
• Other Study ID Numbers: GE-191-008

Drug and device information, study documents

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