Hypoxic-Ischemic EncephalopathyPhase 3NCT03549520
CEUS Evaluation of Hypoxic Ischemic Injury
A Phase 3 study testing Sulfur hexafluoride lipid-type A microspheres in people with Hypoxic-Ischemic Encephalopathy and Brain Ischemia Hypoxia, run by Children's Hospital of Philadelphia at 1 site in United States.
Trial summary
Neonates presenting with neurologic symptoms require rapid, non-invasive imaging with high spatial resolution and tissue contrast. The purpose of this study is to evaluate brain perfusion using contrast-enhanced ultrasound CEUS in bedside monitoring of neonates and infants with hypoxic ischemic injury (HII). Read more about this study
- Who is it for?
- Ages 1 minute to 18 months
- Conditions the study is for
- Hypoxic-Ischemic Encephalopathy, Brain Ischemia Hypoxia
- What is being tested?
- Sulfur hexafluoride lipid-type A microspheres
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 1 participants
- Where
- 1 siteUnited States
- Study dates
- 1 Dec 2020to 7 May 2024
- 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 1 minute to 18 months
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- Males and females aged 1.5 years or younger with open fontanelles and known or suspected hypoxic ischemic injury.
- Post menstrual age of 34 weeks or older
- Patient in the Children's Hospital of Philadelphia (CHOP) Neonatal Intensive Care Unit (NICU) or Pediatric Intensive Care Unit (PICU)
- Parental permission
Who cannot join
- Medical history of Lumason hypersensitivity
- Hemodynamic instability as defined by rapid escalation of cardiopulmonary support in the past 12-24 hours, as defined by the clinical care team including ≥ 1 intensive care physician not part of the study team
- Pulmonary insufficiency as defined by fraction of inspired oxygen (FiO2) requirements of > 40% and/or subjects with pulmonary hypertension requiring nitric oxide
Trial locations and contacts
1 site in 1 country.
United States1 site
The Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, 19104
About this study
Official title: Improved Diagnosis and Prognostication of Hypoxic Ischemic Injury in Neonates and Infants Using Contrast-Enhanced Ultrasound
Neonates presenting with neurologic symptoms require rapid, non-invasive imaging with high spatial resolution and tissue contrast. The purpose of this study is to evaluate brain perfusion using contrast-enhanced ultrasound CEUS in bedside monitoring of neonates and infants with hypoxic ischemic injury (HII). Investigational CEUS scan will be performed separately from clinically indicated conventional US, in the ICU. Subjects will be scanned with CEUS at two different time-points (at the time HII is first suspected or diagnosed and at time of MRI scan), separately from clinically indicated ultrasound. The CEUS scan will be interpreted by the sponsor-investigator.
The study will be conducted at one site, The Children's Hospital of Philadelphia. It is expected that up to 100 subjects will be enrolled per year, for up to two years, for a total enrollment of up to 200 subjects.
Read the detailed description
Contrast-enhanced ultrasonography (CEUS) is a novel imaging technique in which gas-filled microbubbles, smaller than red blood cells, generate increased signal due to the acoustic impedance mismatch. Injection of ultrasound contrast agents into blood increase the echogenicity, allowing enhanced visualization of a blood vessel. Ultrasound contrast agents have been approved for use in Europe for almost two decades. In the case of SonoVue (now called LumasonTM), a second-generation lipid/sulfur hexafluoride US contrast agent (Bracco, Milan, Italy), European Union approved its intravenous use in adults in 2001. The FDA in the United States just recently approved the use of LumasonTM for evaluation of focal hepatic lesions in pediatric population in 2016, and very recently (Jan 2017) approved its use in children for the evaluation of the urinary tract in pediatric patients with known or suspected vesicoureteral reflux. For the remainder of clinical applications, the ultrasound contrast agents are being used off-label in both Europe and the United States.
There is already good evidence in the literature that CEUS may be very valuable in children, and that is why it is routinely performed off-label for this purpose in the USA. However, there are ways in which it could be improved, and more studies are needed to definitively establish its diagnostic performance.
Sulfur hexafluoride lipid-type A microspheres (LumasonTM, Bracco Inc) is an FDA-approved ultrasound contrast agent. The study duration per subject will be approximately 15 minutes including the time to prepare LumasonTM contrast agent and perform the CEUS, as well as the 60 minute monitoring period after the first and second injection of LumasonTM. CEUS will be performed at the time HII is first suspected or diagnosed and within 24 hours of clinically indicated MRI (which occurs approximately on day 5 of life) for a total of two CEUS exams of 1 hour and 15-minute duration each. Study participation will be complete when the 60 minute monitoring period after the second CEUS is complete.
Injection of LumasonTM contrast agent will be performed via the existing peripheral intravenous line or central line using the FDA-recommended dose of up to 0.03 mg/kg. Contrast-agent injection will be performed twice per CEUS scan to ensure image quality and test reproducibility. In the case of more stable patients without an IV line, a peripheral IV line will be started to conduct the investigational CEUS. Two bolus injections will performed to evaluate for dynamic brain perfusion and several 2-minute cine clips as well as static images will be acquired during the exam.
Qualitative analysis with visual assessment and quantitative analysis of the acquired CEUS scans will be performed and interpreted by the PI. The scans will be assessed for diagnostic quality of images, artifacts encountered, and the presence of additional contributory diagnostic information.
- Being tested
- Sulfur hexafluoride lipid-type A microspheres
- Keywords
- Ultrasound, Contrast-enhanced ultrasound
- Medical subject headings
- Hypoxia-Ischemia, Brain
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Sulfur hexafluoride lipid-type A microspheresDrug
Injection of Sulfur hexafluoride lipid-type A microspheres (Lumason) contrast agent will be performed via the existing peripheral intravenous line using the FDA-recommended dose of 0.03 mg/kg.
| Study group | Role | What they receive |
|---|---|---|
| Contrast-enhanced Ultrasonography | Experimental | Intravenous administration of contrast agent Sulfur hexafluoride lipid-type A microspheres before performing contrast-enhanced ultrasound (CEUS). In pediatric patients, after reconstitution 0.03 mL per kg is administered intravenously. The weight-based dose of 0.03 mL per kg will be repeated one time during a single examination. Following each injection, an intravenous flush of 0.9% Sodium Chloride is injected. The study duration per subject will be approximately 15 minutes including the time to prepare the contrast agent and perform the CEUS, as well as the 60 minute monitoring period after the first and second injection of the contrast agent. Receives: Drug: Sulfur hexafluoride lipid-type A microspheres |
What is being measured
The primary outcome is the main question the study is designed to answer.
Detection of Brain Perfusion Abnormalities Using Contrast-enhanced Ultrasound
Comparison of brain perfusion between normal subjects (those with suspected or at risk of HII but turn out to be normal on imaging and clinical evaluation) versus HII patients
Measured: During contrast-enhanced ultrasound examination, up to 15 minutes.
Secondary outcomes (1)
Number of Participants With Completed Brain CEUS Exams, Categorized by Diagnostic-Quality Scoring System
Scoring system of non-diagnostic (1), moderate artifacts degrading diagnostic quality (2), mild artifacts without degradation of diagnostic quality (3), and diagnostic (4).
Measured: During contrast-enhanced ultrasound examination, up to 15 minutes.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Jun 2018
- Study start1 Dec 2020
- Primary completion7 May 2024
- Study completion7 May 2024
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.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Hypoxic-Ischemic EncephalopathyStudies of the same condition, open and under way.
- More trials run by Children's Hospital of PhiladelphiaThe 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 3
- Primary purpose
- Diagnosis
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 1 participants (actual)
Sponsor and investigators
- Lead sponsor
- Children's Hospital of Philadelphia
- Sponsor type
- University, hospital or other
- Collaborators
- Bracco Diagnostics, Inc
- Responsible party
- Principal investigator, Misun Hwang, MD, Children's Hospital of Philadelphia
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03549520
- Sponsor's protocol ID
- 18-014912
- Status last verified
- May 2025
- First submitted
- 25 May 2018
- Last updated
- 14 May 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Hwang M, Piskunowicz M, Darge K. Advanced Ultrasound Techniques for Pediatric Imaging. Pediatrics. 2019 Mar;143(3):e20182609. doi: 10.1542/peds.2018-2609.
PubMed 30808770
Study at a glance
From the registry record, last updated by the sponsor on 14 May 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Improved Diagnosis and Prognostication of Hypoxic Ischemic Injury in Neonates and Infants Using Contrast-Enhanced Ultrasound
- ClinicalTrials.gov ID
- NCT03549520
- Acronym / sponsor ID
- 18-014912
- Keywords
- Ultrasound, Contrast-enhanced ultrasound
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 1 participants (actual)
- Lead sponsor
- Children's Hospital of PhiladelphiaUniversity, hospital or other
- Collaborators
- Bracco Diagnostics, Inc
- Study start
- 1 Dec 2020 (actual)
- Primary completion
- 7 May 2024 (actual)
- Study completion
- 7 May 2024 (actual)
- First posted
- 8 Jun 2018 (actual)
- Results
- Posted 14 May 2025
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Neonates presenting with neurologic symptoms require rapid, non-invasive imaging with high spatial resolution and tissue contrast. The purpose of this study is to evaluate brain perfusion using contrast-enhanced ultrasound CEUS in bedside monitoring of neonates and infants with hypoxic ischemic injury (HII). Investigational CEUS scan will be performed separately from clinically indicated conventional US, in the ICU. Subjects will be scanned with CEUS at two different time-points (at the time HII is first suspected or diagnosed and at time of MRI scan), separately from clinically indicated ultrasound. The CEUS scan will be interpreted by the sponsor-investigator.
The study will be conducted at one site, The Children's Hospital of Philadelphia. It is expected that up to 100 subjects will be enrolled per year, for up to two years, for a total enrollment of up to 200 subjects.
Detailed description
Contrast-enhanced ultrasonography (CEUS) is a novel imaging technique in which gas-filled microbubbles, smaller than red blood cells, generate increased signal due to the acoustic impedance mismatch. Injection of ultrasound contrast agents into blood increase the echogenicity, allowing enhanced visualization of a blood vessel. Ultrasound contrast agents have been approved for use in Europe for almost two decades. In the case of SonoVue (now called LumasonTM), a second-generation lipid/sulfur hexafluoride US contrast agent (Bracco, Milan, Italy), European Union approved its intravenous use in adults in 2001. The FDA in the United States just recently approved the use of LumasonTM for evaluation of focal hepatic lesions in pediatric population in 2016, and very recently (Jan 2017) approved its use in children for the evaluation of the urinary tract in pediatric patients with known or suspected vesicoureteral reflux. For the remainder of clinical applications, the ultrasound contrast agents are being used off-label in both Europe and the United States.
There is already good evidence in the literature that CEUS may be very valuable in children, and that is why it is routinely performed off-label for this purpose in the USA. However, there are ways in which it could be improved, and more studies are needed to definitively establish its diagnostic performance.
Sulfur hexafluoride lipid-type A microspheres (LumasonTM, Bracco Inc) is an FDA-approved ultrasound contrast agent. The study duration per subject will be approximately 15 minutes including the time to prepare LumasonTM contrast agent and perform the CEUS, as well as the 60 minute monitoring period after the first and second injection of LumasonTM. CEUS will be performed at the time HII is first suspected or diagnosed and within 24 hours of clinically indicated MRI (which occurs approximately on day 5 of life) for a total of two CEUS exams of 1 hour and 15-minute duration each. Study participation will be complete when the 60 minute monitoring period after the second CEUS is complete.
Injection of LumasonTM contrast agent will be performed via the existing peripheral intravenous line or central line using the FDA-recommended dose of up to 0.03 mg/kg. Contrast-agent injection will be performed twice per CEUS scan to ensure image quality and test reproducibility. In the case of more stable patients without an IV line, a peripheral IV line will be started to conduct the investigational CEUS. Two bolus injections will performed to evaluate for dynamic brain perfusion and several 2-minute cine clips as well as static images will be acquired during the exam.
Qualitative analysis with visual assessment and quantitative analysis of the acquired CEUS scans will be performed and interpreted by the PI. The scans will be assessed for diagnostic quality of images, artifacts encountered, and the presence of additional contributory diagnostic information.
Study design
- Primary purpose
- Diagnosis
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Contrast-enhanced Ultrasonography | Experimental | Drug: Sulfur hexafluoride lipid-type A microspheresIntravenous administration of contrast agent Sulfur hexafluoride lipid-type A microspheres before performing contrast-enhanced ultrasound (CEUS). In pediatric patients, after reconstitution 0.03 mL per kg is administered intravenously. The weight-based dose of 0.03 mL per kg will be repeated one time during a single examination. Following each injection, an intravenous flush of 0.9% Sodium Chloride is injected. The study duration per subject will be approximately 15 minutes including the time to prepare the contrast agent and perform the CEUS, as well as the 60 minute monitoring period after the first and second injection of the contrast agent. |
Who may qualify
- Ages
- 1 minute to 18 months
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (4 listed)
- Males and females aged 1.5 years or younger with open fontanelles and known or suspected hypoxic ischemic injury.
- Post menstrual age of 34 weeks or older
- Patient in the Children's Hospital of Philadelphia (CHOP) Neonatal Intensive Care Unit (NICU) or Pediatric Intensive Care Unit (PICU)
- Parental permission
Key exclusion criteria (3 listed)
- Medical history of Lumason hypersensitivity
- Hemodynamic instability as defined by rapid escalation of cardiopulmonary support in the past 12-24 hours, as defined by the clinical care team including ≥ 1 intensive care physician not part of the study team
- Pulmonary insufficiency as defined by fraction of inspired oxygen (FiO2) requirements of > 40% and/or subjects with pulmonary hypertension requiring nitric oxide
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 |
|---|---|---|
| Sulfur hexafluoride lipid-type A microspheresInjection of Sulfur hexafluoride lipid-type A microspheres (Lumason) contrast agent will be performed via the existing peripheral intravenous line using the FDA-recommended dose of 0.03 mg/kg. | Drug | Contrast-enhanced Ultrasonography |
Primary outcome
Detection of Brain Perfusion Abnormalities Using Contrast-enhanced Ultrasound
Time frame: During contrast-enhanced ultrasound examination, up to 15 minutes.
Comparison of brain perfusion between normal subjects (those with suspected or at risk of HII but turn out to be normal on imaging and clinical evaluation) versus HII patients
1 secondary outcome
Number of Participants With Completed Brain CEUS Exams, Categorized by Diagnostic-Quality Scoring System
Time frame: During contrast-enhanced ultrasound examination, up to 15 minutes.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 May 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 30808770Hwang M, Piskunowicz M, Darge K. Advanced Ultrasound Techniques for Pediatric Imaging. Pediatrics. 2019 Mar;143(3):e20182609. doi: 10.1542/peds.2018-2609.
- Individual participant dataSharing planned: No
Related trials for Hypoxic-Ischemic Encephalopathy
Recruiting
Minimal Sedation Versus Standard Continuous Sedation After Out-of-Hospital Cardiac Arrest
Out-of-Hospital Cardiac Arrest, Hypoxic-Ischemic Brain Injury
RecruitingPhase 2
The PROTECT-HIE Pilot Trial
Hypoxic-ischemic Encephalopathy (HIE)
Recruiting
Neuro-MoD: Neuroplasticity With Motor Development
Perinatal Brain Injury
RecruitingPhase 2
A Dose Escalation Study of Levetiracetam in the Treatment of Neonatal Seizures
Neonatal Seizure, Neonatal Encephalopathy
Recruiting
Pediatric Influence of Cooling Duration on Efficacy in Cardiac Arrest Patients (P-ICECAP)
Cardiac Arrest, Out-Of-Hospital, Hypothermia, Induced
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.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Sulfur hexafluoride lipid-type A microspheres in people with Hypoxic-Ischemic Encephalopathy and Brain Ischemia Hypoxia, run by Children's Hospital of Philadelphia 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 4 inclusion and 3 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 14 May 2025. 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 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 14 May 2025). 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?
Detection of Brain Perfusion Abnormalities Using Contrast-enhanced Ultrasound (time frame: During contrast-enhanced ultrasound examination, up to 15 minutes.). 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 NCT03549520, which also lists 1 linked publication.
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 14 May 2025.