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CEUS Evaluation of Hypoxic Ischemic Injury

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. Identifier: NCT03549520
Recruitment Status : Recruiting
First Posted : June 8, 2018
Last Update Posted : March 8, 2019
Information provided by (Responsible Party):
Misun Hwang, MD, Children's Hospital of Philadelphia

Brief Summary:
The goal of the study is to perform off-label application of contrast enhanced ultrasound (CEUS) for diagnosis and monitoring of brain injury in neonates and infants. This study will recruit patients between 0-1 year in the neonatal intensive care unit or pediatric intensive care unit at Children's Hospital of Philadelphia who are already scheduled to receive a standard of care grayscale brain ultrasound scan. Lumason will be administered intravenously. The CEUS portion will immediately follow the standard of care brain ultrasound exam.

Condition or disease Intervention/treatment Phase
Hypoxic-Ischemic Encephalopathy Brain Ischemia Hypoxia Drug: Sulfur hexafluoride lipid-type A microspheres Phase 3

Detailed Description:

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. Hence, this is why we wish to perform this study.

All participants in this research study will have already scheduled standard of care brain ultrasound exam. The CEUS portion will immediately follow the standard of care brain ultrasound exam. The results of the CEUS will be reported as usual in the radiology report. The patient will be billed as per their standard clinical care (i.e. no additional costs associated with the research procedure).

A consent form signed by the patient's parents and/or legal guardian will be required to indicate agreement to participate in the study. Each parent and/or legal guardian of participant who agrees to participate will be asked to extend his/her already scheduled brain ultrasound exam by approximately 40 minutes, 10 minutes for the contrast ultrasound examination and 30 minutes for post examination monitoring of potential adverse events. Note that all CEUS exams will be performed at bedside in the neonatal and pediatric intensive care units. No transport will be needed for the post scanning monitoring period. All the rapid response equipment and resuscitation staff are readily available 24/7 in the intensive care unit setting. All participants will have an existing IV line as they are in the intensive care unit setting.

For each patient subject, the clinically indicated portion of the ultrasound examination will always be performed prior to the research portion of examination. For neonates/infants undergoing hypothermia therapy, CEUS scan will be performed initially after the rewarming period and again one week following the first CEUS scan. It is part of standard of care to obtain initial and follow up brain US for screening and monitoring of suspected hypoxic ischemic injury. For neonates/infants not undergoing hypothermia therapy, first CEUS scan will be performed at the time of injury and one week following injury. Patient charts will be reviewed for history and diagnosis.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 50 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Diagnostic
Official Title: Improved Diagnosis and Prognostication of Hypoxic Ischemic Injury in Neonates and Infants Using Contrast-Enhanced Ultrasound
Actual Study Start Date : February 4, 2019
Estimated Primary Completion Date : July 2019
Estimated Study Completion Date : July 2020

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Ultrasound

Arm Intervention/treatment
Experimental: Contrast-enhanced Ultrasonography
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 may 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 30 minute monitoring period after the first and second injection (if there are two injections of contrast) of the contrast agent.
Drug: Sulfur hexafluoride lipid-type A microspheres
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.

Primary Outcome Measures :
  1. Qualitative and quantitative assessment of CEUS evaluation of brain perfusion [ Time Frame: 2 years ]
    Specific analysis plan consists of both qualitative and quantitative assessment in which description of focal perfusion deficit or lesion, for instance, is reported in correlation with clinical information. Perfusion abnormalities will be qualitatively evaluated (absent - 0, mild hypoperfusion - 1, normal - 2, hyperperfusion - 3) and quantitatively (region of interest placed on brain regions for acquisition of wash-in curves using Matlab software).

Information from the National Library of Medicine

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Ages Eligible for Study:   up to 1 Year   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Neonates and infants with open fontanelles with known or suspected hypoxic injury scheduled for standard of care cranial ultrasound
  • Subjects with post menstrual age (gestational age + chronologic age) to be 36 weeks or older for the subjects being studied
  • Stable clinical condition
  • Subjects not currently on the hypothermia protocol or about to start the hypothermia protocol

Exclusion Criteria:

  • History of hypersensitivity reactions to sulfur hexafluoride lipid microsphere components or to any of the inactive ingredients in LUMASON. Inactive ingredients include 1,2-Dipalmitoyl-sn-glycero-3-phosphoglycerol, sodium salt (DPPG), a minor (1-2%) component normally present in most cell membranes, Diasteroylphosphatidylcholine (DSPC), a commonly used synthetic phospholipids, and palmitic acid, the most commonly found fatty acid in animals.
  • Patient subjects in unstable clinical condition.
  • Subjects on or just about to start hypothermia protocol.
  • Subjects with cardiac shunts or pulmonary insufficiency
  • Subjects who are intubated and on pressors

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT03549520

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United States, Pennsylvania
The Children's Hospital of Philadelphia Recruiting
Philadelphia, Pennsylvania, United States, 19104
Contact: Misun Hwang, MD    267-425-7110   
Contact: Sandra Saade, MD    2674257139   
Principal Investigator: Misun Hwang, MD         
Sponsors and Collaborators
Children's Hospital of Philadelphia

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Responsible Party: Misun Hwang, MD, Sponsor Investigator, Children's Hospital of Philadelphia Identifier: NCT03549520     History of Changes
Other Study ID Numbers: IRB 18-014912
First Posted: June 8, 2018    Key Record Dates
Last Update Posted: March 8, 2019
Last Verified: March 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Misun Hwang, MD, Children's Hospital of Philadelphia:

Additional relevant MeSH terms:
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Brain Diseases
Brain Ischemia
Hypoxia-Ischemia, Brain
Pathologic Processes
Signs and Symptoms, Respiratory
Signs and Symptoms
Central Nervous System Diseases
Nervous System Diseases
Cerebrovascular Disorders
Vascular Diseases
Cardiovascular Diseases
Hypoxia, Brain