Necrotizing Enterocolitis of NewbornPhase 3NCT03549507
CEUS Evaluation of Bowel Perfusion in Necrotizing Enterocolitis
A Phase 3 study testing Sulfur hexafluoride lipid-type A microspheres in people with Necrotizing Enterocolitis of Newborn and Bowel Ischemic, run by Children's Hospital of Philadelphia at 1 site in United States.
Trial summary
There is no bedside imaging technique that can quantify dynamic bowel perfusion with high soft tissue contrast and sensitivity in necrotizing enterocolitis (NEC). Our goal is to assess the feasibility of utilizing contrast-enhanced ultrasound (CEUS) in bedside monitoring of bowel perfusion in NEC. Read more about this study
- Who is it for?
- Ages 0 years to 18 months
- Conditions the study is for
- Necrotizing Enterocolitis of Newborn, Bowel Ischemic
- 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
- 4 Nov 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 0 years to 18 months
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- Males and females aged 1.5 years or younger
- Post menstrual age of 29 weeks or older
- Patients with suspected or diagnosed necrotizing enterocolitis
- 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 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: Evaluation of Bowel Perfusion With Contrast-Enhanced Ultrasound in Necrotizing Enterocolitis
There is no bedside imaging technique that can quantify dynamic bowel perfusion with high soft tissue contrast and sensitivity in necrotizing enterocolitis (NEC). Our goal is to assess the feasibility of utilizing contrast-enhanced ultrasound (CEUS) in bedside monitoring of bowel perfusion in NEC. Patients with suspected or diagnosed NEC will be recruited for the study. Following parental consent, the subject will undergo CEUS, performed separately from any clinically indicated conventional US, in the ICU. Subjects will be scanned with CEUS at two different time-points (at the time NEC is first suspected or diagnosed and at time of MRI scan). The CEUS scans 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
Early detection of ischemia and necrotic bowel which leads to perforation is vital in improving morbidity and mortality associated with NEC. Abdominal radiography, the standard imaging algorithm for monitoring of NEC, has a low sensitivity of 40% in the diagnosis of severe NEC with necrotic bowel. There is a dire need to introduce better imaging tools such as CEUS to the clinical setting that can detect NEC at an early stage and prompt therapeutic implementation. CEUS enables safe, serial monitoring of dynamic quantification of bowel perfusion at the bedside.
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 of suspected or diagnosed NEC, and at the time of surgery (for subjects undergoing surgery as part of clinical care) or at short-term follow-up of clinical condition (approximately 1 week after the first scan) for a total of two CEUS exams of 1 hour and 15-minute duration each.
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 bowel 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
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. Two bolus injections will be performed to evaluate for dynamic bowel perfusion and several 2-minute cine clips as well as static images will be acquired during the exam.
| 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 (if there are two injections of contrast) 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.
Early Detection of Altered Bowel Perfusion Using CEUS
Comparison of bowel perfusion between normal subjects (those with suspected or at risk of necrotizing enterocolitis but turn out to be normal on imaging and clinical evaluation) versus NEC patients
Measured: 2 years
Secondary outcomes (1)
Number of Participants With Completed 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: 2 years
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 start4 Nov 2020
- Primary completion7 May 2024
- Study completion7 May 2024
Why it stopped: Lack of enrollment.
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 Necrotizing Enterocolitis of NewbornStudies 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
- Investigators
- Misun Hwang, MD, Principal investigator, Children's Hospital of Philadelphia
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03549507
- Sponsor's protocol ID
- 18-014910
- Status last verified
- Oct 2024
- First submitted
- 25 May 2018
- Last updated
- 12 Nov 2024
- 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 12 Nov 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Evaluation of Bowel Perfusion With Contrast-Enhanced Ultrasound in Necrotizing Enterocolitis
- ClinicalTrials.gov ID
- NCT03549507
- Acronym / sponsor ID
- 18-014910
- Keywords
- Ultrasound, Contrast-enhanced ultrasound
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Lack of enrollment.
- Enrolment
- 1 participants (actual)
- Lead sponsor
- Children's Hospital of PhiladelphiaUniversity, hospital or other
- Collaborators
- Bracco Diagnostics, Inc
- Study start
- 4 Nov 2020 (actual)
- Primary completion
- 7 May 2024 (actual)
- Study completion
- 7 May 2024 (actual)
- First posted
- 8 Jun 2018 (actual)
- Results
- Posted 12 Nov 2024
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
There is no bedside imaging technique that can quantify dynamic bowel perfusion with high soft tissue contrast and sensitivity in necrotizing enterocolitis (NEC). Our goal is to assess the feasibility of utilizing contrast-enhanced ultrasound (CEUS) in bedside monitoring of bowel perfusion in NEC. Patients with suspected or diagnosed NEC will be recruited for the study. Following parental consent, the subject will undergo CEUS, performed separately from any clinically indicated conventional US, in the ICU. Subjects will be scanned with CEUS at two different time-points (at the time NEC is first suspected or diagnosed and at time of MRI scan). The CEUS scans 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
Early detection of ischemia and necrotic bowel which leads to perforation is vital in improving morbidity and mortality associated with NEC. Abdominal radiography, the standard imaging algorithm for monitoring of NEC, has a low sensitivity of 40% in the diagnosis of severe NEC with necrotic bowel. There is a dire need to introduce better imaging tools such as CEUS to the clinical setting that can detect NEC at an early stage and prompt therapeutic implementation. CEUS enables safe, serial monitoring of dynamic quantification of bowel perfusion at the bedside.
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 of suspected or diagnosed NEC, and at the time of surgery (for subjects undergoing surgery as part of clinical care) or at short-term follow-up of clinical condition (approximately 1 week after the first scan) for a total of two CEUS exams of 1 hour and 15-minute duration each.
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 bowel 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 (if there are two injections of contrast) of the contrast agent. |
Who may qualify
- Ages
- 0 years to 18 months
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (5 listed)
- Males and females aged 1.5 years or younger
- Post menstrual age of 29 weeks or older
- Patients with suspected or diagnosed necrotizing enterocolitis
- 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 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. Two bolus injections will be performed to evaluate for dynamic bowel perfusion and several 2-minute cine clips as well as static images will be acquired during the exam. | Drug | Contrast-enhanced Ultrasonography |
Primary outcome
Early Detection of Altered Bowel Perfusion Using CEUS
Time frame: 2 years
Comparison of bowel perfusion between normal subjects (those with suspected or at risk of necrotizing enterocolitis but turn out to be normal on imaging and clinical evaluation) versus NEC patients
1 secondary outcome
Number of Participants With Completed CEUS Exams, Categorized by Diagnostic-Quality Scoring System
Time frame: 2 years
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Nov 2024.
- 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 Necrotizing Enterocolitis of Newborn
RecruitingObservational study
Multidimensional Dynamic Early Warning System for Neonatal Necrotizing Enterocolitis: A Multicenter Clinical Study
NEC - Necrotizing Enterocolitis
Recruiting
Fecal Microbiota Transplantation (FMT) as a Prophylaxis of Necrotizing Enterocolitis (NEC) - Clinical Study
Necrotizing Enterocolitis (NEC), Necrotizing Enterocolitis of Newborn
Active, not recruitingObservational study
Early Predictors of Necrotizing Enterocolitis in Neonates
Necrotizing Enterocolitis
RecruitingObservational study
The Correlation Between Red Cell Transfusion and Complications of Prematurity
Retinopathy of Prematurity (ROP), Bronchopulmonary Dysplasia (BPD)
Recruiting
A Feasibility Study to Evaluate Safety and Probable Benefit of the Eclipse XL1 System for Distraction Enterogenesis in Adult and Pediatric Patients With Short Bowel Syndrome
Short Bowel Syndrome
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.
Misun Hwang, MD principal investigator
Children's Hospital of Philadelphia
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 Necrotizing Enterocolitis of Newborn and Bowel Ischemic, 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 5 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: stopped early, as of the sponsor's last update on 12 Nov 2024. 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 12 Nov 2024). 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?
Early Detection of Altered Bowel Perfusion Using CEUS (time frame: 2 years). 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 NCT03549507, 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 12 Nov 2024.