CEUS Evaluation of Bowel Perfusion in Necrotizing Enterocolitis

Phase 3

Terminated

Conditions: Bowel Ischemic
Necrotizing Enterocolitis of Newborn

Interventions: Drug: Sulfur hexafluoride lipid-type A microspheres

Registration Number: NCT03549507

Lead Sponsor: Children's Hospital of Philadelphia

Brief 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. 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.

Recruitment & Eligibility

Status: TERMINATED

Sex: All

Target Recruitment: 1

Inclusion Criteria

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

Exclusion Criteria

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Contrast-enhanced Ultrasonography	Sulfur hexafluoride lipid-type A microspheres	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.

Primary Outcome Measures

Name	Time	Method
Early Detection of Altered Bowel Perfusion Using CEUS	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

Secondary Outcome Measures

Name	Time	Method
Number of Participants With Completed CEUS Exams, Categorized by Diagnostic-Quality Scoring System	2 years	Scoring system of non-diagnostic (1), moderate artifacts degrading diagnostic quality (2), mild artifacts without degradation of diagnostic quality (3), and diagnostic (4).