CEUS Evaluation of Bowel Perfusion in Necrotizing Enterocolitis

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.

Study Overview

• Status: Recruiting
• Conditions: Necrotizing Enterocolitis of Newborn; Bowel Ischemic
• Intervention / Treatment: Drug: Sulfur hexafluoride lipid-type A microspheres

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 Type: Interventional
• Enrollment (Estimated): 200
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Misun Hwang, MD; Phone Number: 267-425-7129; Email: hwangm@chop.edu
• Study Contact Backup: Name: Santiago Martinez-correa, MD; Phone Number: 2674257139; Email: martinezcs@chop.edu

Study Locations

• United States
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Recruiting
      • The Children's Hospital of Philadelphia
      • Principal Investigator: Misun Hwang, MD
      • Contact: Misun Hwang, MD; Phone Number: 267-425-7110; Email: hwangm@chop.edu
      • Contact: Santiago Martinez, MD; Phone Number: 2674257139; Email: martinezcs@chop.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 second to 1 year (Child)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Males and females aged 1.5 years or younger
2. Post menstrual age of 29 weeks or older
3. Patients with suspected or diagnosed necrotizing enterocolitis
4. Patient in the Children's Hospital of Philadelphia (CHOP) neonatal intensive care unit (NICU) or pediatric intensive care unit (PICU)
5. Parental permission

Exclusion Criteria:

1. Medical history of Lumason hypersensitivity
2. 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
3. Pulmonary insufficiency as defined by FiO2 requirements of >40% and/or subjects with pulmonary hypertension requiring nitric oxide

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / 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 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.

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. 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
CEUS technique use to detect early alterations in bowel perfusion in Necrotizing Enterocolitis (NEC)	The differences in 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 will be assessed qualitatively and quantitatively.	2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Diagnostic quality of the CEUS exams	Diagnostic quality of the CEUS exams will be evaluated with the scoring system of non-diagnostic (1), moderate artifacts degrading diagnostic quality (2), mild artifacts without degradation of diagnostic quality (3), and diagnostic (4).	2 years

Collaborators and Investigators

• Sponsor: Children's Hospital of Philadelphia
• Collaborators: Bracco Diagnostics, Inc
• Investigators: Principal Investigator: Misun Hwang, MD, Children's Hospital of Philadelphia

Publications and helpful links

General 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.

Study record dates

Study Major Dates

• Study Start (Actual): November 4, 2020
• Primary Completion (Estimated): June 12, 2024
• Study Completion (Estimated): June 12, 2024

Study Registration Dates

• First Submitted: May 25, 2018
• First Submitted That Met QC Criteria: May 25, 2018
• First Posted (Actual): June 8, 2018

Study Record Updates

• Last Update Posted (Estimated): January 19, 2024
• Last Update Submitted That Met QC Criteria: January 18, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Keywords: Ultrasound; Contrast-enhanced ultrasound
• Additional Relevant MeSH Terms: Digestive System Diseases; Gastrointestinal Diseases; Gastroenteritis; Intestinal Diseases; Enterocolitis; Enterocolitis, Necrotizing
• Other Study ID Numbers: 18-014910

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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