Clinical Applications of Contrast-Enhanced Ultrasonography in Pediatric Population - Intravesicle Administration

In children, specifically the intravesicle administration to study vesicoureteral reflux in children already catheterized and scheduled for voiding cystourethrogram (VCUG). Contrast-enhanced ultrasonography is a tremendous advancement from conventional B-mode and color Doppler ultrasonography, as it permits noninvasive, non-ionizing delineation of physiology and pathophysiology with higher resolution and accuracy in children. The technique is particularly useful in pediatric population whose lifetime risk of cancer significantly increases with higher frequency of ionizing radiation. Voiding cystourethrogram is a fluoroscopy technique that can study reflux real time but at the risk of radiation side effects. In this regard, intravesicle administration of ultrasound contrast agent can help avoid radiation in children and potentially replace the conventionally used voiding cystourethrogram.

Study Overview

• Status: Withdrawn
• Conditions: Vesico-Ureteral Reflux
• Intervention / Treatment: Other: Contrast Ultrasound

Detailed Description

The most commonly used genitourinary application of ultrasound contrast agent is for the diagnosis of vesicoureteral reflux via intra-vesicle administration of contrast agent. The utility of ultrasound contrast agent in contrast-enhanced voiding urosonography is well established and published over two decades (Darge 2002, Darge 2008, Darge 2010). As with other applications of ultrasound contrast agents, the method offers the advantages of no radiation, low cost, excellent anatomic detail, and higher sensitivity for reflux detection than VCUG. The most comprehensive study to detail the safety profile of intravesicle ultrasound contrast is by Papadopoulou et al. (Papadopoulou, Ntoulia et al. 2014) which described a total of 1,010 children (563 girls, 447 boys) with a mean age of 2.9 years. No adverse events were reported at 1 hour after exam. Follow-up phone interviews revealed no adverse events in the majority (973 of 1,010). The remaining 37 children experienced mild symptoms including dysuria (n=26) and urinary retention (n=2) which may have been related to catheterization rather than the contrast agent. A recent European survey at 29 centers evaluating the use of ultrasound contrast agent in 4,131 children for pediatric reflux diagnosis reported no adverse events (Riccabona 2012).

The procedure consists of pre-contrast, post-contrast, voiding phase, and post-void depiction of the kidneys, ureters, bladder, and transperineal scan of the urethra, for identification of potential ectopic ureters (Darge 2008, Duran, del Riego et al. 2012) that can easily be missed on non-distended ureters on CT, MRI, or radionuclide imaging. The two primary methods of contrast injection includes direct injection into a partially filled bladder (Darge 2008) and another using a saline bag for subsequent drip infusion via the catheter into the bladder (Back, Edgar et al. 2015).

• Study Type: Interventional
• Phase: Not Applicable

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: No older than 18 years (Child, Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Male or female patients aged 0-17 years undergoing an ultrasound for a clinical indication at the Johns Hopkins Hospital
• Willing to either extend a previously scheduled clinically indicated voiding cystourethrogram

Exclusion Criteria:

• Known or suspected right-to-left, bi-directional, or transient right-to-left cardiac shunts
• 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.

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
Other: Contrast Ultrasound; Patients with vesicoureteral reflux will receive contrast ultrasound via Foley catheter for study of vesicoureteral reflux.	Other: Contrast Ultrasound; For diagnostic purposes, intravesicle administration of contrast ultrasound agent will be performed to study vesicoureteral reflux.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Clinical Applications of Contrast-Enhanced Ultrasonography in Pediatric Population - Intravesicle Administration	The presence of vesicoureteral reflux is assessed as the primary outcome measure. Qualitative evaluation is performed to assess the presence of contrast within the collecting systems, which then correlates with vesicoureteral reflux. Since this is a qualitative evaluation based on the acquired radiologic images, there is no unit, but the degree of vesicoureteral reflux is assessed. Vesicoureteral reflux is graded into I to V grades based on the severity.	10 years

Collaborators and Investigators

• Sponsor: Johns Hopkins University

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2017
• Primary Completion (Actual): January 9, 2018
• Study Completion (Actual): January 9, 2018

Study Registration Dates

• First Submitted: December 5, 2016
• First Submitted That Met QC Criteria: December 7, 2016
• First Posted (Estimate): December 8, 2016

Study Record Updates

• Last Update Posted (Actual): January 25, 2018
• Last Update Submitted That Met QC Criteria: January 22, 2018
• Last Verified: January 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Urologic Diseases; Urinary Bladder Diseases; Vesico-Ureteral Reflux
• Other Study ID Numbers: 00118038

Plan for Individual participant data (IPD)

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