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CeVUS With Intravesical Administration of OPTISON TM (Trademark) in Children (ceVUS)

Primary Purpose

Vesico-Ureteral Reflux

Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
OPTISON
Sponsored by
Kassa Darge
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional diagnostic trial for Vesico-Ureteral Reflux focused on measuring Ultrasound, Ultrasound Contrast Agents, Optison, contrast enhanced Voiding Urosonography (ceVUS), ceVUS, Vesicoureteral Reflux, Children, Kidney, Bladder, Urethra, Voiding Cystourethrography (VCUG), VCUG, Safety, Urinary tract

Eligibility Criteria

undefined - 18 Years (Child, Adult)All SexesDoes not accept healthy volunteers

Inclusion criteria:

  1. Children 2-18 years (first age cohort).
  2. Children 0-18 years (second age cohort).
  3. Referred to the Children's Hospital of Philadelphia (CHOP) for the performance of the clinically indicated Voiding Cystourethrography (VCUG) examination.
  4. Parental/guardian permission (informed consent) and if appropriate, child's assent for additional performance of contrast enhanced Voiding Urosonography (ceVUS) examination.

Exclusion criteria:

  1. Hypersensitivity to perflutren, blood, blood products or albumin.
  2. Children requiring sedation for VCUG or ceVUS examinations.
  3. Parents/guardians or subjects who, in the opinion of the principal investigator, may be non-compliant with study schedules or procedures.

Sites / Locations

  • Department of Radiology, the Children's Hospital of Philadelphia

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Comparative performance of ceVUS & VCUG

Arm Description

Contrast enhanced Voiding Urosonography (ceVUS) will be performed with the intravesical administration of 0.1%-0.5% OPTISON / normal saline solution. The exact OPTISON dose (ml) that will be adjusted according to the age-related bladder filling capacity with a dose (ml) range from 0.3 mL in newborns to 3 mL in 18 year-old children. Voiding Cystourethrography (VCUG) exam will be subsequently performed using the same bladder catheter with intravesical administration of the x-ray contrast agent.

Outcomes

Primary Outcome Measures

Number of Pelvic-ureter-units (PUUs) Detected With Vesicoureteral Reflux by Contrast Enhanced Voiding Urosonography (ceVUS) and by Voiding Cystourethrography (VCUG).
Presence or absence of vesicoureteral reflux identified by ceVUS and VCUG in each pelvic-ureter-unit (PUU) of each participant. PUU is an anatomic term that is used to describe the part of the urinary tract consisting of the renal calyces, pelvis and ureter. Grading the severity of reflux detected by ceVUS and VCUG. Grade 0: absence of reflux. If reflux is present, a 5 grade scale (grades I-V) is used to evaluate its severity. Grade I: reflux in the ureter, grade II: reflux up to the renal pelvis, grade III: reflux up to the renal pelvis with mild dilation of the ureter and pelvicalyceal system, grade IV reflux up to the renal pelvis with moderate dilation but preserved papillary impressions, grade V: reflux up to the renal pelvis with severe dilation and loss of papillary impressions. Higher grades of reflux are associated with increased risk of urinary tract infection. Imaging of the urethra during voiding (urethra visualized or not) and urethra pathology detection.
Number of Participants With Adverse Events Following Contrast Enhanced Voiding Urosonography (ceVUS) With OPTISON and Voiding Cystourethrography (VCUG).
The overall safety and tolerability of ceVUS with OPTISON was assessed before, during and immediately after each ceVUS and VCUG examinations, and in follow-up telephone interviews. Assessments included: evaluation of body systems for signs of generalized hypersensitivity, allergic or anaphylactoid reactions monitoring of heart rate and pulse oxygen saturation telephone questionnaire-based interview of parents/guardians and children 48 hours after the examinations for delayed adverse events. The severity of any possible adverse event was classified as mild, moderate or serious and the onset of symptoms was categorized as acute, subacute or delayed according to the World Health Organization (WHO) classifications. In addition, the adverse event was classified as anticipated if it was expected given the study related procedures or unanticipated if the subject was exposed to greater risk than previously known or recognized.

Secondary Outcome Measures

Compare the Diagnostic Accuracy of Contrast Enhanced Voiding Urosonography (ceVUS) With Voiding CystoUrethroGraphy (VCUG) for Vesicoureteral Reflux Detection and Urethral Imaging in Children.
The diagnostic accuracy of ceVUS will be assessed by evaluation of the true positive, true negative, false positive and false negative cases of reflux and urethral imaging findings detected by ceVUS and VCUG examinations.

Full Information

First Posted
June 25, 2014
Last Updated
October 29, 2018
Sponsor
Kassa Darge
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1. Study Identification

Unique Protocol Identification Number
NCT02204917
Brief Title
CeVUS With Intravesical Administration of OPTISON TM (Trademark) in Children
Acronym
ceVUS
Official Title
Contrast Enhanced Voiding Urosonography (ceVUS) With the Intravesical Administration of the Ultrasound Contrast Agent OPTISON TM (Trademark) for Vesicoureteral Reflux Detection and Urethral Imaging in Children.
Study Type
Interventional

2. Study Status

Record Verification Date
October 2018
Overall Recruitment Status
Completed
Study Start Date
July 2014 (undefined)
Primary Completion Date
March 2016 (Actual)
Study Completion Date
March 2017 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
Kassa Darge

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
In this clinical trial the investigators aim to evaluate the diagnostic feasibility and safety of ceVUS with the intravesical use of OPTISON for vesicoureteral reflux detection and urethral imaging in children.
Detailed Description
Contrast enhanced Voiding Urosonography (ceVUS) is a radiation free, highly sensitive imaging modality for vesicoureteral reflux (VUR) and urethral imaging in children. It employs ultrasound technology in combination with ultrasound contrast agent, which is administered intravesically via a bladder catheter. Currently, second generation ultrasound contrast agents are commercially available, comprising of gas-filled microbubbles. CeVUS in children is being widely practiced, primarily in Europe, despite the fact that none of the commercially available ultrasound contrast agents are yet approved for clinical applications in pediatric population. In the United States, there is limited clinical experience with ceVUS in children. Among the currently commercially available ultrasound contrast agents, OPTISON has already been used in research and off-label in clinical settings involving adults and children. One in-vitro study has been conducted aiming to optimize the ultrasound technical parameters and the dose of OPTISON for intravesical administration in children. In this clinical trial the investigators aim to evaluate the diagnostic feasibility and safety of ceVUS with the intravesical use of OPTISON for vesicoureteral reflux detection and urethral imaging in children.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Vesico-Ureteral Reflux
Keywords
Ultrasound, Ultrasound Contrast Agents, Optison, contrast enhanced Voiding Urosonography (ceVUS), ceVUS, Vesicoureteral Reflux, Children, Kidney, Bladder, Urethra, Voiding Cystourethrography (VCUG), VCUG, Safety, Urinary tract

7. Study Design

Primary Purpose
Diagnostic
Study Phase
Phase 1, Phase 2
Interventional Study Model
Single Group Assignment
Model Description
Comparative performance of contrast enhanced Voiding Urosonography (ceVUS) and Voiding Cystourethrography (VCUG) in the same participant and in the same session.
Masking
None (Open Label)
Allocation
N/A
Enrollment
31 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Comparative performance of ceVUS & VCUG
Arm Type
Experimental
Arm Description
Contrast enhanced Voiding Urosonography (ceVUS) will be performed with the intravesical administration of 0.1%-0.5% OPTISON / normal saline solution. The exact OPTISON dose (ml) that will be adjusted according to the age-related bladder filling capacity with a dose (ml) range from 0.3 mL in newborns to 3 mL in 18 year-old children. Voiding Cystourethrography (VCUG) exam will be subsequently performed using the same bladder catheter with intravesical administration of the x-ray contrast agent.
Intervention Type
Drug
Intervention Name(s)
OPTISON
Other Intervention Name(s)
Perflutren Protein-Type A Microspheres
Intervention Description
Contrast enhanced Voiding Urosonography (ceVUS) with intravesical administration of OPTISON for vesicoureteral reflux detection and urethral imaging in children. Voiding Cystourethrography (VCUG) examination will be subsequently performed as part of the standard care.
Primary Outcome Measure Information:
Title
Number of Pelvic-ureter-units (PUUs) Detected With Vesicoureteral Reflux by Contrast Enhanced Voiding Urosonography (ceVUS) and by Voiding Cystourethrography (VCUG).
Description
Presence or absence of vesicoureteral reflux identified by ceVUS and VCUG in each pelvic-ureter-unit (PUU) of each participant. PUU is an anatomic term that is used to describe the part of the urinary tract consisting of the renal calyces, pelvis and ureter. Grading the severity of reflux detected by ceVUS and VCUG. Grade 0: absence of reflux. If reflux is present, a 5 grade scale (grades I-V) is used to evaluate its severity. Grade I: reflux in the ureter, grade II: reflux up to the renal pelvis, grade III: reflux up to the renal pelvis with mild dilation of the ureter and pelvicalyceal system, grade IV reflux up to the renal pelvis with moderate dilation but preserved papillary impressions, grade V: reflux up to the renal pelvis with severe dilation and loss of papillary impressions. Higher grades of reflux are associated with increased risk of urinary tract infection. Imaging of the urethra during voiding (urethra visualized or not) and urethra pathology detection.
Time Frame
10-15 minutes.
Title
Number of Participants With Adverse Events Following Contrast Enhanced Voiding Urosonography (ceVUS) With OPTISON and Voiding Cystourethrography (VCUG).
Description
The overall safety and tolerability of ceVUS with OPTISON was assessed before, during and immediately after each ceVUS and VCUG examinations, and in follow-up telephone interviews. Assessments included: evaluation of body systems for signs of generalized hypersensitivity, allergic or anaphylactoid reactions monitoring of heart rate and pulse oxygen saturation telephone questionnaire-based interview of parents/guardians and children 48 hours after the examinations for delayed adverse events. The severity of any possible adverse event was classified as mild, moderate or serious and the onset of symptoms was categorized as acute, subacute or delayed according to the World Health Organization (WHO) classifications. In addition, the adverse event was classified as anticipated if it was expected given the study related procedures or unanticipated if the subject was exposed to greater risk than previously known or recognized.
Time Frame
Within 1 hour and up to 2 days after ceVUS and VCUG examinations completion.
Secondary Outcome Measure Information:
Title
Compare the Diagnostic Accuracy of Contrast Enhanced Voiding Urosonography (ceVUS) With Voiding CystoUrethroGraphy (VCUG) for Vesicoureteral Reflux Detection and Urethral Imaging in Children.
Description
The diagnostic accuracy of ceVUS will be assessed by evaluation of the true positive, true negative, false positive and false negative cases of reflux and urethral imaging findings detected by ceVUS and VCUG examinations.
Time Frame
10-15 minutes.

10. Eligibility

Sex
All
Maximum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion criteria: Children 2-18 years (first age cohort). Children 0-18 years (second age cohort). Referred to the Children's Hospital of Philadelphia (CHOP) for the performance of the clinically indicated Voiding Cystourethrography (VCUG) examination. Parental/guardian permission (informed consent) and if appropriate, child's assent for additional performance of contrast enhanced Voiding Urosonography (ceVUS) examination. Exclusion criteria: Hypersensitivity to perflutren, blood, blood products or albumin. Children requiring sedation for VCUG or ceVUS examinations. Parents/guardians or subjects who, in the opinion of the principal investigator, may be non-compliant with study schedules or procedures.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Kassa Darge, MD, PhD
Organizational Affiliation
Department of Radiology, the Children's Hospital of Philadelphia
Official's Role
Principal Investigator
Facility Information:
Facility Name
Department of Radiology, the Children's Hospital of Philadelphia
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19104
Country
United States

12. IPD Sharing Statement

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CeVUS With Intravesical Administration of OPTISON TM (Trademark) in Children

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