Trial Outcomes & Findings for CeVUS With Intravesical Administration of OPTISON TM (Trademark) in Children (NCT NCT02204917)

NCT ID: NCT02204917

Last Updated: 2018-11-27

Results Overview

1. 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. 2. 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. 3. Imaging of the urethra during voiding (urethra visualized or not) and urethra pathology detection.

Recruitment status

COMPLETED

Study phase

PHASE1/PHASE2

Target enrollment

31 participants

Primary outcome timeframe

10-15 minutes.

Results posted on

2018-11-27

Participant Flow

From September 2014 to April 2015, the study team recruited and enrolled 31 eligible subjects scheduled for the clinically indicated voiding cysteourethrography (VCUG) examination from the daily inpatients/outpatients program of the Radiology Department at the Children's Hospital of Philadelphia.

One subject was enrolled into the study (informed consent signed), however, sedation was required as standard of care to perform the clinically indicated VCUG examination. Sedation constitutes an exclusion criterion. Therefore, this subject although enrolled into the study, did not actually complete it.

Participant milestones

Participant milestones
Measure
ceVUS With the Use of OPTISON & VCUG in the Same Session
OPTISON will be resuspended just before the performance of ceVUS examination, and 0.1%-0.5% of the bladder filling volume OPTISON / normal saline solution will be used for intravesical administration. The exact OPTISON dose (ml) will be adjusted according to the age-related bladder filling capacity with the maximum OPTISON dose (ml) range from 0.3 mL in newborns to 3 mL in 18 year-old children. VCUG exam will be performed using the same bladder catheter with intravesical administration of the x-ray contrast agent.
Overall Study
STARTED
31
Overall Study
COMPLETED
30
Overall Study
NOT COMPLETED
1

Reasons for withdrawal

Reasons for withdrawal
Measure
ceVUS With the Use of OPTISON & VCUG in the Same Session
OPTISON will be resuspended just before the performance of ceVUS examination, and 0.1%-0.5% of the bladder filling volume OPTISON / normal saline solution will be used for intravesical administration. The exact OPTISON dose (ml) will be adjusted according to the age-related bladder filling capacity with the maximum OPTISON dose (ml) range from 0.3 mL in newborns to 3 mL in 18 year-old children. VCUG exam will be performed using the same bladder catheter with intravesical administration of the x-ray contrast agent.
Overall Study
Protocol Violation
1

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure
ceVUS With the Use of OPTISON & VCUG in the Same Session
n=30 Participants
OPTISON will be resuspended just before the performance of ceVUS examination, and 01%-0.5% OPTISON solution will be used for intravesical administration. The exact OPTISON dose (ml) will be adjusted according to the age-related bladder filling capacity with a maximum dose (ml) range from 0.3 mL in newborns to 3 mL in 18 year-old children. VCUG exam will be performed as part of the standard care using the same bladder catheter with intravesical administration of the x-ray contrast agent.
Age, Categorical
<=18 years
30 Participants
n=5 Participants
Age, Categorical
Between 18 and 65 years
0 Participants
n=5 Participants
Age, Categorical
>=65 years
0 Participants
n=5 Participants
Sex: Female, Male
Female
21 Participants
n=5 Participants
Sex: Female, Male
Male
9 Participants
n=5 Participants
Ethnicity (NIH/OMB)
Hispanic or Latino
3 Participants
n=5 Participants
Ethnicity (NIH/OMB)
Not Hispanic or Latino
27 Participants
n=5 Participants
Ethnicity (NIH/OMB)
Unknown or Not Reported
0 Participants
n=5 Participants
Race (NIH/OMB)
American Indian or Alaska Native
0 Participants
n=5 Participants
Race (NIH/OMB)
Asian
2 Participants
n=5 Participants
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
0 Participants
n=5 Participants
Race (NIH/OMB)
Black or African American
5 Participants
n=5 Participants
Race (NIH/OMB)
White
17 Participants
n=5 Participants
Race (NIH/OMB)
More than one race
6 Participants
n=5 Participants
Race (NIH/OMB)
Unknown or Not Reported
0 Participants
n=5 Participants
Region of Enrollment
United States
30 Participants
n=5 Participants

PRIMARY outcome

Timeframe: 10-15 minutes.

Population: In total, 59 kidneys with 62 pelvic-ureteric units (PUUs) in 30 children were analyzed.

1. 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. 2. 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. 3. Imaging of the urethra during voiding (urethra visualized or not) and urethra pathology detection.

Outcome measures

Outcome measures
Measure
Severity of Reflux With ceVUS
n=62 Number of Pelvic-Ureteric-Units (PUUs)
Contrast enhanced Voiding Urosonography (ceVUS) OPTISON will be performed with the intravesical administration of 0.1%-0.5% OPTISON/normal saline solution. The exact OPTISON dose (ml) will be adjusted according to the age-related bladder filling capacity with a maximum dose (ml) range from 0.3 mL in newborns to 3 mL in 18 year-old children.
Severity of Reflux With VCUG
n=62 Number of Pelvic-Ureteric-Units (PUUs)
Voiding Cystourethrography (VCUG) exam will be performed after ceVUS using the same bladder catheter with intravesical administration of the x-ray contrast agent.
Number of Pelvic-ureter-units (PUUs) Detected With Vesicoureteral Reflux by Contrast Enhanced Voiding Urosonography (ceVUS) and by Voiding Cystourethrography (VCUG).
Grade 0 reflux
50 pelvic-ureteric units (PUUs)
50 pelvic-ureteric units (PUUs)
Number of Pelvic-ureter-units (PUUs) Detected With Vesicoureteral Reflux by Contrast Enhanced Voiding Urosonography (ceVUS) and by Voiding Cystourethrography (VCUG).
Grade I reflux
2 pelvic-ureteric units (PUUs)
2 pelvic-ureteric units (PUUs)
Number of Pelvic-ureter-units (PUUs) Detected With Vesicoureteral Reflux by Contrast Enhanced Voiding Urosonography (ceVUS) and by Voiding Cystourethrography (VCUG).
Grade II reflux
8 pelvic-ureteric units (PUUs)
6 pelvic-ureteric units (PUUs)
Number of Pelvic-ureter-units (PUUs) Detected With Vesicoureteral Reflux by Contrast Enhanced Voiding Urosonography (ceVUS) and by Voiding Cystourethrography (VCUG).
Grade III reflux
2 pelvic-ureteric units (PUUs)
4 pelvic-ureteric units (PUUs)
Number of Pelvic-ureter-units (PUUs) Detected With Vesicoureteral Reflux by Contrast Enhanced Voiding Urosonography (ceVUS) and by Voiding Cystourethrography (VCUG).
Grade IV reflux
0 pelvic-ureteric units (PUUs)
0 pelvic-ureteric units (PUUs)
Number of Pelvic-ureter-units (PUUs) Detected With Vesicoureteral Reflux by Contrast Enhanced Voiding Urosonography (ceVUS) and by Voiding Cystourethrography (VCUG).
Grade V reflux
0 pelvic-ureteric units (PUUs)
0 pelvic-ureteric units (PUUs)

PRIMARY outcome

Timeframe: Within 1 hour and up to 2 days after ceVUS and VCUG examinations completion.

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: 1. evaluation of body systems for signs of generalized hypersensitivity, allergic or anaphylactoid reactions 2. monitoring of heart rate and pulse oxygen saturation 3. 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.

Outcome measures

Outcome measures
Measure
Severity of Reflux With ceVUS
n=30 Participants
Contrast enhanced Voiding Urosonography (ceVUS) OPTISON will be performed with the intravesical administration of 0.1%-0.5% OPTISON/normal saline solution. The exact OPTISON dose (ml) will be adjusted according to the age-related bladder filling capacity with a maximum dose (ml) range from 0.3 mL in newborns to 3 mL in 18 year-old children.
Severity of Reflux With VCUG
Voiding Cystourethrography (VCUG) exam will be performed after ceVUS using the same bladder catheter with intravesical administration of the x-ray contrast agent.
Number of Participants With Adverse Events Following Contrast Enhanced Voiding Urosonography (ceVUS) With OPTISON and Voiding Cystourethrography (VCUG).
Number of Participants without Adverse Events
29 participants
Number of Participants With Adverse Events Following Contrast Enhanced Voiding Urosonography (ceVUS) With OPTISON and Voiding Cystourethrography (VCUG).
Number of Participants with Adverse Events
1 participants

SECONDARY outcome

Timeframe: 10-15 minutes.

Population: Voiding Cysteourethrography (VCUG) is used as the reference standard the results for ceVUS.

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.

Outcome measures

Outcome measures
Measure
Severity of Reflux With ceVUS
n=30 Participants
Contrast enhanced Voiding Urosonography (ceVUS) OPTISON will be performed with the intravesical administration of 0.1%-0.5% OPTISON/normal saline solution. The exact OPTISON dose (ml) will be adjusted according to the age-related bladder filling capacity with a maximum dose (ml) range from 0.3 mL in newborns to 3 mL in 18 year-old children.
Severity of Reflux With VCUG
Voiding Cystourethrography (VCUG) exam will be performed after ceVUS using the same bladder catheter with intravesical administration of the x-ray contrast agent.
Compare the Diagnostic Accuracy of Contrast Enhanced Voiding Urosonography (ceVUS) With Voiding CystoUrethroGraphy (VCUG) for Vesicoureteral Reflux Detection and Urethral Imaging in Children.
sensitivity
91.7 percentage
Interval 61.5 to 99.8
Compare the Diagnostic Accuracy of Contrast Enhanced Voiding Urosonography (ceVUS) With Voiding CystoUrethroGraphy (VCUG) for Vesicoureteral Reflux Detection and Urethral Imaging in Children.
specificity
98.0 percentage
Interval 89.4 to 99.9
Compare the Diagnostic Accuracy of Contrast Enhanced Voiding Urosonography (ceVUS) With Voiding CystoUrethroGraphy (VCUG) for Vesicoureteral Reflux Detection and Urethral Imaging in Children.
positive predictive value
91.7 percentage
Interval 61.1 to 98.7
Compare the Diagnostic Accuracy of Contrast Enhanced Voiding Urosonography (ceVUS) With Voiding CystoUrethroGraphy (VCUG) for Vesicoureteral Reflux Detection and Urethral Imaging in Children.
negative predictive value
98.0 percentage
Interval 88.2 to 99.7

Adverse Events

ceVUS With the Use of OPTISON & VCUG in the Same Session

Serious events: 0 serious events
Other events: 1 other events
Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure
ceVUS With the Use of OPTISON & VCUG in the Same Session
n=30 participants at risk
OPTISON will be resuspended just before the performance of ceVUS examination, and 0.1%-0.5% of the bladder filling volume OPTISON / normal saline solution will be used for intravesical administration. The exact OPTISON dose (ml) will be adjusted according to the age-related bladder filling capacity with the maximum OPTISON dose (ml) range from 0.3 mL in newborns to 3 mL in 18 year-old children. VCUG exam will be performed using the same bladder catheter with intravesical administration of the x-ray contrast agent.
Renal and urinary disorders
Dysuria
3.3%
1/30 • Number of events 1 • During 48 hours following the study participation

Additional Information

Dr. Kassa Darge, MD, PhD, Radiologist-in-Chief

Children's Hospital of Philadelphia

Phone: 267-425-7110

Results disclosure agreements

  • Principal investigator is a sponsor employee
  • Publication restrictions are in place