Vesico-Ureteral RefluxPhase 1/2ceVUSNCT02204917
CeVUS With Intravesical Administration of OPTISON TM (Trademark) in Children
A Phase 1/2 study testing OPTISON in people with Vesico-Ureteral Reflux, run by Kassa Darge at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages Up to 18 years
- Conditions the study is for
- Vesico-Ureteral Reflux
- What is being tested?
- OPTISON
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 31 participants
- Where
- 1 siteUnited States
- Study dates
- Jul 2014to Mar 2017
- Phase
- Phase 1/2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Up to 18 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- 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.
Who cannot join
- 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.
Trial locations and contacts
1 site in 1 country.
United States1 site
Department of Radiology, the Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, 19104
About this study
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.
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.
Read the 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.
- Conditions
- Vesico-Ureteral Reflux
- Being tested
- OPTISON
- 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
- Medical subject headings
- Vesico-Ureteral Reflux
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
OPTISONDrug
Also called Perflutren Protein-Type A Microspheres
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.
| Study group | Role | What they receive |
|---|---|---|
| Comparative performance of ceVUS & VCUG | Experimental | 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. Receives: Drug: OPTISON |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 10-15 minutes.
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.
Measured: Within 1 hour and up to 2 days after ceVUS and VCUG examinations completion.
Secondary outcomes (1)
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.
Measured: 10-15 minutes.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted31 Jul 2014 (estimated)
- Study startJul 2014
- Primary completionMar 2016
- Study completionMar 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Vesico-Ureteral RefluxStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Diagnosis
- Allocation
- Not applicable
- Intervention model
- Single group
- 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)
- Enrolment
- 31 participants (actual)
Sponsor and investigators
- Lead sponsor
- Kassa Darge
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Kassa Darge, Children's Hospital of Philadelphia
- Investigators
- Kassa Darge, MD, PhD, Principal investigator, Department of Radiology, the Children's Hospital of Philadelphia
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02204917
- Sponsor's protocol ID
- IRB 13-010618
- Acronym
- ceVUS
- Status last verified
- Oct 2018
- First submitted
- 25 Jun 2014
- Last updated
- 27 Nov 2018
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 27 Nov 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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.
- ClinicalTrials.gov ID
- NCT02204917
- Acronym / sponsor ID
- ceVUS / IRB 13-010618
- Conditions
- Vesico-Ureteral Reflux
- Keywords
- Ultrasound, Ultrasound Contrast Agents, Optison, contrast enhanced Voiding Urosonography (ceVUS), ceVUS, Vesicoureteral Reflux, Children, Kidney
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 31 participants (actual)
- Lead sponsor
- Kassa DargeUniversity, hospital or other
- Study start
- Jul 2014
- Primary completion
- Mar 2016 (actual)
- Study completion
- Mar 2017 (actual)
- First posted
- 31 Jul 2014 (estimated)
- Results
- Posted 27 Nov 2018
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Diagnosis
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- Comparative performance of contrast enhanced Voiding Urosonography (ceVUS) and Voiding Cystourethrography (VCUG) in the same participant and in the same session.
| Arm | Type | Receives |
|---|---|---|
| Comparative performance of ceVUS & VCUG | Experimental | Drug: OPTISONContrast 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. |
Who may qualify
- Ages
- Up to 18 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (4 listed)
- 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.
Key exclusion criteria (3 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| OPTISONAlso: Perflutren Protein-Type A MicrospheresContrast 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. | Drug | Comparative performance of ceVUS & VCUG |
Primary outcome
Number of Pelvic-ureter-units (PUUs) Detected With Vesicoureteral Reflux by Contrast Enhanced Voiding Urosonography (ceVUS) and by Voiding Cystourethrography (VCUG).
Time frame: 10-15 minutes.
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.
Number of Participants With Adverse Events Following Contrast Enhanced Voiding Urosonography (ceVUS) With OPTISON and Voiding Cystourethrography (VCUG).
Time frame: 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.
1 secondary outcome
Compare the Diagnostic Accuracy of Contrast Enhanced Voiding Urosonography (ceVUS) With Voiding CystoUrethroGraphy (VCUG) for Vesicoureteral Reflux Detection and Urethral Imaging in Children.
Time frame: 10-15 minutes.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Nov 2018.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Related trials for Vesico-Ureteral Reflux
Not yet recruitingPhase 1
Radiation-Free Technique for Evaluating Renal Scarring (RAFTERS)
Vesico-Ureteral Reflux
RecruitingPhase 3
Spinal Morphine or Intravenous Lidocaine in Robot-assisted Upper Urologic Surgery
Other Specified Disorders of Kidney and Ureter, Benign Neoplasm of Ureter
Not yet recruiting
Diagnostic Performance of PIC Cystogram vs VCUG in Children
Pediatric Urology
Recruiting
Diagnosing Vesicoureteric Reflux in Children by Direct Isotope Cystography and Contrast Enhanced Voiding Ultrasonography
VUR - Vesicoureteric Reflux
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Kassa Darge, MD, PhD principal investigator
Department of Radiology, the Children's Hospital of Philadelphia
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing OPTISON in people with Vesico-Ureteral Reflux, run by Kassa Darge at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 3 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 27 Nov 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 27 Nov 2018). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Pelvic-ureter-units (PUUs) Detected With Vesicoureteral Reflux by Contrast Enhanced Voiding Urosonography (ceVUS) and by Voiding Cystourethrography (VCUG). (time frame: 10-15 minutes.). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Nov 2018.