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Contrast-enhanced Ultrasound as a Screening Tool for Kidney Cancer in Patients With Von-Hippel Lindau (CEUS-VHL)

Primary Purpose

Von-Hippel Lindau, Kidney Disease, Chronic

Status

Completed

Phase

Phase 2

Locations

United States

Study Type

Interventional

Intervention

Perflutren lipid microsphere

Sulfur hexafluoride lipid microspheres

About this trial

This is an interventional diagnostic trial for Von-Hippel Lindau

Eligibility Criteria

16 Years - 99 Years (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

To be eligible for the present study, patients must meet the following criteria:

Able to provide written informed consent
Willing to comply with protocol requirements
At least 16 years of age
Carry a diagnosis of VHL and able to undergo routine clinical screening tests for RCC

Exclusion Criteria:

Critically ill or medically unstable or in an intensive care setting and whose critical course during the observation period would be unpredictable
Known hypersensitivity to sulfur hexafluoride or to any component of perflutren lipid (Definity®) or sulfur hexafluoride (Lumason®)
Right to left shunt, severe pulmonary hypertension (Pulmonary artery pressure >90mmHg), or adult respiratory distress syndrome
Active cardiac disease including any of the following:
A. Severe congestive heart failure (class IV in accordance with the classification of the New York Heart Association) B.Unstable angina. C.Symptomatic arrhythmia (i.e. tachycardia, bradycardia, supraventricular tachycardia, ventricular fibrillation, ventricular tachycardia, atrial flutter or fibrillation).
D.Myocardial infarction within 14 days prior to the date of proposed microbubble administration.
Has any other medical condition or other circumstances that would significantly decrease the chances of obtaining reliable data or of achieving the study objectives such as:
- Mental illness
- Drug abuse
Female patient who is pregnant or lactating
Obesity that limits obtainment of acceptable images

Sites / Locations

University of North Carolina of Chapel hill

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Perflutren Lipid Microsphere or Lumason

Arm Description

Patients with Von-Hippel Lindau disease will be imaged using contrast-enhanced ultrasound with either perflutren or Lumason.

Outcomes

Primary Outcome Measures

Change in Radiologist's Lesion Evaluation compared to B-mode Ultrasound (percent)

Kappas will be calculated separately for each reader for CEUS versus B-mode US using the dichotomized Bosniak score. Confidence intervals for kappas will be computed by bootstrapping subjects, accounting for potential correlations of kidneys within subjects. Differences in agreement between readers will be based on comparing reader specific kappas, with statistical significance of these differences tested via bootstrapping. An overall kappa will be computed for each paired imaging comparison by averaging kappas across readers, with a 95% interval calculated via bootstrapping. Differences in overall kappas for the 3 paired imaging comparisons will be assessed using a bootstrap test.

Secondary Outcome Measures

Change in Radiologist's Lesion Evaluation compared to contrasted MRI (percent)

Kappas will be calculated separately for each reader for CEUS versus contrasted MRI using the dichotomized Bosniak score. Confidence intervals for kappas will be computed by bootstrapping subjects, accounting for potential correlations of kidneys within subjects. Differences in agreement between readers will be based on comparing reader specific kappas, with statistical significance of these differences tested via bootstrapping. An overall kappa will be computed for each paired imaging comparison by averaging kappas across readers, with a 95% interval calculated via bootstrapping. Differences in overall kappas for the 3 paired imaging comparisons will be assessed using a bootstrap test.

Full Information

NCT ID

NCT03907657

First Posted

April 5, 2019

Last Updated

March 20, 2023

Sponsor

UNC Lineberger Comprehensive Cancer Center

Collaborators

Lantheus Medical Imaging

1. Study Identification

Unique Protocol Identification Number

NCT03907657

Brief Title

Contrast-enhanced Ultrasound as a Screening Tool for Kidney Cancer in Patients With Von-Hippel Lindau

Acronym

CEUS-VHL

Official Title

Double-Center Cross-Sectional Study of Contrast-Enhanced Ultrasound With Lumason/Definity as a Screening Tool for Kidney Cancer in Patients With Von-Hippel Lindau

Study Type

Interventional

2. Study Status

Record Verification Date

March 2023

Overall Recruitment Status

Completed

Study Start Date

September 23, 2019 (Actual)

Primary Completion Date

March 13, 2023 (Actual)

Study Completion Date

March 13, 2023 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

UNC Lineberger Comprehensive Cancer Center

Collaborators

Lantheus Medical Imaging

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

Yes

5. Study Description

Brief Summary

The purpose of this study is to determine if contrast-enhanced ultrasound can detect abnormal features of kidney lesions in patients with Von-Hippel Lindau with the same accuracy as conventional ultrasound and contrast-enhanced magnetic resonance imaging (MRI)

Detailed Description

This is a pilot cross-sectional study that compares contrast enhanced ultrasound to conventional ultrasound and contrasted MRI. Any patient undergoing annual imaging screening is eligible, but the investigators will target inclusion of at least 10 subjects who have at least 1 kidney lesion. Therefore, up to 5 subjects may have no current kidney lesions. Subject participation will be only for the day of CEUS study. There will be no follow-up period for this study. However, if results are encouraging, a longitudinal observational study may follow, and these same subjects would be eligible for enrollment. Eligible subjects will undergo a contrast enhanced ultrasound. Following completion of imaging, all CEUS, MRI (within 4 months) and B-mode (at time of CEUS) US studies will be de-identified. Blinded radiologists will interpret images and provide an overall assessment of risk of malignancy to each kidney using the Bosniak criteria for each kidney lesion present. The Bosniak criteria places cystic lesions into one of 5 categories (I, II, IIF, III and IV) based on lesion characteristics. CEUS based diagnosis will be compared to the diagnoses on routine B-mode US and contrast-enhanced MRI.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Von-Hippel Lindau, Kidney Disease, Chronic

7. Study Design

Primary Purpose

Diagnostic

Study Phase

Phase 2

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

15 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Perflutren Lipid Microsphere or Lumason

Arm Type

Experimental

Arm Description

Patients with Von-Hippel Lindau disease will be imaged using contrast-enhanced ultrasound with either perflutren or Lumason.

Intervention Type

Drug

Intervention Name(s)

Perflutren lipid microsphere

Other Intervention Name(s)

• Definity®, • Microbubble contrast agent

Intervention Description

Baseline B-mode US will be performed to confirm the lesions being imaged (unless it is a subject with no lesions, then a basic B-mode US will be performed. Perflutren is a diagnostic drug that is intended to be used for contrast enhancement. The vial contains a clear, colorless, sterile, non-pyrogenic, hypertonic solution which is activated by mechanical agitation with Vialmix®.It will be dispensed in inactivated form to a study team member. The contrast agent will be activated just prior to administration (ideally to be used within 5 minutes of activation). Contrast agent Definity (or Lumason) will be activated according to package insert instructions, including use of VialMix®, the device used to activate Definity. Administration will occur IV in coordination with sonography staff trained specifically in contrast ultrasound imaging.The total imaging time is anticipated to be less than 30 minutes.

Intervention Type

Drug

Intervention Name(s)

Sulfur hexafluoride lipid microspheres

Other Intervention Name(s)

Lumason

Intervention Description

Baseline B-mode US will be performed to confirm the lesions being imaged (unless it is a subject with no lesions, then a basic B-mode US will be performed. Lumason will be used as a secondary contrast agent only if Definity(perflutren) is unavailable.This drug will be administered using the dosing range and administration type within the Lumason prescribing information. The contrast agent will be activated just prior to administration (ideally to be used within 5 minutes of activation). Contrast agent Definity (or Lumason) will be activated according to package insert instructions, including use of VialMix®, the device used to activate Definity. Administration will occur IV in coordination with sonography staff trained specifically in contrast ultrasound imaging.The total imaging time is anticipated to be less than 30 minutes.

Primary Outcome Measure Information:

Title

Change in Radiologist's Lesion Evaluation compared to B-mode Ultrasound (percent)

Description

Time Frame

(Baseline)

Secondary Outcome Measure Information:

Title

Change in Radiologist's Lesion Evaluation compared to contrasted MRI (percent)

Description

Time Frame

(Baseline, 4 months)

10. Eligibility

Sex

All

Minimum Age & Unit of Time

16 Years

Maximum Age & Unit of Time

99 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: To be eligible for the present study, patients must meet the following criteria: Able to provide written informed consent Willing to comply with protocol requirements At least 16 years of age Carry a diagnosis of VHL and able to undergo routine clinical screening tests for RCC Exclusion Criteria: Critically ill or medically unstable or in an intensive care setting and whose critical course during the observation period would be unpredictable Known hypersensitivity to sulfur hexafluoride or to any component of perflutren lipid (Definity®) or sulfur hexafluoride (Lumason®) Right to left shunt, severe pulmonary hypertension (Pulmonary artery pressure >90mmHg), or adult respiratory distress syndrome Active cardiac disease including any of the following: A. Severe congestive heart failure (class IV in accordance with the classification of the New York Heart Association) B.Unstable angina. C.Symptomatic arrhythmia (i.e. tachycardia, bradycardia, supraventricular tachycardia, ventricular fibrillation, ventricular tachycardia, atrial flutter or fibrillation). D.Myocardial infarction within 14 days prior to the date of proposed microbubble administration. Has any other medical condition or other circumstances that would significantly decrease the chances of obtaining reliable data or of achieving the study objectives such as: Mental illness Drug abuse Female patient who is pregnant or lactating Obesity that limits obtainment of acceptable images

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Emily Chang, MD

Organizational Affiliation

University of North Carolina, Chapel Hill

Official's Role

Principal Investigator

Facility Information:

Facility Name

University of North Carolina of Chapel hill

City

Chapel Hill

State/Province

North Carolina

ZIP/Postal Code

27599-7510

Country

United States

12. IPD Sharing Statement

Plan to Share IPD

Citations:

PubMed Identifier

34783716

Citation

Larcher A, Rowe I, Belladelli F, Fallara G, Raggi D, Necchi A, Montorsi F, Capitanio U, Salonia A; OSR VHL Program. Von Hippel-Lindau disease-associated renal cell carcinoma: a call to action. Curr Opin Urol. 2022 Jan 1;32(1):31-39. doi: 10.1097/MOU.0000000000000950.

Results Reference

derived

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Contrast-enhanced Ultrasound as a Screening Tool for Kidney Cancer in Patients With Von-Hippel Lindau

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