Chronic Kidney Disease, Cystic Kidney Disease
Conditions
Brief summary
The purpose of this research study is to evaluate contrast-enhanced ultrasound for kidney malignancies
Detailed description
This is an investigator-initiated, prospective study designed to evaluate the accuracy of contrast-enhanced ultrasound (CEUS) with microbubble contrast agent (perflutren lipid; Definity®) to identify malignancy in patients with kidney disease, a known risk factor for kidney malignancy, in whom a conventional ultrasound (US) shows an indeterminate cystic kidney lesion. The primary objective of the study is to estimate the sensitivity of CEUS in diagnosing kidney malignancy in patients with a risk factor for kidney malignancy and compare it to the current gold standard test in this patient population. Secondary analysis will include more optimal contrast-enhanced imaging with computed tomography (CT) or magnetic resonance imaging (MRI) in a subset of patients who can receive these studies. The study outcome will lead to immediate clinical application in patients with chronic kidney disease. Given the cost-effectiveness and adverse event profile, it has excellent potential to become established as first line diagnostics in the general patient population as well.
Interventions
Dosing per approved package label
Sponsors
Vanderbilt University
North Carolina Translational and Clinical Sciences Institute
University of North Carolina, Chapel Hill
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
DIAGNOSTIC
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
To be eligible for the present study, patients must meet the following criteria: 1. Able to provide written informed consent 2. Willing to comply with protocol requirements 3. At least 18 years of age 4. Have kidney disease, defined as either CKD II-VI, determined by estimated glomerular filtration rate (GFR) of \<90 and derived from serum creatinine measurements, or albuminuria/proteinuria, determined by albumin to creatinine ratio or protein to creatinine ratio of \>30mg/gm, or having received a kidney transplant 5. Have at least one kidney lesion identified but incompletely characterized on a non-contrasted US, CT, or MR exam for which the patient's provider recommends follow-up studies or further evaluation with an additional imaging tests.
Exclusion criteria
Patients who meet any of the following criteria will be excluded for enrollment: 1. Critically ill or medically unstable and whose critical course during the observation period would be unpredictable (e.g., chronic obstructive pulmonary disease (COPD) requiring oxygen) 2. Known hypersensitivity to sulfur hexafluoride or to any component of perflutren lipid (Definity®) 3. Right to left shunt, severe pulmonary hypertension (Pulmonary artery pressure \>90mmHg), or adult respiratory distress syndrome 4. Active cardiac disease including any of the following: * Severe congestive heart failure (class IV in accordance with the classification of the New York Heart Association) * Unstable angina. * Severe arrhythmia (i.e. ventricular tachycardia, flutter fibrillation; ventricular premature complexes occurring close to the preceding T- wave, multifocal complexes). * Myocardial infarction within 14 days prior to the date of proposed Definity® administration. * Uncontrolled systemic hypertension (systolic blood pressure (BP) \>180 mm Hg and/or diastolic BP \>100 mm Hg despite optimal medical management 5. Is in an intensive care setting 6. Has an unstable neurological disease (e.g cerebrovascular accident (including transient ischemic attacks (TIAs) within the 3 months before signing of informed consent 7. Has undergone an invasive procedure on kidney lesion (e.g. tissue biopsy, surgery, nonsurgical cytoreductive procedure) since identification of lesion via US without contrast 8. 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 9. Female patient who is pregnant or lactating (the possibility of pregnancy has to be excluded by negative serum or urine beta human chorionic gonadotropin results, obtained within 24 hours before the perflutren lipid administration, or on the basis of patient history, e.g.: tubal ligation, hysterectomy or a minimum of 1 year without menses) 10. Obesity that limits obtainment of acceptable images \-
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Lesions With a Change in Radiologist's Evaluation | Baseline, 1 year | Lesions will be assessed for change in size, calcification, and septation based on Bosniak criteria (I, II, IIF, III, IV) to determine whether a lesion has progressed, regressed, or is stable. |
| Sensitivity of Qualitative Interpretations of CEUS in Diagnosing Kidney Malignancy | Baseline, 1 year | PRELIMINARY RESULTS of sensitivity of qualitative interpretations of CEUS in diagnosing kidney malignancy in patients with CKD and a suspicious or indeterminate lesion on non-contrasted imaging compared to the truth standard |
| Specificity of Qualitative Interpretations of CEUS | Baseline, 1 year | PRELIMINARY RESULTS of specificity of qualitative interpretations of CEUS in diagnosing kidney malignancy in patients with CKD and a suspicious or indeterminate lesion on non-contrasted imaging compared to the truth standard |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Specificity of Quantitative Metrics Generated From CEUS in Diagnosing Kidney Malignancy in Patients With CKD and a Suspicious or Indeterminate Lesion on Non-contrasted Imaging Compared to the Truth Standard | Baseline, 1 Year | Specificity of Quantitative Metrics Generated From CEUS in Diagnosing Kidney Malignancy in Patients With CKD and a Suspicious or Indeterminate Lesion on Non-contrasted Imaging Compared to the Truth Standard |
| Sensitivity of Quantitative Metrics Generated From CEUS in Diagnosing Kidney Malignancy in Patients With CKD and a Suspicious or Indeterminate Lesion on Non-contrasted Imaging Compared to the Truth Standard | Baseline, 1 Year | Sensitivity of Quantitative Metrics Generated From CEUS in Diagnosing Kidney Malignancy in Patients With CKD and a Suspicious or Indeterminate Lesion on Non-contrasted Imaging Compared to the Truth Standard |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Perflutren Lipid Microsphere Activate by shaking for 45 seconds using VIALMIX. Use activated product within 5 minutes. Infusion: The recommended infusion dose for activated perflutren is via an IV infusion of 1.3 mL added to 50 mL of preservative-free saline. The rate of infusion should be initiated at 4.0 mL/minute, but titrated as necessary to achieve optimal image enhancement, not to exceed 10 mL/minute per P.I. approval
Perflutren lipid microsphere: Dosing per approved package label | 63 |
| Total | 63 |
Baseline characteristics
| Characteristic | Perflutren Lipid Microsphere |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 25 Participants |
| Age, Categorical Between 18 and 65 years | 38 Participants |
| Age, Continuous | 59 years STANDARD_DEVIATION 15 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 62 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 28 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 2 Participants |
| Race (NIH/OMB) White | 33 Participants |
| Region of Enrollment United States | 63 Participants |
| Sex: Female, Male Female | 20 Participants |
| Sex: Female, Male Male | 43 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 63 |
| other Total, other adverse events | 1 / 63 |
| serious Total, serious adverse events | 0 / 63 |
Outcome results
Primary
Number of Lesions With a Change in Radiologist's Evaluation
Lesions will be assessed for change in size, calcification, and septation based on Bosniak criteria (I, II, IIF, III, IV) to determine whether a lesion has progressed, regressed, or is stable.
Time frame: Baseline, 1 year
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Perflutren Lipid Microsphere | Number of Lesions With a Change in Radiologist's Evaluation | 24 lesions |
Primary
Sensitivity of Qualitative Interpretations of CEUS in Diagnosing Kidney Malignancy
PRELIMINARY RESULTS of sensitivity of qualitative interpretations of CEUS in diagnosing kidney malignancy in patients with CKD and a suspicious or indeterminate lesion on non-contrasted imaging compared to the truth standard
Time frame: Baseline, 1 year
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Perflutren Lipid Microsphere | Sensitivity of Qualitative Interpretations of CEUS in Diagnosing Kidney Malignancy | 75 percentage of positive scans |
Primary
Specificity of Qualitative Interpretations of CEUS
PRELIMINARY RESULTS of specificity of qualitative interpretations of CEUS in diagnosing kidney malignancy in patients with CKD and a suspicious or indeterminate lesion on non-contrasted imaging compared to the truth standard
Time frame: Baseline, 1 year
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Perflutren Lipid Microsphere | Specificity of Qualitative Interpretations of CEUS | 71 percentage of negative scans |
Secondary
Sensitivity of Quantitative Metrics Generated From CEUS in Diagnosing Kidney Malignancy in Patients With CKD and a Suspicious or Indeterminate Lesion on Non-contrasted Imaging Compared to the Truth Standard
Sensitivity of Quantitative Metrics Generated From CEUS in Diagnosing Kidney Malignancy in Patients With CKD and a Suspicious or Indeterminate Lesion on Non-contrasted Imaging Compared to the Truth Standard
Time frame: Baseline, 1 Year
Population: Quantitative analysis unable to be conducted on cystic lesions and required solid portions, so data was not collected
Secondary
Specificity of Quantitative Metrics Generated From CEUS in Diagnosing Kidney Malignancy in Patients With CKD and a Suspicious or Indeterminate Lesion on Non-contrasted Imaging Compared to the Truth Standard
Specificity of Quantitative Metrics Generated From CEUS in Diagnosing Kidney Malignancy in Patients With CKD and a Suspicious or Indeterminate Lesion on Non-contrasted Imaging Compared to the Truth Standard
Time frame: Baseline, 1 Year
Population: Quantitative analysis unable to be conducted on cystic lesions and required solid portions, so data was not collected