Contrast Enhanced Ultrasound for Kidney Obstruction

Overseen By Sapan N Ambani, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: University of Michigan

Disqualifiers: Solitary kidney, Vesicoureteral reflux, BMI >=40, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 2

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a special contrast agent called Definity (also known as Perflutren Lipid Microsphere) to determine if it can enhance ultrasound images of kidney blockages. Although typically used for the heart and liver, researchers aim to assess its effectiveness for kidney issues as well. Individuals with a kidney blockage planning surgery to address it might be suitable candidates. Participants will visit twice: once before and once after their surgery. As a Phase 2 trial, this research focuses on evaluating the treatment's effectiveness in an initial, smaller group of people.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

What prior data suggests that this ultrasound contrast agent is safe for evaluating kidney obstruction?

Research has shown that Definity, a special liquid used in ultrasound scans, is generally safe. The FDA has already approved it for heart and liver imaging. Studies have found that most people, even those with heart and lung problems, tolerate it well. However, serious reactions affecting the heart and lungs can occur, so discussing any concerns with a doctor is important. Overall, evidence supports the safety of Definity, but individual reactions to treatments can vary. Always discuss potential risks with healthcare providers. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for kidney obstruction?

Most treatments for kidney obstruction rely on imaging techniques like CT scans or MRIs, which can be time-consuming and expose patients to radiation. However, the use of Definity in contrast-enhanced ultrasound offers a unique advantage. Definity is a contrast agent that enhances ultrasound images, providing clearer and more detailed views of kidney function without the need for radiation. Researchers are excited because this method could make diagnosing obstructions faster and safer, offering a non-invasive alternative that might be more comfortable for patients.

What evidence suggests that this ultrasound imaging technique is effective for evaluating kidney obstruction?

Research has shown that Definity, a special liquid used in ultrasound tests, reliably checks the liver and heart. In a study with 1,060 patients, Definity proved safe, with no deaths or serious side effects. The FDA has approved it for these purposes. This treatment clarifies ultrasound images, aiding in problem detection. In this trial, researchers are testing Definity as a contrast agent for kidney checks to better identify issues like blockages. This suggests Definity might be useful for diagnosing kidney blockages. ^{6 7 8 9 10}

Who Is on the Research Team?

Sapan N Ambani, MD

Principal Investigator

University of Michigan

Are You a Good Fit for This Trial?

This trial is for individuals with confirmed unilateral kidney obstruction planning surgery to correct it. They must have had a specific renal scan within the last 6 months and not have a solitary kidney, abnormalities in the other kidney, severe allergies to ultrasound contrast agents or certain ingredients, be pregnant/breastfeeding, extremely overweight without prior imaging confirmation, very poor overall kidney function, known reflux into kidneys or an unstable heart condition.

Inclusion Criteria

I have chosen surgery to fix a blockage in my urinary system.

My kidney scan shows a blockage in one kidney.

My kidney is blocked but still works more than 15%, confirmed by a recent scan.

Exclusion Criteria

I have issues with my opposite kidney, like swelling or stones.

I do not have any recent serious heart or lung problems.

I have a tube inserted to help my kidney drain urine.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Pre-Surgery Evaluation

Participants undergo ultrasound imaging with Definity contrast agent before planned surgery

1 day

1 visit (in-person)

Post-Surgery Evaluation

Participants undergo ultrasound imaging with Definity contrast agent after planned surgery

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Definity

Trial Overview The study tests Definity contrast during ultrasound on patients with kidney obstruction before and after their corrective surgery. It aims to evaluate if this FDA-approved agent for liver and heart can also effectively assess kidney obstructions using enhanced imaging techniques.

How Is the Trial Designed?

Group I: Definity contrast agent Experimental Treatment 1 Intervention

Who Is Running the Clinical Trial?

University of Michigan

Lead Sponsor

Trials

1,891

Recruited

6,458,000+

Published Research Related to This Trial

Microbubbles enhanced ultrasound contrast is an effective and cost-efficient technique for assessing renal masses, aiding in the differential diagnosis of conditions like pseudotumors and monitoring small renal masses.

While this technique offers real-time insights into renal perfusion and microcirculation, it does have limitations such as rapid contrast washout, operator dependency, and the need for specialized software for accurate interpretation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bibliographic review about the usefulness of ultrasound contrast media in the study of renal masses. Sanz Mayayo, E., Hevia Palacios, V., Arias Fúnez, F., et al.[2016]

The experimental microbubble-based ultrasound contrast agent (Imagent US) significantly improved the visualization of renal perfusion in rabbits, with effective enhancement observed even at low doses (0.007 mL/kg).

The contrast agent allowed for clear differentiation between normally perfused and ischemic kidney areas, indicating its potential utility in identifying focal perfusion abnormalities in renal imaging.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Renal cortical perfusion in rabbits: visualization with color amplitude imaging and an experimental microbubble-based US contrast agent. Taylor, GA., Ecklund, K., Dunning, PS.[2016]

In a study involving 4,786 patients undergoing stress echocardiography, the use of perflutren-based contrast agents like Definity and Optison did not increase the risk of severe adverse events compared to patients who did not receive contrast.

The rates of serious complications, including death within 24 hours and cardiac arrest, were similar between those receiving contrast and those who did not, indicating that the use of these contrast agents is generally safe in this context.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety of ultrasound contrast agents in stress echocardiography. Gabriel, RS., Smyth, YM., Menon, V., et al.[2015]

In response to serious safety concerns, including 4 patient deaths and 190 serious reactions, the FDA issued a 'black box' warning for ultrasound contrast agents Definity and Optison, leading to a significant decline in their use in the US.

Recent safety data and discussions from the FDA Cardio-Renal panel indicate ongoing evaluation of these agents, with revised labeling aimed at improving safety protocols for contrast echocardiography.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ultrasound contrast agents: balancing safety versus efficacy. Main, ML., Goldman, JH., Grayburn, PA.[2022]

In a study involving 1,060 patients, Definity (perflutren lipid microsphere) was found to be well tolerated, with no deaths or serious adverse events reported during or within 30 minutes after administration.

The overall adverse event rate was 10.8%, with a low drug-related adverse event rate of 3.5%, indicating that most adverse events were mild or moderate, making Definity a safe option for patients with suboptimal echocardiograms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CaRES (Contrast Echocardiography Registry for Safety Surveillance): a prospective multicenter study to evaluate the safety of the ultrasound contrast agent definity in clinical practice. Weiss, RJ., Ahmad, M., Villanueva, F., et al.[2022]

In the first year of using the second-generation contrast agent Definity in echocardiography, 161 patients showed a significant improvement in endocardial definition scores (p=0.0001), enhancing the clarity of heart imaging.

The use of contrast echocardiography led to the detection of clinically significant conditions that were missed in standard 2D imaging, with a very low adverse event rate of only 0.6%, indicating its safety and efficacy in clinical practice.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Contrast echocardiography in Australian clinical practice. Hamilton-Craig, C., Boga, T., West, C., et al.[2022]

Contrast-enhanced ultrasonography (CEUS) significantly improves the assessment of renal masses and complex cysts compared to traditional ultrasound, providing accurate differentiation between benign and malignant lesions.

CEUS is a safe imaging option for patients with renal failure, as it avoids the risks associated with CT and MRI contrast agents, and offers real-time imaging without ionizing radiation, making it a cost-effective alternative.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Role of US Contrast Agents in the Assessment of Indeterminate Solid and Cystic Lesions in Native and Transplant Kidneys. Harvey, CJ., Alsafi, A., Kuzmich, S., et al.[2016]

Contrast-enhanced ultrasound (CEUS) effectively evaluates renal microperfusion changes in a rat model of chronic intermittent hypoxia (CIH), which simulates obstructive sleep apnea, showing significant differences in parameters like peak intensity and time to peak between CIH and control groups.

CEUS parameters correlated with kidney function markers, indicating that CEUS is a safe and accurate method for assessing renal microvascular damage, as evidenced by the significant relationships between CEUS findings and serum creatinine levels.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Contrast Enhanced Ultrasonography of Kidney in Chronic Intermittent Hypoxia Rat Model. Lun, H., Liu, R., Hu, Q., et al.[2023]

In a study of 96,705 transthoracic echocardiograms involving 63,189 adults, the use of perflutren ultrasound contrast agents was not linked to an increased risk of 1-day mortality, with only 0.44% of patients in the contrast group dying compared to 0.69% in the non-contrast group.

The analysis showed that contrast use did not significantly affect mortality rates even after adjusting for various factors like age, gender, and co-morbidities, suggesting that the benefits of using contrast agents for better imaging should not be overlooked.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Administration of perflutren contrast agents during transthoracic echocardiography is not associated with a significant increase in acute mortality risk. Goldberg, YH., Ginelli, P., Siegel, R., et al.[2014]

Novel ultrasound techniques, such as renal elastography and ultrasensitive Doppler, show promise for noninvasive assessment of kidney conditions, particularly in diagnosing renal fibrosis, which is crucial given the rising rates of chronic kidney disease.

Contrast-enhanced ultrasound using microbubble agents is well tolerated and can enhance the evaluation of renal masses and vascular disorders, even in patients with impaired kidney function, although these agents are not yet approved for clinical use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ultrasound-based imaging methods of the kidney-recent developments. Correas, JM., Anglicheau, D., Joly, D., et al.[2022]

Contrast-enhanced ultrasound (CEUS) is a safe and well-tolerated imaging technique for kidney evaluation, offering a non-nephrotoxic alternative to CT or MRI, which is particularly beneficial for patients with kidney concerns.

CEUS is effective in diagnosing various renal conditions, including renal tumors and acute pyelonephritis, and may also be useful for monitoring kidney health after treatments, highlighting its expanding applications in renal medicine.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Current and potential renal applications of contrast-enhanced ultrasound. McArthur, C., Baxter, GM.[2016]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT05090800

Contrast Enhanced Ultrasound for Renal Obstruction This research is studying Definity ultrasound contrast agent, which is already approved by the Food and Drug Administration (FDA) for the ultrasound evaluation ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6873806/

An Introduction to Contrast-Enhanced Ultrasound for ... CEUS is an emerging imaging technique that may have clinically useful applications for detecting malignant kidney lesions, specifically in patients with CKD.

3. withpower.com withpower.com/trial/phase-3-9-2021-84585

Contrast Enhanced Ultrasound for Kidney Obstruction In a study involving 1,060 patients, Definity (perflutren lipid microsphere) was found to be well tolerated, with no deaths or serious adverse events reported ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC2948414/

Contrast Enhanced Diagnostic Ultrasound Causes Renal ... Glomerular capillary hemorrhage (GCH) has been reported and confirmed as a consequence of contrast-enhanced diagnostic ultrasound (CEDUS) of rat kidney.

5. definityimaging.com definityimaging.com/efficacy

Demonstrating the Efficacy of DEFINITY® in Clinical Settings DEFINITY® reduces the number of diagnostic procedures conducted, decreases length of stay, and lowers the per-patient expense.

6. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/label/2011/021064s011lbl.pdf

Definity (perflutren) injection label - accessdata.fda.gov These highlights do not include all of the information needed to use. DEFINITY® safely and effectively. See full prescribing information for. DEFINITY®.

7. definityimaging.com definityimaging.com/safety

Safety Profile of DEFINITY® for Medical Imaging DEFINITY® is demonstrated to be safe in patients with a high prevalence of cardiopulmonary disease and pulmonary hypertension.

8. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/label/2021/021064s025s029lbl.pdf

Definity - accessdata.fda.gov WARNING: SERIOUS CARDIOPULMONARY REACTIONS. See full prescribing information for complete boxed warning. Serious cardiopulmonary reactions, including ...

9. go.drugbank.com go.drugbank.com/drugs/DB00556

Perflutren: Uses, Interactions, Mechanism of Action Perflutren is a diagnostic medication to improve contrast during echocardiograms.

10. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC3840100/

RENAL RETENTION OF LIPID MICROBUBBLES Although the safety of commercially-produced microbubbles has been established by trials that evaluated serious reactions, post-marketing surveys and ...