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

10 Participants Needed

Trial Summary

What is the purpose of this trial?

This research is studying Definity ultrasound contrast agent, which is already approved by the Food and Drug Administration (FDA) for the ultrasound evaluation of the liver and heart. This research will investigate the ability to use ultrasound imaging with ultrasound contrast agents to evaluate kidney obstruction. Eligible participants that are enrolled will have two visits (one before and one after the planned surgery to relieve the kidney obstruction).

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 data supports the effectiveness of the drug Definity for kidney obstruction?

While there is no direct evidence for Definity's effectiveness in treating kidney obstruction, it is used as an ultrasound contrast agent to improve imaging in other conditions, like heart imaging. This suggests it might help in better visualizing kidney structures, which could be useful in assessing kidney obstruction. ^{1 2 3 4 5}

Is the ultrasound contrast agent Definity safe for use in humans?

Definity, an ultrasound contrast agent, has been associated with some serious heart and lung reactions, including a few deaths, leading to FDA warnings. However, studies show that severe adverse reactions are uncommon, and using Definity does not significantly increase the risk of severe events during stress echocardiography. ^{1 2 3 6 7}

How does contrast-enhanced ultrasound differ from other treatments for kidney obstruction?

Contrast-enhanced ultrasound (CEUS) is unique because it uses microbubble contrast agents to provide real-time imaging of kidney blood flow and microcirculation without the risks associated with CT or MR imaging contrast agents. This method is safe, well-tolerated, and does not expose patients to ionizing radiation, making it a novel option for evaluating kidney obstruction. ^{4 8 9 10 11}

Research Team

Sapan N Ambani, MD

Principal Investigator

University of Michigan

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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]

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 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]

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]

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]

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]

References

1. United States 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. [2022]

2. Australia pubmed.ncbi.nlm.nih.gov

Contrast echocardiography in Australian clinical practice. [2022]

3. England pubmed.ncbi.nlm.nih.gov

Ultrasound contrast agents: balancing safety versus efficacy. [2022]

4. United States pubmed.ncbi.nlm.nih.gov

Renal cortical perfusion in rabbits: visualization with color amplitude imaging and an experimental microbubble-based US contrast agent. [2016]

5. United States pubmed.ncbi.nlm.nih.gov

Ultrasound-based imaging methods of the kidney-recent developments. [2022]

6. United States pubmed.ncbi.nlm.nih.gov

Safety of ultrasound contrast agents in stress echocardiography. [2015]

7. Switzerland pubmed.ncbi.nlm.nih.gov

Administration of perflutren contrast agents during transthoracic echocardiography is not associated with a significant increase in acute mortality risk. [2014]

8. England pubmed.ncbi.nlm.nih.gov

Current and potential renal applications of contrast-enhanced ultrasound. [2016]

9. Spain pubmed.ncbi.nlm.nih.gov

Bibliographic review about the usefulness of ultrasound contrast media in the study of renal masses. [2016]

10. United States pubmed.ncbi.nlm.nih.gov

Role of US Contrast Agents in the Assessment of Indeterminate Solid and Cystic Lesions in Native and Transplant Kidneys. [2016]

11. England pubmed.ncbi.nlm.nih.gov

Contrast Enhanced Ultrasonography of Kidney in Chronic Intermittent Hypoxia Rat Model. [2023]