Ultrasound Elastography for Predicting Sinusoidal Obstruction Syndrome

Recruiting at 6 trial locations

Overseen By Maura Sien, MSML, CCRC

Age: Any Age

Sex: Any

Trial Phase: Academic

Sponsor: Children's Mercy Hospital Kansas City

Disqualifiers: Pregnancy, Prisoners, Wards, others

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

Compensation: Varies

Number of Visits: 13

250 Participants Needed

Trial Summary

What is the purpose of this trial?

To perform an receiver operating characteristic (ROC) analysis, define a threshold and quantify the sensitivity and specificity of US SWE for risk stratification of patients into three categories as defined by the European Bone Marrow Transplant (EBMT) adult and pediatric criteria: no sinusoidal obstruction syndrome (SOS), mild to moderate SOS, and severe to very severe SOS. Secondarily, the investigators would also like to quantify the temporal relationship between US SWE changes and SOS diagnosis according to various clinical criteria (Modified Seattle, Baltimore, EBMT consortium).

Do I need to stop my current medications for this trial?

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 treatment Ultrasound Elastography for predicting Sinusoidal Obstruction Syndrome?

Ultrasound elastography has shown promise in assessing tissue stiffness in various conditions, such as liver fibrosis and Crohn's disease, by providing non-invasive and cost-effective imaging. This suggests it could be useful for predicting Sinusoidal Obstruction Syndrome by evaluating changes in tissue elasticity. ^{1 2 3 4 5}

Is ultrasound elastography safe for humans?

Ultrasound elastography, often using agents like SonoVue, is generally safe for humans. Serious adverse reactions are rare, and most side effects, such as headache or nausea, are minor and resolve on their own. ^{6 7 8 9 10}

How does ultrasound elastography differ from other treatments for sinusoidal obstruction syndrome?

Ultrasound elastography is unique because it is a non-invasive imaging technique that measures liver stiffness to help diagnose sinusoidal obstruction syndrome (SOS), unlike traditional methods that rely on clinical criteria and invasive procedures. This technique uses shear wave elastography (SWE) to detect changes in tissue elasticity, providing a rapid and reliable diagnosis, which is crucial for early intervention in SOS. ^{3 5 11 12 13}

Research Team

Sherwin Chan, MD PhD

Principal Investigator

Children's Mercy Hospital Kansas City

Eligibility Criteria

This trial is for patients undergoing intense pre-transplant treatment (myeloablative conditioning) for stem cell transplant, including those at high risk for liver-related complications post-transplant. It's not suitable for individuals who can't undergo ultrasound elastography due to conditions like an inability to remain still.

Inclusion Criteria

I am at high risk for severe organ damage due to my condition or recent treatments.

I am receiving sirolimus and tacrolimus to prevent graft-versus-host disease.

I am scheduled for a strong chemotherapy or radiation therapy before a stem cell transplant between April 1, 2019, and December 31, 2120.

Exclusion Criteria

You cannot stay still during a US SWE test.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2 weeks

1 visit (in-person)

Pre-conditioning

Ultrasound elastography performed within two weeks prior to starting conditioning regimen

2 weeks

1 visit (in-person)

Conditioning and Monitoring

Ultrasound elastography performed twice per week through Day +30 or discharge

4-6 weeks

8-12 visits (in-person)

Follow-up

Ultrasound elastography performed every 30 days until Day +100 or discharge

10 weeks

3 visits (in-person)

Treatment Details

Interventions

• Ultrasound Elastography

Trial Overview The study tests how well ultrasound elastography can predict and categorize the severity of a liver complication called Sinusoidal Obstruction Syndrome in bone marrow transplant patients. The goal is to establish a reliable method to identify patients' risks before severe symptoms develop.

Participant Groups

Group I: Patients Undergoing HCT Experimental Treatment 1 Intervention

All patients enrolled will undergo US SWE at specific time points as outlined in the protocol based on disease course.

Who Is Running the Clinical Trial?

Children's Mercy Hospital Kansas City

Lead Sponsor

Trials

261

Recruited

941,000+

Dana-Farber Cancer Institute

Collaborator

Trials

1,128

Recruited

382,000+

University of California, San Francisco

Collaborator

Trials

2,636

Recruited

19,080,000+

Duke University

Collaborator

Trials

2,495

Recruited

5,912,000+

University Hospitals Cleveland Medical Center

Collaborator

Trials

348

Recruited

394,000+

M.D. Anderson Cancer Center

Collaborator

Trials

3,107

Recruited

1,813,000+

Boston Children's Hospital

Collaborator

Trials

801

Recruited

5,584,000+

St. Jude Children's Research Hospital

Collaborator

Trials

451

Recruited

5,326,000+

Jazz Pharmaceuticals

Industry Sponsor

Trials

252

Recruited

35,100+

Bruce C. Cozadd

Jazz Pharmaceuticals

Chief Executive Officer since 2009

BA in Economics from Yale University, MBA from Stanford University

Dr. Austin

Jazz Pharmaceuticals

Chief Medical Officer since 2023

MD from the Royal College of Surgeons in Ireland

Nationwide Children's Hospital

Collaborator

Trials

354

Recruited

5,228,000+

Findings from Research

The 2D shear-wave elastography (2D-SWE) LOGIQ-S8 demonstrated good agreement with transient elastography in measuring liver stiffness in 348 patients with viral hepatitis or HIV, particularly showing strong correlation in those with hepatitis C or B infections.

2D-SWE showed excellent accuracy for identifying compensated-advanced chronic liver disease (c-ACLD), with optimal cut-off values of 6.4 kPa and 7.1 kPa for different severity levels, achieving high sensitivity (84% and 91%) and specificity (89% for both).

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Accuracy and concordance of two-dimensional shear-wave elastography using transient elastography as the reference in chronic viral hepatitis and HIV infection in Rio de Janeiro, Brazil. Coelho, M., Fernandes, F., Cardoso, SW., et al.[2023]

The study demonstrated excellent intraobserver reproducibility of shear wave elastography (SWE) measurements in the prostate, with an overall intraclass correlation coefficient (ICC) of 0.876 across 80 men with suspected prostate cancer.

Reproducibility varied by location within the prostate, being highest in the mid-gland area, indicating that operators should exercise caution and be aware of these differences when performing SWE measurements.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Shear wave elastography assessment in the prostate: an intraobserver reproducibility study. Woo, S., Kim, SY., Lee, MS., et al.[2018]

Shear wave elastography (SWE) and pulsed Doppler ultrasound both demonstrated similar diagnostic performance in distinguishing between benign and malignant breast lesions in a study of 79 patients.

SWE parameters, particularly Emax and Esd, showed significant correlations with pulsed Doppler parameters like the pulsatility index (PI) and resistive index (RI) in malignant lesions, suggesting a link between the mechanical and vascular properties of breast tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Shear wave elastography and pulsed doppler for breast lesions: Similar diagnostic performance and positively correlated stiffness and blood flow resistance. Jia, W., Yang, Z., Zhang, X., et al.[2022]

Ultrasound elastography (UE) is a promising non-invasive imaging technique for assessing intestinal changes in inflammatory bowel disease (IBD), particularly in detecting strictures in Crohn's disease patients, based on a systematic review of 12 studies.

UE may help differentiate between fibrosis and inflammation in the intestines, which is crucial for treatment decisions, but more research is needed to fully establish its role in IBD management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ultrasound Elastography in the Assessment of the Intestinal Changes in Inflammatory Bowel Disease-Systematic Review. Ślósarz, D., Poniewierka, E., Neubauer, K., et al.[2021]

Ultrasound elastography is a promising non-invasive imaging technique that assesses tissue stiffness, which can help diagnose various conditions, particularly liver fibrosis, and is gaining traction in imaging other organs like the breast and thyroid.

The technique is advantageous due to its wide availability, low cost, and ability to provide both qualitative and quantitative information about tissue mechanical properties, making it a valuable tool in clinical settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ultrasound Elastography: Review of Techniques and Clinical Applications. Sigrist, RMS., Liau, J., Kaffas, AE., et al.[2023]

In a study involving 23,188 abdominal examinations using the ultrasound contrast agent SonoVue, only 29 adverse events (AEs) were reported, indicating a very low incidence of complications.

The overall rate of serious adverse events was extremely low at 0.0086%, and SonoVue demonstrated a good safety profile, comparable to or better than other contrast agents used in radiology.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The safety of Sonovue in abdominal applications: retrospective analysis of 23188 investigations. Piscaglia, F., Bolondi, L.[2022]

In a review of over 201,000 administrations of ultrasound enhancement agents (UEAs), severe and critical adverse drug reactions (ADRs) were found to be more frequent with Lumason compared to Definity, with rates of 0.0848% for severe and 0.0330% for critical ADRs associated with Lumason.

The frequency of severe ADRs with Lumason has increased in recent years, and patients experiencing these reactions were more likely to have received a COVID-19 vaccination, particularly the Moderna vaccine, suggesting a potential link that requires further investigation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Incidence of Severe Adverse Drug Reactions to Ultrasound Enhancement Agents in a Contemporary Echocardiography Practice. Ali, MT., Johnson, M., Irwin, T., et al.[2023]

Ultrasound contrast agents are generally safe for clinical use, with serious adverse reactions being rare and most adverse events being minor and self-resolving, such as headache and nausea.

The Contrast Media Safety Committee found that while intolerance to some components can occur, generalized allergy-like reactions are infrequent, emphasizing the overall well-tolerated nature of these agents.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety of ultrasound contrast agents. Jakobsen, JA., Oyen, R., Thomsen, HS., et al.[2020]

In a study involving 34 pediatric patients with solid tumors, the intravenous administration of ultrasound contrast agents was found to be safe, with no significant changes in hemodynamic status observed during or after the procedure.

Only 2.2% of the procedures resulted in mild, transient side effects, such as taste alteration and tinnitus, which did not recur in subsequent examinations, indicating a favorable safety profile for these agents in children.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety of ultrasound contrast agents in the pediatric oncologic population: a single-institution experience. Coleman, JL., Navid, F., Furman, WL., et al.[2021]

Lumason® (SonoVue®) has been shown to be safe for use in special patient populations, including those with compromised cardiopulmonary conditions, with no significant adverse effects on cardiac or pulmonary function observed in studies involving patients with coronary artery disease, pulmonary hypertension, and chronic obstructive pulmonary disease.

A retrospective study of critically ill patients indicated that using Lumason® during echocardiography did not increase in-hospital mortality compared to echocardiography without the contrast agent, further supporting its safety profile in vulnerable populations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety of Lumason® (SonoVue®) in special populations and critically ill patients. Filippone, A., Kirchin, MA., Monteith, J., et al.[2023]

In a study of 63 adult patients undergoing hematopoietic stem cell transplantation, shear wave elastography (SWE) was evaluated as a non-invasive method for diagnosing hepatic sinusoidal obstruction syndrome (SOS)/veno-occlusive disease (VOD).

The technique successfully detected increased liver stiffness in all three patients who developed SOS/VOD, suggesting that SWE could be a valuable tool for early diagnosis of this life-threatening complication.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Shear Wave Elastography in the Detection of Sinusoidal Obstruction Syndrome in Adult Patients Undergoing Allogenic Hematopoietic Stem Cell Transplantation. Schulz, M., Vuong, LG., Müller, HP., et al.[2021]

Sinusoidal obstruction syndrome (SOS/VOD) is a serious complication that can occur after hematopoietic cell transplantation, requiring early diagnosis and intervention for better survival outcomes.

Current ultrasound techniques for diagnosing SOS/VOD need improvement in sensitivity and specificity, and innovative methods like Doppler ultrasound combined with shear wave elastography should be explored for better diagnostic accuracy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

New Ultrasound Techniques Challenge the Diagnosis of Sinusoidal Obstruction Syndrome. Dietrich, CF., Trenker, C., Fontanilla, T., et al.[2019]

Ultrasound elastography is a valuable diagnostic tool that measures tissue elasticity and can help diagnose conditions like liver fibrosis and cirrhosis, as well as suspicious lesions in organs such as the breast, prostate, and thyroid.

While it cannot yet replace standard diagnostic methods, elastography provides additional information that can enhance the overall diagnostic process.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Radiology Update Ultrasound Elastography – Quintessence for the Primary Care Physician]. Franckenberg, S., Gubler, C., Frauenfelder, T., et al.[2016]

References

1. England pubmed.ncbi.nlm.nih.gov

Accuracy and concordance of two-dimensional shear-wave elastography using transient elastography as the reference in chronic viral hepatitis and HIV infection in Rio de Janeiro, Brazil. [2023]

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

Shear wave elastography assessment in the prostate: an intraobserver reproducibility study. [2018]

3. Ireland pubmed.ncbi.nlm.nih.gov

Shear wave elastography and pulsed doppler for breast lesions: Similar diagnostic performance and positively correlated stiffness and blood flow resistance. [2022]

4. Switzerland pubmed.ncbi.nlm.nih.gov

Ultrasound Elastography in the Assessment of the Intestinal Changes in Inflammatory Bowel Disease-Systematic Review. [2021]

5. Australia pubmed.ncbi.nlm.nih.gov

Ultrasound Elastography: Review of Techniques and Clinical Applications. [2023]

6. England pubmed.ncbi.nlm.nih.gov

The safety of Sonovue in abdominal applications: retrospective analysis of 23188 investigations. [2022]

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

Incidence of Severe Adverse Drug Reactions to Ultrasound Enhancement Agents in a Contemporary Echocardiography Practice. [2023]

8. Germany pubmed.ncbi.nlm.nih.gov

Safety of ultrasound contrast agents. [2020]

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

Safety of ultrasound contrast agents in the pediatric oncologic population: a single-institution experience. [2021]

10. Switzerland pubmed.ncbi.nlm.nih.gov

Safety of Lumason® (SonoVue®) in special populations and critically ill patients. [2023]

11. Switzerland pubmed.ncbi.nlm.nih.gov

Shear Wave Elastography in the Detection of Sinusoidal Obstruction Syndrome in Adult Patients Undergoing Allogenic Hematopoietic Stem Cell Transplantation. [2021]

12. England pubmed.ncbi.nlm.nih.gov

New Ultrasound Techniques Challenge the Diagnosis of Sinusoidal Obstruction Syndrome. [2019]

13. Switzerland pubmed.ncbi.nlm.nih.gov

[Radiology Update Ultrasound Elastography – Quintessence for the Primary Care Physician]. [2016]