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Validating Ultrasound Biomarkers for Hepatic Sinusoidal Obstruction Syndrome in Pediatric Hematopoietic Cell Transplant Patients

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ClinicalTrials.gov Identifier: NCT03963999
Recruitment Status : Withdrawn (We did not receive grant funding. We will reapply in June of 2020)
First Posted : May 28, 2019
Last Update Posted : January 13, 2020
Sponsor:
Collaborators:
Nationwide Children's Hospital
St. Jude Children's Research Hospital
Children's Hospital Colorado
Information provided by (Responsible Party):
Children's Mercy Hospital Kansas City

Brief Summary:
Hepatic veno-occlusive disease/sinusoidal obstructive syndrome (VOD/SOS) is a potentially fatal complication of hematopoietic cell transplant (HCT). Historically VOD/SOS has been clinically diagnosed using the modified Seattle criteria or the Baltimore criteria. The modified Seattle Criteria define VOD/SOS diagnosis is made when two of the following three criteria are present in a patient within 21 days of transplantation: hyperbilirubinemia (total serum bilirubin > 2 mg/dL), hepatomegaly or right upper quadrant liver pain, and weight gain (> 2% of baseline) or ascites. Other conditions like graft versus host disease, sepsis syndrome (fever and hypotension), cardiac failure, or tumor infiltration) have to be excluded. This definition was from a well-designed retrospective cohort study on 255 adult and pediatric HCT patients in which the VOD/SOS incidence was 21%. McDonald et al followed up this work with a prospective cohort study of 355 patients noting an incidence of VOD/SOS of 54%. These seminal studies have had a major impact on the field by defining clinical diagnostic criteria. An alternative diagnostic criteria (Baltimore criteria) was proposed by Jones et al as a part of a well-designed retrospective review of 235 HCT patients finding a VOD/SOS incidence of 22%. Jones defined VOD/SOS as the presence of hyperbilirubinemia (total serum bilirubin > 2 mg/dL) along with at least 2 of 3 other findings: hepatomegaly, ascites, and weight gain (> 5% of baseline).

Condition or disease Intervention/treatment Phase
Sinusoidal Obstruction Syndrome Veno Occlusive Disease, Hepatic Bone Marrow Transplant Complications Stem Cell Transplant Complications Diagnostic Test: Ultrasound Elastography Drug: Contrast Enhanced Ultrasound (CEUS) Phase 4

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 0 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Intervention Model Description: All patients undergoing myeloblative conditioning regimen as part of hematopoietic cell transplant or prior liver damage or other high risk factor will be consecutively studied
Masking: None (Open Label)
Primary Purpose: Diagnostic
Official Title: Validating Ultrasound Biomarkers for Hepatic Sinusoidal Obstruction Syndrome in Pediatric Hematopoietic Cell Transplant Patients
Estimated Study Start Date : April 1, 2020
Estimated Primary Completion Date : April 30, 2024
Estimated Study Completion Date : April 1, 2025

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Ultrasound

Arm Intervention/treatment
Experimental: Patients Undergoing HCT
All patients enrolled will undergo grayscale US, Doppler US, US SWE and CEUS at specific time points as outlined in the protocol based on disease course.
Diagnostic Test: Ultrasound Elastography
Ultrasound shear wave elastography

Drug: Contrast Enhanced Ultrasound (CEUS)
Contrast-enhanced ultrasound (CEUS) uses an intravenous injection of microbubble contrast agent.
Other Name: Lumason (sulfur hexafluoride lipid-type A microspheres)




Primary Outcome Measures :
  1. Define Sensitivity and Specificity of US (grayscale, Doppler and SWE) for Diagnosis and Severity Grading for SOS/VOD [ Time Frame: 100 days post transplant ]
    Determine the sensitivity and specificity of US for diagnosis and severity grading of VOD/SOS in a cohort of 250 pediatric HCT patients.

  2. Define Sensitivity and Specificity of CEUS for Diagnosis and Severity Grading for SOS/VOD [ Time Frame: 100 days post transplant ]
    Determine the sensitivity and specificity of contrast enhanced ultrasound (CEUS) variables for diagnosis and severity grading of VOD/SOS as compared to the pediatric EBMT criteria.

  3. Define Optimal Timing for US for Early Diagnosis and Risk Stratification of VOD/SOS [ Time Frame: 100 days post transplant ]
    Determine the optimal timing for ultrasound measurements to help predict early diagnosis and risk stratification of VOD/SOS.



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Ages Eligible for Study:   1 Month to 25 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • HCT patient under 25 years of age with
  • myeloablative conditioning,
  • prior liver damage or
  • other high risk factor:
  • Neuroblastoma,
  • HLH,
  • Osteopetrosis,
  • Thalassemia,
  • Treatment with inotuzumab or gemtuzumab within 3 months prior to HCT admission,
  • Hepatic iron overload,
  • Steatohepatitis,
  • Active inflammatory or infection hepatitis or
  • Any other condition which puts the patient at a higher risk of developing VOD).

Exclusion Criteria:

  • Any patient who has contraindication to any of the ultrasound procedures (e.g. unable to hold still).

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03963999


Locations
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United States, Missouri
Children's Mercy Hospital
Kansas City, Missouri, United States, 64108
Sponsors and Collaborators
Children's Mercy Hospital Kansas City
Nationwide Children's Hospital
St. Jude Children's Research Hospital
Children's Hospital Colorado
Investigators
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Principal Investigator: Sherwin S Chan, MD, PhD Children's Mercy Hospital Kansas City
Publications:

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Responsible Party: Children's Mercy Hospital Kansas City
ClinicalTrials.gov Identifier: NCT03963999    
Other Study ID Numbers: STUDY00000792
First Posted: May 28, 2019    Key Record Dates
Last Update Posted: January 13, 2020
Last Verified: January 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
Keywords provided by Children's Mercy Hospital Kansas City:
Ultrasound Elastography
Additional relevant MeSH terms:
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Hepatic Veno-Occlusive Disease
Syndrome
Disease
Pathologic Processes
Liver Diseases
Digestive System Diseases
Vascular Diseases
Cardiovascular Diseases