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NICUSeq: A Trial to Evaluate the Clinical Utility of Human Whole Genome Sequencing (WGS) Compared to Standard of Care in Acute Care Neonates and Infants (NICU-Seq)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03290469
Recruitment Status : Active, not recruiting
First Posted : September 25, 2017
Last Update Posted : May 13, 2019
Sponsor:
Collaborators:
Le Bonheur Children's Hospital
Rady Pediatric Genomics & Systems Medicine Institute
Children’s Hospital of Orange County
Children's Hospital of Omaha
St. Louis Children's Hospital
Children's Hospital of Philadelphia
Information provided by (Responsible Party):
Illumina, Inc.

Brief Summary:
Prospective, multi-site, study to evaluate the clinical utility of cWGS in a proband. One group will receive cWGS and a clinical report approximately 15 days after blood samples are received, while the other group will continue to receive standard of care until Day 60. The standard of care group will receive cWGS and a clinical report at Day 60 as part of secondary and tertiary analyses. Both groups will be followed for a total of 90 days.

Condition or disease Intervention/treatment Phase
Rare Diseases Other: clinical whole genome sequencing (cWGS) Not Applicable

Detailed Description:
This is a prospective, multi-site, randomized study to evaluate the clinical utility of cWGS in each proband. Throughout this study, each proband will receive SOC testing as determined by the site clinical team. Upon enrollment in the study, each proband will be randomly assigned to the 15 day cWGS group or the SOC group. SOC is defined as the management of the proband's care under the same or similar conditions as if the proband was not enrolled in this study. A blood sample from each enrolled proband will be collected and shipped to the Illumina Clinical Services Laboratory ("ICSL"), which is Clinical Laboratory Improvement Amendments (CLIA)-certified and College of American Pathologists (CAP)-accredited. ICSL will conduct cWGS testing with the TruGenome Undiagnosed Disease Test ("TruGenome Test"). The TruGenome Test cWGS results will be provided to the Principal Investigator (PI) or designee who will evaluate each proband test outcome based on the aggregate medical information, informed by the cWGS or SOC results.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 355 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: Multi-cohort, time delay study receiving Clinical Whole Genome Sequencing (cWGS) at either 15 days or 60 days in an acutely ill newborn population
Masking: Triple (Participant, Care Provider, Investigator)
Masking Description: All investigators are masked to the study arm until Day 15 to ensure SOC throughout first 15 days on study.
Primary Purpose: Other
Official Title: NICUSeq: A Prospective Trial to Evaluate the Clinical Utility of Human Whole Genome Sequencing (WGS) Compared to Standard of Care in Acute Care Neonates and Infants
Actual Study Start Date : August 31, 2017
Actual Primary Completion Date : April 30, 2019
Estimated Study Completion Date : July 31, 2019

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Rare Diseases

Arm Intervention/treatment
Experimental: 15 day cWGS and Standard of Care
Enrolled cohorts receive the results of the clinical whole genome sequencing (cWGS) after 15 days of the sample receipt while still undergoing standard of care (SOC).
Other: clinical whole genome sequencing (cWGS)
Clinical Whole Genome Sequencing (cWGS) consists of the sequencing, analysis and interpretation of subjects samples and a return of the result to the ordering physician.

No Intervention: Standard of Care
Enrolled cohorts receive the results of the clinical whole genome sequencing (cWGS) after 60 days of the sample receipt while still undergoing standard of care (SOC).



Primary Outcome Measures :
  1. A difference in Change of Management between the 15 day cWGS and standard of care groups [ Time Frame: Day 60 ]

    Change of Management is a binary (yes or no) based on assignments made by the PI or designee at each site using the following domains:

    • Condition specific management
    • Condition specific supportive interventions
    • Palliative care/End of Life Care A change in any of these domains will be considered a change of management.


Secondary Outcome Measures :
  1. Diagnostic Yield [ Time Frame: 90 Days ]
    Diagnostic yield (# positive diagnoses/ total # of each proband expressed as a percentage)

  2. Diagnostic Accuracy [ Time Frame: 90 Days ]

    Diagnostic accuracy (percent positive agreement between test outcome classified by the medical monitor and the site PI or designee)

    % diagnoses returned before discharge or death


  3. Genetic Results Returned [ Time Frame: 90 Days ]
    % diagnoses returned before discharge or death

  4. Costs [ Time Frame: 90 Days ]
    Pre-test costs of hospital care

  5. Average Time to Diagnosis [ Time Frame: 90 Days ]
    Average time (in days) to diagnose between cWGS and SOC based on the comparison of the (a) cWGS results and the (b) current clinical diagnoses

  6. The amount of imaging tests ordered as assessed by counting the number of tests per cohort. [ Time Frame: 90 Days ]
    Clinical services utilization includes the number of imaging tests ordered.

  7. cWGS satisfaction questionnaire will be given to clinicians and families at the conclusion of the study. [ Time Frame: 90 Days ]
    The questionnaire is a likard scale questionnaire developed by the study team to assess satisfaction levels from the perspective of the clinician and also the parent.

  8. Assessment of Clinical Utility by using a questionnaire [ Time Frame: 90 Days ]
    A questionnaire developed by the study team will assess the Clinical Utility of the cWGS test

  9. Change in Care Setting from the ICU environment [ Time Frame: 90 Days ]
    Changes in care level setting from the ICU environment will be compared between the 15 day cWGS group and the SOC group.

  10. Time to diagnosis [ Time Frame: 90 Days ]
    Time to diagnosis (in days of life)



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   up to 120 Days   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Proband Inclusion Criteria

  1. Current admission in a Neonatal Intensive Care Unit/Intensive Care Unit at a participating clinical site at the time of enrollment from day of life 0 to 120 days
  2. A suspected genetic etiology of disease, based on objective clinical findings or other phenotypic defects for which a genetic test would be considered
  3. Must be able to have 1 - 1.25 ml tube of whole blood drawn for testing
  4. One parent of the proband must be able to provide written informed consent
  5. At least one biological parent must agree to participate and provide at least 4 ml of whole blood for testing

Exclusion Criteria:

Proband Exclusion Criteria

  1. Known non-genetic cause(s) of disease, disorder, or phenotypic defect
  2. The phenotype is fully explained by complications of prematurity
  3. Trisomy 13, 18 or 21 or Turner Syndrome is the likely diagnosis; such a proband will be eligible if a diagnostic karyotype is normal
  4. Blood transfusion within 48 hours (each proband will be re-eligible 48 hours after the most recent transfusion)
  5. The PI decides that the study is not in the best interest of the proband (for example, the neonate or infant is at a high risk of severe morbidity or mortality within the next 7 days and these risks could be mitigated by alternative testing). Subsequent eligibility for enrollment of each proband is at the discretion of the site PI.

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): NCT03290469


Locations
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United States, California
Rady's/Children's Hospital of Orange County
Orange, California, United States, 92868
United States, Missouri
Washington University in St. Louis School of Medicine & St. Louis Children's Hospital
Saint Louis, Missouri, United States, 63110
United States, Nebraska
University of Nebraska Medical Center & Children's Hospital
Omaha, Nebraska, United States, 68114
United States, Pennsylvania
Children's Hospital of Philadelpia
Philadelphia, Pennsylvania, United States, 19104
United States, Tennessee
LeBonheur Hospital
Memphis, Tennessee, United States, 38103
Sponsors and Collaborators
Illumina, Inc.
Le Bonheur Children's Hospital
Rady Pediatric Genomics & Systems Medicine Institute
Children’s Hospital of Orange County
Children's Hospital of Omaha
St. Louis Children's Hospital
Children's Hospital of Philadelphia
Investigators
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Study Director: Ryan J. Taft, PhD Illumina, Inc.

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Responsible Party: Illumina, Inc.
ClinicalTrials.gov Identifier: NCT03290469    
Other Study ID Numbers: NICU-R001
First Posted: September 25, 2017    Key Record Dates
Last Update Posted: May 13, 2019
Last Verified: May 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Plan Description: Deidentified and curated variant and limited phenotype information will be submitted to ClinVar. ClinVar is a freely accessible, public archive of reports of the relationships among human variations and phenotypes hosted by the National Center for Biotechnology Information (NCBI) and funded by Intramural National Institutes of Health (NIH) funding. No personal health information (PHI) or information identifying the participant or family will be submitted.

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Illumina, Inc.:
ICU
Intensive Care Unit
Additional relevant MeSH terms:
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Rare Diseases
Disease Attributes
Pathologic Processes