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
Trial Snapshot
- Phase
- Not Applicable
- Status
- Completed
- Sponsor
- Illumina, Inc.
- Enrollment
- 355
- Locations
- 5
- Primary Endpoint
- A difference in Change of Management between the 15 day cWGS and standard of care groups
Study Overview
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.
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.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Other
- 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.
Eligibility Criteria
- Ages
- 1 Day to 120 Days (Child)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Proband Inclusion Criteria
- •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
- •A suspected genetic etiology of disease, based on objective clinical findings or other phenotypic defects for which a genetic test would be considered
- •Must be able to have 1 - 1.25 ml tube of whole blood drawn for testing
- •One parent of the proband must be able to provide written informed consent
- •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
- •Known non-genetic cause(s) of disease, disorder, or phenotypic defect
- •The phenotype is fully explained by complications of prematurity
- •Trisomy 13, 18 or 21 or Turner Syndrome is the likely diagnosis; such a proband will be eligible if a diagnostic karyotype is normal
- •Blood transfusion within 48 hours (each proband will be re-eligible 48 hours after the most recent transfusion)
- •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.
Arms & Interventions
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).
Intervention: clinical whole genome sequencing (cWGS) (Other)
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).
Outcomes
Primary Outcomes
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 Outcomes
- Diagnostic Yield(90 Days)
- cWGS satisfaction questionnaire will be given to clinicians and families at the conclusion of the study.(90 Days)
- Diagnostic Accuracy(90 Days)
- Average Time to Diagnosis(90 Days)
- Change in Care Setting from the ICU environment(90 Days)
- Genetic Results Returned(90 Days)
- Costs(90 Days)
- Time to diagnosis(90 Days)
- The amount of imaging tests ordered as assessed by counting the number of tests per cohort.(90 Days)
- Assessment of Clinical Utility by using a questionnaire(90 Days)