Clinical trial NCT03290469: 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
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Rare Diseases
Keywords: ICU
Intensive Care Unit
Lead sponsor: Illumina, Inc.
Sponsor class: INDUSTRY
Collaborators: name: Le Bonheur Children's Hospital
name: Rady Pediatric Genomics & Systems Medicine Institute
name: Children's Hospital of Orange County
name: Children's Hospital and Medical Center, Omaha, Nebraska
name: St. Louis Children's Hospital
name: Children's Hospital of Philadelphia
First posted: 2017-09-25
Enrollment: 355
Sex: ALL
Minimum age (years): 1
Maximum age (years): 120
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
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
Primary purpose: OTHER

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.

Eligibility 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.

Primary outcomes:
measure: A difference in Change of Management between the 15 day cWGS and standard of care groups
timeFrame: Day 60
Secondary outcomes:
measure: Diagnostic Yield
timeFrame: 90 Days
measure: Diagnostic Accuracy
timeFrame: 90 Days
measure: Genetic Results Returned
timeFrame: 90 Days
measure: Costs
timeFrame: 90 Days
measure: Average Time to Diagnosis
timeFrame: 90 Days
measure: The amount of imaging tests ordered as assessed by counting the number of tests per cohort.
timeFrame: 90 Days
measure: cWGS satisfaction questionnaire will be given to clinicians and families at the conclusion of the study.
timeFrame: 90 Days
measure: Assessment of Clinical Utility by using a questionnaire
timeFrame: 90 Days
measure: Change in Care Setting from the ICU environment
timeFrame: 90 Days
measure: Time to diagnosis
timeFrame: 90 Days
Other outcomes:
Locations:
city: Orange
country: United States
facility: Rady's/Children's Hospital of Orange County
state: California
city: Saint Louis
country: United States
facility: Washington University in St. Louis School of Medicine & St. Louis Children's Hospital
state: Missouri
city: Omaha
country: United States
facility: University of Nebraska Medical Center & Children's Hospital
state: Nebraska
city: Philadelphia
country: United States
facility: Children's Hospital of Philadelpia
state: Pennsylvania
city: Memphis
country: United States
facility: LeBonheur Hospital
state: Tennessee
Study officials:
affiliation: Illumina, Inc.
name: Ryan J. Taft, PhD
role: STUDY_DIRECTOR
References:
citation: NICUSeq Study Group; Krantz ID, Medne L, Weatherly JM, Wild KT, Biswas S, Devkota B, Hartman T, Brunelli L, Fishler KP, Abdul-Rahman O, Euteneuer JC, Hoover D, Dimmock D, Cleary J, Farnaes L, Knight J, Schwarz AJ, Vargas-Shiraishi OM, Wigby K, Zadeh N, Shinawi M, Wambach JA, Baldridge D, Cole FS, Wegner DJ, Urraca N, Holtrop S, Mostafavi R, Mroczkowski HJ, Pivnick EK, Ward JC, Talati A, Brown CW, Belmont JW, Ortega JL, Robinson KD, Brocklehurst WT, Perry DL, Ajay SS, Hagelstrom RT, Bennett M, Rajan V, Taft RJ. Effect of Whole-Genome Sequencing on the Clinical Management of Acutely Ill Infants With Suspected Genetic Disease: A Randomized Clinical Trial. JAMA Pediatr. 2021 Dec 1;175(12):1218-1226. doi: 10.1001/jamapediatrics.2021.3496.