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

NCT03290469 | Completed

• 1 other identifier: NICU-R001
• Study Type: interventional
• Target: 355
• Locations: 1 country
• Sites: 5

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.

Conditions

Rare Diseases

Keywords

ICU; Intensive Care Unit

Outcome Measures

Primary Outcomes (1)

• A difference in Change of Management between the 15 day cWGS and standard of care groups

  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.

  Day 60

Secondary Outcomes (10)

• Diagnostic Yield

  90 Days

• Diagnostic Accuracy

  90 Days

• Genetic Results Returned

  90 Days

• Costs

  90 Days

• Average Time to Diagnosis

  90 Days

Study Arms (2)

15 day cWGS and Standard of Care

EXPERIMENTAL

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)

Standard of Care

NO INTERVENTION

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).

Interventions

clinical whole genome sequencing (cWGS) OTHER

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.

15 day cWGS and Standard of Care

Eligibility Criteria

• Age: 1 Day - 120 Days
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Illumina, Inc.: lead
• Le Bonheur Children's Hospital: collaborator
• Rady Pediatric Genomics & Systems Medicine Institute: collaborator
• Children's Hospital of Orange County: collaborator
• Children's Hospital and Medical Center, Omaha, Nebraska: collaborator
• St. Louis Children's Hospital: collaborator
• Children's Hospital of Philadelphia: collaborator

Study Sites (5)

Rady's/Children's Hospital of Orange County

Orange, California, 92868, United States

Location

Washington University in St. Louis School of Medicine & St. Louis Children's Hospital

St Louis, Missouri, 63110, United States

Location

University of Nebraska Medical Center & Children's Hospital

Omaha, Nebraska, 68114, United States

Location

Children's Hospital of Philadelpia

Philadelphia, Pennsylvania, 19104, United States

Location

LeBonheur Hospital

Memphis, Tennessee, 38103, United States

Location

Related Publications (1)

• 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.

  PMID: 34570182 DERIVED

MeSH Terms

Conditions

Rare Diseases

Condition Hierarchy (Ancestors)

Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Ryan J. Taft, PhD

  Illumina, Inc.

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Masking Details: All investigators are masked to the study arm until Day 15 to ensure SOC throughout first 15 days on study.
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Multi-cohort, time delay study receiving Clinical Whole Genome Sequencing (cWGS) at either 15 days or 60 days in an acutely ill newborn population

Study Record Dates

• First Submitted: September 13, 2017
• First Posted: September 25, 2017
• Study Start: September 14, 2017
• Primary Completion: April 30, 2019
• Study Completion: January 13, 2020
• Last Updated: November 18, 2020

Record last verified: 2019-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (5)