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

NCT ID: NCT03290469

Last Updated: 2020-11-18

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 355 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-09-14
• Study Completion Date: 2020-01-13

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.

Conditions

Rare Diseases

Keywords

ICU; Intensive Care Unit

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: OTHER
• Blinding Strategy: TRIPLE

Study Groups

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).

Group Type: EXPERIMENTAL

clinical whole genome sequencing (cWGS)

Intervention Type: 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.

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).

Group Type: NO_INTERVENTION

No interventions assigned to this group

Interventions

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.

Intervention Type: OTHER

Eligibility Criteria

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

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.

• Minimum Eligible Age: 1 Day
• Maximum Eligible Age: 120 Days
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Le Bonheur Children's Hospital

OTHER

Sponsor Role: collaborator

Rady Pediatric Genomics & Systems Medicine Institute

OTHER

Sponsor Role: collaborator

Children's Hospital of Orange County

OTHER

Sponsor Role: collaborator

Children's Hospital and Medical Center, Omaha, Nebraska

OTHER

Sponsor Role: collaborator

St. Louis Children's Hospital

OTHER

Sponsor Role: collaborator

Children's Hospital of Philadelphia

OTHER

Sponsor Role: collaborator

Illumina, Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Ryan J. Taft, PhD

Role: STUDY_DIRECTOR

Illumina, Inc.

Locations

Rady's/Children's Hospital of Orange County

Orange, California, United States

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

St Louis, Missouri, United States

University of Nebraska Medical Center & Children's Hospital

Omaha, Nebraska, United States

Children's Hospital of Philadelpia

Philadelphia, Pennsylvania, United States

LeBonheur Hospital

Memphis, Tennessee, United States

Countries

United States

References

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.

Reference Type: DERIVED

PMID: 34570182 (View on PubMed)

Other Identifiers

NICU-R001

Identifier Type: -

Identifier Source: org_study_id