Back to resultsNICUSeq: 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)
Primary Purpose
Rare Diseases
Status
Completed
Phase
Not Applicable
Locations
United States
Study Type
Interventional
Intervention
clinical whole genome sequencing (cWGS)
Sponsored by
About this trial
This is an interventional other trial for Rare Diseases focused on measuring ICU, Intensive Care Unit
Eligibility 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.
Sites / Locations
- Rady's/Children's Hospital of Orange County
- Washington University in St. Louis School of Medicine & St. Louis Children's Hospital
- University of Nebraska Medical Center & Children's Hospital
- Children's Hospital of Philadelpia
- LeBonheur Hospital
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
No Intervention
Arm Label
15 day cWGS and Standard of Care
Standard of Care
Arm Description
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).
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 Outcome Measures
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.
Secondary Outcome Measures
Diagnostic Yield
Diagnostic yield (# positive diagnoses/ total # of each proband expressed as a percentage)
Diagnostic Accuracy
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
Genetic Results Returned
% diagnoses returned before discharge or death
Costs
Pre-test costs of hospital care
Average Time to Diagnosis
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
The amount of imaging tests ordered as assessed by counting the number of tests per cohort.
Clinical services utilization includes the number of imaging tests ordered.
cWGS satisfaction questionnaire will be given to clinicians and families at the conclusion of the study.
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.
Assessment of Clinical Utility by using a questionnaire
A questionnaire developed by the study team will assess the Clinical Utility of the cWGS test
Change in Care Setting from the ICU environment
Changes in care level setting from the ICU environment will be compared between the 15 day cWGS group and the SOC group.
Time to diagnosis
Time to diagnosis (in days of life)
Full Information
NCT ID
NCT03290469
First Posted
September 13, 2017
Last Updated
November 16, 2020
Sponsor
Illumina, Inc.
Collaborators
Le Bonheur Children's Hospital, Rady Pediatric Genomics & Systems Medicine Institute, Children's Hospital of Orange County, Children's Hospital and Medical Center, Omaha, Nebraska, St. Louis Children's Hospital, Children's Hospital of Philadelphia
1. Study Identification
Unique Protocol Identification Number
NCT03290469
Brief Title
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
Acronym
NICU-Seq
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
2. Study Status
Record Verification Date
May 2019
Overall Recruitment Status
Completed
Study Start Date
September 14, 2017 (Actual)
Primary Completion Date
April 30, 2019 (Actual)
Study Completion Date
January 13, 2020 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Illumina, Inc.
Collaborators
Le Bonheur Children's Hospital, Rady Pediatric Genomics & Systems Medicine Institute, Children's Hospital of Orange County, Children's Hospital and Medical Center, Omaha, Nebraska, St. Louis Children's Hospital, Children's Hospital of Philadelphia
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Rare Diseases
Keywords
ICU, Intensive Care Unit
7. Study Design
Primary Purpose
Other
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
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
ParticipantCare ProviderInvestigator
Masking Description
All investigators are masked to the study arm until Day 15 to ensure SOC throughout first 15 days on study.
Allocation
Randomized
Enrollment
355 (Actual)
8. Arms, Groups, and Interventions
Arm Title
15 day cWGS and Standard of Care
Arm Type
Experimental
Arm Description
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).
Arm Title
Standard of Care
Arm Type
No Intervention
Arm Description
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).
Intervention Type
Other
Intervention Name(s)
clinical whole genome sequencing (cWGS)
Intervention Description
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.
Primary Outcome Measure Information:
Title
A difference in Change of Management between the 15 day cWGS and standard of care groups
Description
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.
Time Frame
Day 60
Secondary Outcome Measure Information:
Title
Diagnostic Yield
Description
Diagnostic yield (# positive diagnoses/ total # of each proband expressed as a percentage)
Time Frame
90 Days
Title
Diagnostic Accuracy
Description
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
Time Frame
90 Days
Title
Genetic Results Returned
Description
% diagnoses returned before discharge or death
Time Frame
90 Days
Title
Costs
Description
Pre-test costs of hospital care
Time Frame
90 Days
Title
Average Time to Diagnosis
Description
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
Time Frame
90 Days
Title
The amount of imaging tests ordered as assessed by counting the number of tests per cohort.
Description
Clinical services utilization includes the number of imaging tests ordered.
Time Frame
90 Days
Title
cWGS satisfaction questionnaire will be given to clinicians and families at the conclusion of the study.
Description
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.
Time Frame
90 Days
Title
Assessment of Clinical Utility by using a questionnaire
Description
A questionnaire developed by the study team will assess the Clinical Utility of the cWGS test
Time Frame
90 Days
Title
Change in Care Setting from the ICU environment
Description
Changes in care level setting from the ICU environment will be compared between the 15 day cWGS group and the SOC group.
Time Frame
90 Days
Title
Time to diagnosis
Description
Time to diagnosis (in days of life)
Time Frame
90 Days
10. Eligibility
Sex
All
Minimum Age & Unit of Time
1 Day
Maximum Age & Unit of Time
120 Days
Accepts Healthy Volunteers
No
Eligibility 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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Ryan J. Taft, PhD
Organizational Affiliation
Illumina, Inc.
Official's Role
Study Director
Facility Information:
Facility Name
Rady's/Children's Hospital of Orange County
City
Orange
State/Province
California
ZIP/Postal Code
92868
Country
United States
Facility Name
Washington University in St. Louis School of Medicine & St. Louis Children's Hospital
City
Saint Louis
State/Province
Missouri
ZIP/Postal Code
63110
Country
United States
Facility Name
University of Nebraska Medical Center & Children's Hospital
City
Omaha
State/Province
Nebraska
ZIP/Postal Code
68114
Country
United States
Facility Name
Children's Hospital of Philadelpia
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19104
Country
United States
Facility Name
LeBonheur Hospital
City
Memphis
State/Province
Tennessee
ZIP/Postal Code
38103
Country
United States
12. IPD Sharing Statement
Plan to Share IPD
No
IPD Sharing 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.
Citations:
PubMed Identifier
34570182
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. Erratum In: JAMA Pediatr. 2021 Dec 1;175(12):1295.
Results Reference
derived
Learn more about this trial
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
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