Genome Sequencing in the Intensive Care Unit Population

NCT04848090 | Enrolling By Invitation

• 1 other identifier: STUDY19050319
• Study Type: interventional
• Target: 400
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to understand how the use of whole genome sequencing (WGS) may be able to increase the speed with which a diagnosis is made for patients in an intensive care unit population. This is not an assessment of a new device, test, or technology. This project is an investigation of the utility of this technology in clinical care when compared to standard of care testing. The study will look at the ability to more quickly diagnose a patient (time to diagnosis and efficacy of testing) as compared to standard of care testing. The study will also look at the impact of WGS on patient outcomes and cost of clinical care.

Conditions

Infant, Newborn, Disease; Genetic Disease

Keywords

Whole Genome Sequencing; Whole Exome Analysis; Rapid Genetic Sequencing

Outcome Measures

Primary Outcomes (7)

• Confirmed Diagnosis

  Categorical Y/N confirmed diagnosis in the neonate participant detected with WGS, compared to results from standard of care (SOC) or as seen in the historical control (HC)

  Up to 4 years

• Diagnostic Rate

  Diagnostic rate with analysis via WGS, the 1722 neonatal specific gene filter, vs whole exome filter

  Up to 4 years

• Time to Diagnosis

  Time to diagnosis in days with WGS as compared to SOC testing or HC

  Up to 4 years

• Clinical Utility of WGS

  Clinical utility of WGS (e.g. changes in care management) compared to SOC or HC. Clinical utility is rated by a physician involved with case following the return of results using a Likert scale (1 - Not Useful at all, 2 - Not Very Useful, 3 - Neutral, 4 - Useful, 5 - Very Useful)

  Up to 4 years

• Care Cost Evaluation

  Total care cost in dollars in those receiving WGS as compared to HC

  Up to 4 years

• Length of Stay

  Total length of hospital stay in days in those receiving WGS as compared to HC

  Up to 4 years

• Need for Medical Utilization

  Number of major medical procedures, imaging studies, or consulting services encounters in subjects receiving WGS compared to those in HC

  Up to 4 years

Study Arms (1)

Neonate WGS Testing

OTHER

Neonate subjects who are eligible and whose parents consent to study will undergo blood sampling which will be sent for whole genome sequencing and bioinformatics analysis, filtering first a targeted panel of 1722 genes most likely to cause genetic disorders in the first year of life, and then with a whole exome filter if no obvious diagnosis is determined using the 1722 gene panel filter.

Diagnostic Test: Neonate WGS Testing

Interventions

Neonate WGS Testing DIAGNOSTIC_TEST

Neonates will undergo whole genome sequencing, and analysis with a targeted panel of genes likely to cause genetic disorders in the first year of life. If no diagnosis is identified, sequenced data will be analyzed using a whole exome filter. Performed in a CLIA-certified lab. Pathogenic, likely pathogenic, and VUS in genes related to the phenotype will be returned to the care team and family. Parents will be enrolled for the purpose of trio analysis with the child to assist in determining the pathogenicity of variants in genomic sequencing. Pathogenic and likely-pathogenic findings will be reported to the parents in the setting of genetic counseling. Sibling will be enrolled and have samples collected for use in the genetic analysis only if deemed essential. Results will be reported to the parents in the setting of genetic counseling.

Neonate WGS Testing

Eligibility Criteria

• Age: Up to 1 Year
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Neonates: In order to be approached to participate, a neonate must meet all of the following criteria:
• Greater than 24 weeks gestational age
• Birth weight greater than 600 grams
• Admitted to the intensive care unit at UPMC Children's Hospital (CHP) and/or Magee Women's Hospital
• Possibility of a genetic disorder based on signs, symptoms, and laboratory values triggering a formal clinical medical genetics consult by the clinical care team.
• Triaged by PI or attending co-investigators and prioritized to introduction of this research study based on patient-specific clinical concerns
• Documented informed consent from parent/guardian
• Historical Controls: Individuals who have been evaluated by Medical Genetics within the last 24 months and who meet the criteria for matched controls as defined by propensity score matching.

You may not qualify if:

• Neonates: An individual who meets any of the following criteria will be excluded from participating in this study:
• Has a known etiologic diagnosis (e.g. prenatal testing)
• Has a major congenital anomaly (renal, cardiac, hepatic, neurological, or pulmonary malformations) associated with a chromosomal anomaly detected on prenatal testing (e.g. ultrasound, genetic testing)
• Sequencing sent after birth for any other reason than the genetics consult that triggers the study
• Presence of documented significant congenital infection (e.g. congenital cytomegalovirus)
• Parents:
• Is not the biological parent of the identified neonate
• Having had previous genetic testing does not exclude the parent from participating in this study.
• Siblings:
• Is not require for accurate interpretation of neonate results
• Having had previous genetic testing does not exclude the sibling from participating in this study.
• Historical Control: Has not been seen within the past 24 months and/or does not meet the criteria for matched control as defined by propensity score matching. Part of this matching requires that the historical control be matched to a study participant based on age, thus they will be selected based on all matching criteria and will be excluded if they do not meet the criteria, including age.

Sponsors & Collaborators

• Jerry Vockley, MD, PhD: lead

Study Sites (1)

UPMC Children's Hospital of Pittsburgh

Pittsburgh, Pennsylvania, 15224, United States

Location

MeSH Terms

Conditions

Disease; Genetic Diseases, Inborn

Condition Hierarchy (Ancestors)

Pathologic Processes; Pathological Conditions, Signs and Symptoms; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Study Officials

• Gerard Vockley, MD, PhD

  University of Pittsburgh

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor

Model Details: This is an observational study to understand if the use of whole genome sequencing (WGS) increases the speed to diagnosis and how clinical management is changed in an intensive care population of neonates. Participants will include 100 neonates and their parents for trio analysis, for up to 300 individuals for whom consent is obtained testing will be completed. Participants will also include 100 matched historical controls.

Study Record Dates

• First Submitted: April 13, 2021
• First Posted: April 19, 2021
• Study Start: July 13, 2020
• Primary Completion (Estimated): February 1, 2027
• Study Completion (Estimated): June 1, 2027
• Last Updated: January 9, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)