Prenatal Precision Medicine (NSIGHT2): A Randomized, Blinded, Prospective Study of the Clinical Utility of Rapid Genomic Sequencing for Infants in the Acute-care Setting

161983

This study will seek to determine if rapid genomic sequencing improves outcomes for acutely ill infants. The investigator will enroll up to 1,000 acutely ill infants in a prospective, randomized, blinded study to either rapid Whole Genome Sequencing (WGS) or rapid Whole Exome Sequencing (WES, which is 2% of the genome and \~4-fold less expensive). 213 infants were actually enrolled. Outcomes will be measured both by objective clinical measures and family perceptions (patient/family centered outcomes). Primary analysis of WGS or WES will be in infants alone. Secondary analysis, in infants who do not receive a diagnosis, will be of families - ideally trios (mother, father, and affected infant), which is \~2-fold more expensive. Trios will be analyzed within the same randomization arm (WGS or WES). This study is designed to quantify which acutely ill infants benefit from rapid genomic sequencing, by how much they benefit, how they benefit, which rapid genomic sequencing method is superior, and the cost effectiveness of such testing.

2017-06-29

2018-10-09

2024-07-30

Active (not recruiting)

213

Inclusion Criteria: Individual in whom one of the following criteria is met: 1. Acutely ill inpatient of less than 4 months of age and within 96 hours of admission. 2. Acutely ill inpatient of less than 4 months of age and within 96 hours of development of an abnormal response to standard therapy for an underlying condition. 3. Acutely ill inpatient of less than 4 months of age and within 96 hours of development of clinical feature or laboratory test value suggestive of a genetic condition. 4. Biological relative of an infant enrolled in this study. Exclusion Criteria: Inpatients of greater than 4 months of age, or who do not meet any of the inclusion criteria, or with: 1. Neonatal infection or sepsis with normal response to therapy 2. Isolated prematurity 3. Isolated unconjugated hyperbilirubinemia 4. Hypoxic Ischemic Encephalopathy with clear precipitating event 5. Previously confirmed genetic diagnosis that explains their clinical condition (i.e. have a positive genetic test) 6. Isolated Transient Neonatal Tachypnea 7. Permission is unable to be obtained by a legal guardian or court-appointed representative within 96 hours of becoming eligible for enrollment. 8. Non-viable neonates - newborns less than 28 days of life with a modified code status (only full code patients may be enrolled).

{'studyType': 'INTERVENTIONAL', 'phases': ['NA'], 'designInfo': {'allocation': 'RANDOMIZED', 'interventionModel': 'PARALLEL', 'interventionModelDescription': "The initial symptom-driven analysis will be conducted on the patient's (NICU infants) sample only (singleton analysis). Patients will be randomized to receive either whole genome sequencing or whole exome sequencing. If a diagnosis is not found promptly (within 24 hours) via singleton analysis, sequential analysis of the family (or any combination of parents and/or other family members) will be analyzed using the same technology that the patient was randomized to receive.\n\nThe study includes parental and physician questionnaires to understand perceptions regarding testing. There is no randomization of parents or physicians nor a requirement to respond to the questionnaires for the patient (NICU infant) to participate in the study.\n\nEnrollment: 213 patients (NICU infants)", 'primaryPurpose': 'DIAGNOSTIC', 'maskingInfo': {'masking': 'SINGLE', 'maskingDescription': "Patients (NICU infants) and their parents, the patient's providers, and the enrollment staff will be blinded to the randomization arm they receive.", 'whoMasked': ['PARTICIPANT']}}, 'enrollmentInfo': {'count': 213, 'type': 'ACTUAL'}}

2024-03-01