NHLBI TOPMed: TReating Children to Prevent EXacerbations of Asthma (TREXA)

This study is part of the NHLBI Trans-Omics for Precision Medicine (TOPMed) Whole Genome Sequencing Program. TOPMed is part of a broader Precision Medicine Initiative, which aims to provide disease treatments that are tailored to an individual's unique genes and environment. TOPMed will contribute to this initiative through the integration of whole-genome sequencing (WGS) and other -omics (e.g., metabolic profiles, protein and RNA expression patterns) data with molecular, behavioral, imaging, environmental, and clinical data. In doing so, this program aims to uncover factors that increase or decrease the risk of disease, to identify subtypes of disease, and to develop more targeted and personalized treatments. Two genotype call sets derived from WGS are now available, Freeze 9b (GRCh38) and Freeze 10b (GRCh38), with largely overlapping sample sets. Information about how to identify other TOPMed WGS accessions for cross-study analysis, as well as descriptions of TOPMed methods of data acquisition, data processing and quality control, are provided in the accompanying documents, "TOPMed Whole Genome Sequencing Project - Freeze 9b, Phases 1-4" and "TOPMed Whole Genome Sequencing Project - Freeze 10b, Phases 1-8". Please check the study list at the top of each of these methods documents to determine whether it applies to this study accession.

TREXA is a 44-week randomized, double-blind, double-masked, four-treatment, parallel trial that will evaluate the weaning strategy that provides the best protection against the development of exacerbations in children whose asthma is acceptably controlled on a low dose of ICS (per NAEPP guidelines). Following the 4 weeks of the run-in period on a 1x dose of ICS (100 µg fluticasone b.i.d. or its equivalent), children who do not meet the definition of acceptable asthma control will be randomized to the parallel BADGER protocol; those who meet the definition of acceptable asthma control will be enrolled into the 44-week treatment phase of the study. The primary outcome measure will be time to first exacerbation requiring a prednisone course.

• Study Weblinks:
  • TREXA
• Study Design:
  • Prospective Longitudinal Cohort
• Study Type:
  • Cohort
• dbGaP estimated ancestry using GRAF-pop
• Total number of consented subjects: 89
• Subject Sample Telemetry Report (SSTR)

Children with mild persistent asthma who are under good control with low dose inhaled corticosteroid (ICS) (100 µg fluticasone b.i.d. or its equivalent) for at least 8 weeks. Participants were eligible for inclusion if they were naive to controller treatment and had a history of one to two exacerbations in the previous year, if they were treated for the previous 8 weeks with a monotherapy other than inhaled corticosteroids, or if their illness was controlled for the previous 8 weeks on low-dose corticosteroids as monotherapy (≤160 µg daily with a beclomethasone equivalent). Participants were excluded from the study if they had a prebronchodilator forced expiratory volume in 1 s (FEV₁) of less than 60% predicted at the first visit; were admitted to hospital for asthma in the previous year; had any asthma exacerbation in the previous 3 months or more than two in the previous year; had a history of life-threatening asthma exacerbations that required intubation or mechanical ventilation, or that resulted in a hypoxic seizure.

• Primary Phenotype: Asthma

• Principal Investigator
  • Fernando Martinez, MD. University of Arizona, Tucson, AZ, USA.
• Funding Source
  • HL064307. National Institutes of Health, Bethesda, MD, USA.