PrecISE: Un ensayo adaptativo estratificado por biomarcadores de 5 intervenciones en asma grave: protocolo final y...

The National Institutes of Health initiated the Precision Medicine in Severe and/or Exacerbation Prone Asthma (PrecISE) program with the objective of implementing adaptive design strategies to test multiple new treatments in biomarker-identified patient subsets.

The PrecISE study sought to recruit a cohort of patients with severe asthma for a biomarker stratified adaptive trial of 5 different interventions.

Patients 12 years and older with a clinical diagnosis of asthma on a stable medical regimen consisting of at least medium dose inhaled corticosteroids (ICS) and a second controller were enrolled if their diagnosis could be confirmed by bronchodilator responsiveness on spirometry or airway hyperreactivity to methacholine. Protocol adaptations over the course of the study to biomarker sampling and enrichment, interventions studied, the statistical analysis plan, and sample size are described. Baseline characteristics of the cohort were analyzed.

358 participants were randomized. The four predictive biomarkers used for intervention randomization assignments were blood eosinophil counts (median 180, IQR 100-290 cells/μL), FeNO measurements (median 18, IQR 11-27 ppb), plasma IL-6 levels (median 2.5, IQR 1.6-3.6 pg/mL) and ADH5 risk genotypes (present in 253 (71%) participants). Blood eosinophils weakly correlated with FeNO measures (Rs=0.13, p=0.02) and IL-6 levels (Rs=0.17, p=0.002); otherwise, these biomarkers were independent from each other. Specific intervention results will be reported separately.

The PrecISE adaptive study design with multi-period crossovers is an efficient and novel way to study multiple interventions simultaneously in a heterogeneous disease such as asthma.