TABLE 1

STIFLE study objectives and endpoints

ObjectivesEndpoints
  • Primary

  •  To characterise descriptively# the relationship between airway inflammation, asthma symptoms, lung function and reliever use, in the two treatment arms measured daily over 24 weeks of treatment

  • Individual patient profiles of daily variations over time in FENO (morning), asthma symptom scores (morning and evening), PEF and FEV1 (morning and evening), and reliever use

  • Secondary

  •  To characterise descriptively# airway inflammation, asthma symptoms, lung function and reliever use profiles surrounding an event in the two treatment arms

  • Individual patient profiles of daily variations over time in FENO (morning), asthma symptom scores (morning and evening), PEF and FEV1 (morning and evening), and reliever use between 14 days prior and 28 days after an event. Events include severe exacerbation, CompEx (full criteria) [26], single day (in 24 h) with six or more occasions of reliever medication use and FENO >50 ppb

  • Exploratory

  •  To describe patterns of inflammatory biomarkers in the two treatment arms at the start of an event+ (and every 4 days up to 12 days)

  • Individual patient profiles of inflammation biomarkers (blood biomarkers including eosinophils, EDN and CRP; sputum and nasal biomarkers) at the start of an event (and every 4 days up to 12 days)

  •  To characterise descriptively the daily variations in nasal biomarker measures during the first 30 days of treatment in the two treatment arms

  • Individual patient profiles of daily variations over time in nasal biomarkers during the first 30 days of treatment (subset of 30 patients)

Severe exacerbation events will be recorded, as they occur, on a case report form. Other events will be retrospectively defined and analysed based on the data collected during the study. FENO: exhaled nitric oxide fraction; PEF: peak expiratory flow; FEV1: forced expiratory volume in 1 s; CompEx: Composite Endpoint for Exacerbations; EDN: eosinophil-derived neurotoxin; CRP: C-reactive protein. #: this study has not been designed or powered to test any statistical hypothesis relating to a difference between the treatment arms; instead, airway inflammation, symptoms, lung function and reliever use profiles will be assessed descriptively and visually and will be modelled for each patient individually and by treatment, both over the 24-week period and during the time surrounding the various events. : use of systemic corticosteroids for ≥3 days, an emergency department visit due to asthma that requires systemic corticosteroids or inpatient hospitalisation due to asthma. +: events of interest include the first occurrence of either a severe exacerbation, symptom worsening (deterioration in two or more variables for two or more consecutive days: ≥15% decrease in PEF, ≥1.5 times increase in inhalations of reliever medication or ≥1 increase in asthma symptom score (or the absolute maximum score of 3), in the morning or evening, as compared with baseline), or a single day (in 24 h) with six or more occasions of reliever use.