Chronic airway disease (Asthma or COPD) Respiratory
Conditions
Interventions
Trial participants will enter the study on their established ICS/LABA ± LAMA therapy prior to trial entry (routine inhaled therapy)
Routine inhaled therapy will be replaced with study treatments, Rel
Sponsors
University of Leicester
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Clinically diagnosed airway disease (asthma or COPD) 2. Blood eosinophil count of = 0.2 x 109/L either at the clinic visit or any one time in the preceding 24 months 3. History of “Exacerbation prone airway disease” (defined as 2 or more exacerbations requiring oral corticosteroids and or antibiotics within 12 months of initial pre-screening review) 4. Male and female patients aged 18 years and over 5. Willing and able to consent to participate in trial 6. Able to use a smartphone device and comply with biomarker guided protocol
Exclusion criteria
Exclusion criteria: 1. Unable to give informed consent 2. Unable to use a smartphone device and or comply with biomarker guided protocol 3. Absence of eosinophilia (defined as persistently 450 msec at screening or baseline 7. History of previous hospital admission as pneumoniaa (with radiological lung changes) prior to 12 months of study screening 8. History of human immunodeficiency virus (HIV) or hepatitis B or C 9. History of active Malignancy in any organ system (diagnosis within last 12 months or ongoing active cancer treatment such as chemotherapy, radiotherapy, or immunotherapy 10. Patients whose treatment is considered palliative (life expectancy 2.0x upper limit of normal (ULN) 13.2. Total bilirubin >1.3 X ULN at screening (except for patients with Gilberts syndrome where suitability for inclusion will be left to the discretion of the local investigator)
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 1. Annualised rate of airway disease exacerbations from baseline to 24 weeks, with exacerbations defined as: 1.1. Mild exacerbations (any one of): 1.1.1. Nocturnal awakening(s) on at least 2 nights 1.1.2. Increase in short-acting beta agonist (SABA) use for at least 2 nights 1.1.3. =20% decrease in peak expiratory flow on at least 2 nights compared to the optimal run-in peak flow reading 1.1.4. =20% decrease in FEV1 compared to optimal run-in FEV1 reading 1.1.5. A visit to the emergency department (ED)/trial team for increased symptoms but not requiring additional systemic corticosteroids. 1.2. Moderate-to-severe exacerbation (any one of): 1.2.1. Use of systemic corticosteroids ±antibiotics, or an increase from a stable maintenance dose, for at least 3 days. A period of 7 days or more between additional corticosteroids will be defined as a separate event 1.2.3. An episode of hospitalization or ED (emergency department) visit because of increased airways disease symptoms, requiring systemic corticosteroids ± antibiotics Exacerbations will be captured via the electronic symptom diary supported by digital platform Atom5 and Nuvoair, with data collected three times per week to allow monitoring mild exacerbation events. 2. Annualised rate of all airway disease exacerbations from baseline visit to the study endpoint (24 weeks) | — |
Secondary
| Measure | Time frame |
|---|---|
| 1. Secondary outcome measures from baseline (week 0) to week 24: 1.1. Pre-bronchodilator Forced Expiratory Volume in 1 second (FEV1) and FEV1/FVC measured at study visits (weeks 0,12 & 24) 1.2. Compliance with biomarker algorithm-based treatment advisories during the trial (proportion of days in the month that participants adhere to algorithm-based treatment advisories over 24 weeks). Electronically monitored adherence profile (weeks 0, 4, 8,12 & 24) 1.3. St George’s Respiratory Questionnaire score (SGRQ) (weeks 0, 12 & 24) 1.4. Annualised rate of moderate to severe exacerbation events requiring oral corticosteroids or antibiotics 2. Exploratory (Clinical biomarkers): To compare the following outcome measures between the biomarker intervention arm and the standard of care arm: 2.1. Additional exacerbation outcomes: 2.1.1. Time to first moderate-severe exacerbation 2.1.2. Hospital or Emergency Department (ED) admissions due to exacerbations of airway disease 2.2. Biomarkers: 2.2.1. Change in blood eosinophil counts (weeks 0, 12 & 24) 2.3. Symptom questionnaires (Comparison of change over 24 weeks and responder analysis) 2.3.1. COPD Assessment Tool (CAT) for COPD participants 2.3.2. Asthma Control Test Score (ACT) for Asthma patients 2.3.3. Extended MRC dyspnoea score (eMRC) for participants with both asthma and COPD 3. Exploratory (Digital biomarkers): The following digital biomarkers will be collected and assessed as exploratory analyses at Imperial College, London 3.1. Composite Exacerbation Endpoints: Analysis of thrice weekly study acquired PEFR/FEV1, Reliever use and symptom scores with a view to deriving composite exacerbation endpoint measurements using threshold and slope-based indices. (weeks 0-12, 13-24 & 0-24) 3.2. Cough biomarker analysis (Nuvoair data): 3.2.1. Cough counts (weeks 0-12, 13-24 & 0-24) 3.2.2. Cough sound biomarkers (including frequency - median (range) and amplitude) (weeks 0-12, 13-24 & 0-24) 3.3. Physical activity monitor | — |
Countries
United Kingdom
Outcome results
None listed