Studying acute exacerbations and response: the COPD STARR 2 study

INTERVENTION: STARR 2 will be recruiting 228 participants with COPD from GP surgeries within the Thames Valley and South Midlands. A participant's involvement will last up until 12 months and will involve up to 5 visits. These visits will consist of CRF completion, questionnaires, breathing tests, urine testing, blood samples and spirometry. Participants will only be taking the trial drugs for 14 days during an exacerbation. Consented participants will be randomised (1:1) to standard or directed therapy using the centralised computer randomisation service RRAMP (https://rramp.octru.ox.ac.uk) provided by the Oxford Clinical Trials Research Unit (OCTRU). Randomisation will be undertaken using stratification to ensure a balanced allocation across treatment groups, stratified by eosinophil count, disease severity as measured by FEV at baseline and prior exacerbation history. All participants will be blinded to prednisolone therapy and receive open‐labelled antibiotics (doxycycline 100mg once per day for 7 days). Participants in the ‘blood eosinophil directed’ study arm will receive antibiotic (doxycycline, open labelled) and IMP (prednisolone or placebo) dependent on the blood eosinophil count at the randomisation (exacerbation visit). Participants in the ‘standard therapy’ study arm will receive IMP (prednisolone) and antibiotic (doxycycline, open labelled) irrespective of the blood eosinophil count at randomisation. Prednisolone therapy consists of prednisolone 30mg tablet taken orally per day for 14 days. Participants are followed up at days 14, 30, 90 with a medical review of notes at 12 months. CONDITION: Specialty: Respiratory disorders, Primary sub‐specialty: Respiratory disorders; UKCRC code/ Disease: Respiratory/ Chronic lower respiratory diseases ; Respiratory PRIMARY OUTCOME: Efficacy of blood‐eosinophil directed corticosteroid therapy compared to standard care measured by looking at the frequency of participants needing re‐treatment, hospitalisation, death at 30 and 90 days SECONDARY OUTCOME: Measured at baseline, day 14, 30 and 90:; 1. Quality of life, measured using CAT and EQ‐5D; 2. Symptoms, measured using VAS; 3. Lung function, measured using FEV1; 3. Healthcare utilisation, measured using exacerbation frequency in 12 months ; ; Exploratory outcome measures: ; 1. Stability of blood eosinophils, measured by the change in blood eosinophil counts at all visits (except 12 months); 2. Stability of mediatory levels in the blood, measured by looking at the change in inflammatory mediators during a stable state and at exacerbation INCLUSION CRITERIA: 1. Participant is willing and able to give informed consent for participation in the trial 2. Male or female, aged 40 years or above 3. Diagnosed with COPD (primary or secondary care diagnosis) with spirometric confirmation of airflow obstruction (FEV1/FVC ratio <0.7) 4. A history of at least 1 exacerbation in the previous 12 months, requiring systemic corticosteroids and/or antibiotics 5. Current or ex‐smoker with at least a 10 pack year smoking history 6. In the opinion of the research staff, is able and willing to comply with all trial requirements