STudying Acute exaceRbations and Response: The COPD STARR 2 study

STARR 2 Team Research Nurses – Helen Jeffers & Joanne Davies Contact interested patients (once initial contact has been made by GP surgery) Consent & randomise participants Conduct trial visits Dispense prednisolone/placebo CRF completion/data entry CI – Dr Mona Bafadhel

Trial Summary Current treatment of corticosteroids and antibiotics during an exacerbation = “one size fits all”. Follow on from STARR study which identified eosinophils as a biomarker during exacerbations. STARR 2 is looking at whether an eosinophil- directed therapy to personalise treatment reduces inappropriate and excessive drug therapy. 10 GP surgeries in Thames Valley GPs will be PI for each site

PI Responsibilities The PI has overall responsibility for activity at a site and it is their role to ensure that site staff are suitably trained for responsibilities he/she has delegated at the start and throughout the trial. The safety of participants should be overseen by the responsible PI at site. Before a trial is opened at a site, the PI should complete this training to ensure they have understood the trial and their responsibility as PI for STARR 2. In the event that a PI is off on annual leave, the PI should delegate responsibility to another GP to cover their duties in the interim. Especially to ensure there is cover in the event of an SAE. If a PI leaves the surgery, the trial manager needs to be notified immediately as they will give guidance on how to proceed at site.

Inclusion Criteria Participant is willing and able to give informed consent for participation in the trial. Male or Female, aged 40 years or above. Diagnosed with COPD (FEV1/FVC ratio <0.7). A history of at least 1 exacerbation in the previous 12 months, requiring systematic corticosteroids and/or antibiotics. Current or ex-smoker with at least 10 pack year smoking history. In the opinion of the research staff, is able and willing to comply with all trial requirements.

Exclusion Criteria History of atopic childhood asthma. Current history of primary lung malignancy or active pulmonary TB. Clinically relevant disease or disorder (past or present) Any clinically relevant lung disease, other than COPD considered by the investigator to be the primary diagnosis. An alternative cause for the increase in symptoms of COPD pneumonia pulmonary embolism pneumothorax primary ischaemic event – ST or Non ST elevation myocardial infarct and left ventricular failure

Exclusion Criteria (cont) A known allergy to the IMP (prednisolone), NIMP (doxycycline) or to any of the constituents of the placebo Patients on maintenance corticosteroids (prednisolone, hydrocortisone, fludrocortisone) Known adrenal insufficiency Currently enrolled in another CTIMP trial and receiving intervention as part of the trial. Pregnant and breast-feeding women.

Stable Visit This is a scheduled visit and occurs when the participant is 6 weeks free from an exacerbation. This visit can occur immediately following informed consent or following randomisation at a subsequent later date. All data obtained can be added directly to patient’s record. Spirometry; FeNO; MRC, HADS, VAS & CAT scores

Intervention Overview

Randomisation Procedure Randomisations for STARR 2 will be via RRAMP. This is a web based system that can be accessed from anywhere with an internet connection. The STARR 2 research nurses will perform the randomisations. The PIs at each site will receive notification emails through when a new participant has been randomised at their site. There is no emergency randomisation method.

Emergency Unblinding All emergency unblinding will be at the discretion of the local PI when clinically indicated for the safety of the patient. Emergency unblinding can be performed via RRAMP by the STARR 2 Research Nurses, the PI or the Trial Manager (if required). Non-emergency unblinding can be requested via the RRAMP system and will require approval by the CI.

Where Next? What the research is looking at and how this may influence future practice? Point of care testing Prescribing based on eosinophil count and CRP Personalised exacerbation treatment

Any questions? Contact Details: CI – Prof Mona Bafadhel: mona.bafadhel@ndm.ox.ac.uk Research Nurse – Helen Jeffers: helen.jeffers@ndm.ox.ac.uk Research Nurse – Joanne Davies: joanne.davies@ndm.ox.ac.uk Trial Manager – Hania Piotrowska: hania.piotrowska@ouh.nhs.uk – 01865 225552