STABILISE: a multicentre, randomised, parallel group, superiority trial to investigate the use of BCG vaccine in altering immune response and exacerbation in chronic obstructive pulmonary disease (COPD)

Research question: Does BCG vaccination reduce exacerbations in patients with COPD? Background: Chronic obstructive pulmonary disease (COPD) is an airways diseases characterised by fixed airflow obstruction, alongside typical clinical history and radiology. It often overlaps with asthma or bronchiectasis. COPD affects almost 2m people in the UK. BCG vaccine has been used to prevent tuberculosis (TB) for over 70 years, however there is growing evidence that its protective effects may be broader via effects on trained immunity. Our hypothesis is that the vaccine will reduce infectious exacerbations of airways disease, and that there may be a greater effect for viral driven events. Aims and objectives 1. Determine whether BCG reduces rates of respiratory exacerbations at 12 months in patients who have a clinical diagnosis of COPD, and a history of 2 exacerbations in the preceding year 2. Compare the rate of hospitalisations for infective exacerbations, quality of life (QOL) and number of days of antibiotic and steroid therapy in the follow up period between intervention and placebo arms 3. Explore the immunological basis by which BCG may confer non-specific protection against infection 4. Determine acceptability of BCG vaccine for this purpose Methods: STABILISE is an individually randomised, multicentre, double blind, two arm, parallel group, clinical trial testing the efficacy of BCG vaccine to reduce moderate-severe exacerbations of COPD against placebo over 12 months. There is an internal pilot phase and a process evaluation. It will recruit 804 patients with COPD from secondary and primary care. Exploratory work to determine the mechanism by which BCG has its effects will be conducted through 3 tiers of testing; tier 1 is in all patients and assesses humoral immunity via dried blood spots (DBS). Tier 2 involves more detailed assessment of such using venepuncture. Tier 3 captures microbiological and immunological information at the start of exacerbations via patient submitted sputum, viral swab and DBS samples sent to the central lab by post. Follow up occurs at 12 months in person for all tiers, with 1 and 3 month visits for tier 2 only. All other data is collected remotely or submitted directly by patients. An embedded qualitative study will determine acceptability and suggest means of enhancing vaccine uptake, if effective. Timelines: STABILISE patients are being recruited over 2 years and followed up for 1 year, such that the overall study takes 4 years, accounting for set up times and analysis Anticipated impact and dissemination: Dissemination will occur through conferences and publications, as well as through the trial PPI group and a regular newsletter. Impact is anticipated through changes in guidance on vaccination schedule for airways disease patients