What is the clinical effectiveness and cost-effectiveness of nebulised saline in patients with chronic obstructive pulmonary disease (MucAct COPD Trial)?

Research question: Over a one year period, what is the clinical effectiveness and cost-effectiveness of nebulised 7% sodium chloride compared with oral carbocisteine in patients with COPD who have difficulty in expectorating sputum? Background: Some patients with COPD find it hard to expectorate sputum from the airways. Randomised controlled trials are needed now to improve the evidence base of both treatments and a head-to-head comparison between 7% sodium chloride and carbocisteine is required. Aims and objectives: The main aim of this trial is to assess whether nebulised 7% sodium chloride over one year with Active Cycle Breathing Technique (ACBT) airways clearance is superior compared with oral carbocisteine with ACBT over one year in leading to a 2 Unit or greater increase in the COPD Assessment Test (CAT). Methods: This is an open pragmatic multi-centre parallel group randomised controlled trial (RCT) with process evaluation and health economic analysis. It is a two-armed study. Treatment is for one year to even out known seasonal effects. 860 participants will be recruited from 10-20 primary care and secondary care out-patient clinics throughout the UK. We are aiming to recruit 2 patients per calendar month per site months 7-35. There is a built-in pilot study (months 7-14) and we will continue to the full stage if we have successfully: 1] obtained approvals and performed research nurse training; 2] opened at least 4 sites to recruitment; 3] randomised at least 50 trial participants. Randomisation will be done centrally by the Edinburgh Clinical Trials Unit, will ensure allocation concealment and will be stratified for current smoking status and COPD severity (GOLD class C+D). Participants in the active arm will receive twice daily nebulised 7% sodium chloride + self-administered ACBT chest clearance for 52 weeks. Participants randomised to the comparator arm will receive oral carbocisteine (750 mg of carbocisteine three times per day for 8 weeks, reducing to 750 mg twice per day over 44 weeks) + self-administered ACBT chest clearance. The doses of carbocisteine used are the recommended doses from the 2019 British National Formula. Timelines for delivery Months 0-6: Study set up (including training and approvals); Months 7-14: Pilot study Months 15-35: Open remaining sites, complete recruitment Months 36-47: Complete follow up Months 48-53: Analysis and reporting Anticipated impact and dissemination: This will be a major UK study and we expect to find definitive evidence in relation to whether nebulised 7% sodium chloride is clinically and cost-effective in patients with COPD that have difficulty in sputum expectoration. If so, this will offer an evidenced- based therapy that is natural and non-antibiotic based. By including a comprehensive process evaluation plan, we will be able to improve treatment adherence and promote the best ways to deliver the intervention sustainably in the NHS if effectiveness is demonstrated. We will present our findings at local, national and international meetings. The British Lung Foundation will help disseminate the results to professionals and affected members of the public and we aim to publish the paper in an influential and widely read medical journal with high impact factor.