Title: What is the clinical effectiveness and cost-effectiveness of nebulised saline in patients with chronic obstructive pulmonary disease (MucAct COPD Trial)?
Funder: Chief Scientist Office, Scotland

Abstract: Aim(s) of the research_x000D_ We want to study whether breathing in salty water through a nebuliser can help patients with Chronic Obstructive Pulmonary Disease (COPD) cough up phlegm, make them feel better and cut down the number of chest infections. We also would like to know whether this is better than taking tablets(carbocisteine), also thought to help patients clear phlegm from the airways._x000D_ A nebuliser is a machine that creates a mist, which can be inhaled through a mask or tube. The salty_x000D_ water can be inhaled through a nebuliser to help clear excess mucus from the airways and takes less_x000D_ than 10 minutes. In a small number of patients, treatment leads to increased wheeze and_x000D_ breathlessness, which can be helped by using an agent through the nebuliser to open the airways. If_x000D_ this does not help, the salty water treatment will be stopped. _x000D_ There is poor evidence of what treatments help clear mucus from the airways. Usually carbocisteine_x000D_ tablets are used (to help clear mucus from the airways). The study investigators believe inhaling salty_x000D_ water is better at clearing mucus from the airways and has additional beneficial effects combating_x000D_ bacteria and viral infection._x000D_ Background_x000D_ Some patients with COPD find it hard to clear sputum (phlegm) from the airways. Unfortunately,_x000D_ there’s no good evidence that shows the best treatment for patients._x000D_ How we will do the study_x000D_ We will select 860 patients with COPD throughout the UK._x000D_ Half of the group, at random, will inhale salty water through a nebuliser twice a day for 1 year. The_x000D_ other half will get carbocisteine tablets daily for 1 year. It is not possible for it to be a blind trial_x000D_ because the participants and clinician will obviously know the treatment given. Both groups will be_x000D_ taught chest clearance using a video of breathing and coughing techniques that they can use twice a_x000D_ day to help clear phlegm from the chest._x000D_ The main goal of the study is to see whether inhaled saline is better and is more cost effective than_x000D_ oral carbocisteine which is the traditional medication used. Theoretically, inhaled saline is better than_x000D_ carbocisteine at clearing phlegm in the airways. _x000D_ Ethics and data protection_x000D_ The study will only begin following approvals of the multi-centre research ethics committee, approval_x000D_ by the Medicines and Healthcare products Regulatory Agency (MHRA) and management approval._x000D_ Data protection will comply with General Data Protection Regulation (GDPR)._x000D_ Involving patients and the public_x000D_ Our grant proposal has been reviewed by the British Lung Foundation (BLF), University of Edinburgh_x000D_ Patient & Public Involvement (PPI) group based in the Usher Institute and the patient group_x000D_ “Breathtakers, Action for Bronchiectasis”. We amended our plans for the study after getting their_x000D_ feedback. The PPI group also helped with writing this lay summary. A member of the PPI group has_x000D_ now joined as a co-applicant and two separate members to join the steering committee for the trial_x000D_ who will link to the BLF patient advisory group._x000D_ Who will hear about the results_x000D_ We will present our findings at local, national and international meetings. The University of Edinburgh_x000D_ PPI group and BLF have also offered to help spread the word. This study won’t just help the NHS but_x000D_ could also be applied internationally - so we aim to publish the paper in an influential and widely read_x000D_ medical journal.

Lay abstract: 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? _x000D_ 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._x000D_ 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). _x000D_ Methods: This is an open pragmatic multi-centre parallel group randomised controlled trial (RCT) with process evaluation and health economic analysis. _x000D_ 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. _x000D_ 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. _x000D_ 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)._x000D_ 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._x000D_ Timelines for delivery_x000D_ Months 0-6: Study set up (including training and approvals); _x000D_ Months 7-14: Pilot study _x000D_ Months 15-35: Open remaining sites, complete recruitment _x000D_ Months 36-47: Complete follow up _x000D_ Months 48-53: Analysis and reporting _x000D_ 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._x000D_ 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.

Research activity codes: 5.1 PHARMACEUTICALS
Health categories: RESPIRATORY