What is the clinical effectiveness and cost-effectiveness of nebulised 7% sodium chloride in patients with chronic obstructive pulmonary disease?
| ISRCTN | ISRCTN10249134 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN10249134 |
| EudraCT/CTIS number | 2020-001949-39 |
| IRAS number | 281629 |
| Secondary identifying numbers | AC20047, HTA - NIHR128443, IRAS 281629 |
- Submission date
- 03/03/2021
- Registration date
- 01/06/2021
- Last edited
- 13/08/2025
- Recruitment status
- No longer recruiting
- Overall study status
- Completed
- Condition category
- Respiratory
Plain English summary of protocol
Background and study aims
Chronic obstructive pulmonary disease (COPD) is a chronic inflammatory lung disease that causes obstructed airflow from the lungs. Symptoms include breathing difficulty, cough, mucus (sputum) production and wheezing.
We want to study whether breathing in salty water through a nebuliser can help patients with COPD cough up phlegm, make them feel better and cut down the number of chest infections they have. We also would like to know whether this is better than taking capsules (carbocisteine), also thought to help patients clear phlegm from the airways.
A nebuliser is a machine that creates a mist, which can be inhaled through a mask or tube. The salty water can be inhaled through a nebuliser to help clear excess mucus from the airways. There is poor evidence of what treatments help clear mucus from the airways. Usually carbocisteine tablets are used (to help clear mucus from the airways). The study investigators believe inhaling salty water is better at clearing mucus from the airways and has additional beneficial effects combating bacterial and viral infection.
Who can participate?
Participants aged 18 years or older with COPD that have either chronic bronchitis and/or associated bronchiectasis and have self-reported difficulty self-expectorating
What does the study involve?
We will recruit 860 patients with COPD throughout the UK.
Half of the group, at random, will inhale salty water through a nebuliser twice a day for 1 year. The other half will get carbocisteine capsules daily for 1 year. It is not possible for it to be a blind trial because the participants and clinician will obviously know the treatment given. Both groups will be taught chest clearance using a video of breathing and coughing techniques that they can use twice a day to help clear phlegm from the chest.
The main goal of the study is to see whether inhaled sodium chloride is better and is more cost-effective than oral carbocisteine which is the traditional medication used. Theoretically, inhaled sodium chloride is better than carbocisteine at clearing phlegm in the airways.
Participants will be asked to attend three appointments in total – one to join the study and again at 6 months and 1 year.
What are the possible benefits and risks of participating?
There are no direct benefits to taking part in this study, but the results from this study might help to improve the healthcare of patients in the future.
There are not thought to be many disadvantages to taking part in the study. It does involve taking time to attend three appointments and undergo tests, complete diaries each week for a year and complete three questionnaires which might not find convenient.
Some patients may experience side effects from taking the study medications. Like with any new medication there is a risk of allergic reaction.
Where is the study run from?
NHS Lothian (UK)
When is the study starting and how long is it expected to run for?
June 2020 to November 2024
Who is funding the study?
The NIHR Health Technology Assessment Programme (UK)
Who is the main contact?
1. Beatrice Selby, bselby@ed.ac.uk
2. Prof. Adam Hill, adam.hill@nhs.scot
Contact information
Public
Edinburgh Clinical Trials Unit
Usher Institute, University of Edinburgh
5-7 Little France Road
Edinburgh
EH16 4UX
United Kingdom
| Phone | +44 (0)131 651 9975 |
|---|---|
| bselby@ed.ac.uk |
Scientific
Department of Respiratory Medicine
Royal Infirmary of Edinburgh
51 Little France Crescent
Edinburgh
EH16 4SA
United Kingdom
 ORCID ID |
0000-0002-1789-9257 |
|---|---|
| Phone | +44 (0)131 242 1921 |
| adam.hill@nhs.scot |
Study information
| Study design | Open pragmatic UK multi-centre parallel randomized controlled trial with process evaluation and health economic analysis |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Randomised controlled trial |
| Study setting(s) | Hospital |
| Study type | Treatment |
| Participant information sheet | Not available in web format, please use contact details to request a participant information sheet. |
| Scientific title | An open pragmatic UK multi-centre parallel randomised controlled trial with process evaluation and health economic analysis in participants with COPD that have either chronic bronchitis and/ or associated bronchiectasis that have self-reported difficulty self-expectorating to assess whether nebulised 7% sodium chloride plus Active Cycle Breathing Technique (ACBT) is superior compared with carbocisteine plus ACBT when comparing the change in COPD Assessment Tests (CAT) over one year period. |
| Study acronym | MucAct COPD |
| Study objectives | This study will provide knowledge on whether hypertonic sodium chloride is superior to carbocisteine in aiding sputum expectoration. In addition to improving sputum clearance, it is expected that there will be a prolongation in time to first exacerbation and overall a reduced number of exacerbations over one year. |
| Ethics approval(s) | Approved 09/04/2021, East Midlands - Leicester South Research Ethics Committee (The Old Chapel, Royal Standard Place, Nottingham, NG1 6FS, UK; +44(0)207 1048310; leicestersouth.rec@hra.nhs.uk), ref: 21/EM/0074 |
| Health condition(s) or problem(s) studied | Participants with Chronic Obstructive Pulmonary Disease that have either chronic bronchitis and/or associated bronchiectasis that have self-reported difficulty self-expectorating |
| Intervention | Participants will be randomised on a 1:1 basis to nebulised 7% sodium chloride plus ACBT or 750mg carbocisteine plus ACBT. The randomisation system will include allocation concealment and stratification for current smoking status, COPD severity (GOLD class 1 and 2 versus 3 and 4). The active arm will receive twice daily nebulised 7% sodium chloride + self-administered ACBT chest clearance. The participants are self-administering nebulised 7% sodium chloride and will be allowed to increase the frequency of use up to a maximum of 6 times per day during respiratory tract infections (minimum four times daily where possible). Participants allocated to the nebulised 7% sodium chloride arm will be instructed to administer a 1 x 4 mL ampoule twice daily for 52 weeks using the nebuliser provided by their local study team. Nebulisation takes less than 10 minutes. Some patients have bronchospasm with nebulised 7% sodium chloride. If these symptoms develop, treatment with nebulised 2.5mg salbutamol is recommended prior to taking the nebulised 7% sodium chloride. Nebulised 2.5mg salbutamol can also be used post hypertonic sodium chloride if needed. The comparator arm with carbocisteine 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 dose of carbocisteine is in accordance with the British National Formula (BNF). |
| Intervention type | Drug |
| Pharmaceutical study type(s) | |
| Phase | Phase III |
| Drug / device / biological / vaccine name(s) | Nebulised sodium chloride, carbocisteine |
| Primary outcome measure | Impact of COPD measured using the COPD Assessment Test (CAT) at baseline and one year |
| Secondary outcome measures | 1. Health related quality of life: 1.1. CAT score at baseline and 6 months 1.2. Quality of life assessment using the Leicester Cough Questionnaire and St. George’s Respiratory Questionnaire at 6 months and 1 year 2. Exacerbations and time to first exacerbation: 2.1. Number of exacerbations over a one year period requiring antibiotic therapy and/or systemic steroid treatment measured using exacerbation diaries when exacerbation is reported by the patient 2.2. Time to first exacerbation requiring antibiotic therapy and/or systemic steroids over one year measured using exacerbation diaries when exacerbation is reported by the participant 2.3. Proportion of exacerbations needing antibiotic therapy over one year measured using exacerbation diaries when exacerbation is reported by the patient and concomitant medication recording 2.4. Number of upper respiratory tract infections (URTI) over a one year period) assessed using the Wisconsin Upper Respiratory Symptom Survey-24 (WURSS-24) 2.5. Overall and COPD related hospital attendances/admissions over one year measured using healthcare usage questionnaire at baseline, 6 months and 12 months 2.6. Use of nebulised 7% sodium chloride in exacerbations measured using participant reported daily diaries 3. Potential pathogen microorganisms and viruses from sputum samples and combined nose and throat swabs: 3.1. Proportion being infected with a potential pathogenic organism and viruses at 6 months and one year (from sputum samples and combined nose and throat swabs (if taken as part of standard care)) 4. Viral transmissibility (household contacts to participant and participant to household contacts) measured using participant reported daily diaries 5. Lung function: 5.1. Forced Expired Volume in 1 second (FEV1), forced vital capacity (FVC) and mid-expiratory flows at 6 months and one year 6. Health economic benefits: 6.1. Cost per Quality Adjusted Life Year (QALY) a) over one year and b) modelled over a lifetime horizon measured using healthcare usage questionnaire at baseline, 6 months and 12 months 7. Adverse effects over one year measured using participant reported daily diaries 8. Adherence with interventions assessed by weekly participant charts and enquired at study appointments over one year |
| Overall study start date | 01/06/2020 |
| Completion date | 14/11/2024 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Adult |
| Lower age limit | 18 Years |
| Sex | Both |
| Target number of participants | 860 |
| Total final enrolment | 206 |
| Key inclusion criteria | 1. Patients ≥18 years old 2. Have COPD as the predominant respiratory diagnosis 3. Meet Medical Research Council (MRC) definition of chronic bronchitis, defined epidemiologically as cough and sputum production for ≥3 months per year in at least 2 consecutive years and/or have associated bronchiectasis on computed tomography of the chest 4. Self-reported difficulty in expectoration (determined from the medical notes and/or participant). If from the participant, this will be documented in the medical notes |
| Key exclusion criteria | Current participant exclusion criteria as of 16/12/2022: 1. Patients that do not have the capacity to consent (determined by clinician or member of the research team) 2. Patients with active malignancy 3. Patients with a solid organ transplant 4. Patients with active tuberculosis 5. Patients who are in end-of-life care 6. Patients who have had treatment with nebulised hypertonic sodium chloride, carbocisteine or any muco-active treatments within the past 7 days* 7. Patients who are established on long-term antibiotic therapy for less than 3 months 8. Patients who have had an exacerbation within the past 14 days requiring treatment with antibiotics and/or steroids** 9. Known contraindication or intolerance to nebulised 7% sodium chloride or carbocisteine or any hypersensitivity to the active ingredients or the excipients of carbocisteine 10. Active peptic ulceration; any known hereditary galactose intolerance, Lapp-Lactase deficiency or glucose-galactose malabsorption 11. Women who are pregnant or currently breastfeeding 12. Women of childbearing potential*** not taking appropriate contraception****. Contraception must be continued for a minimum of 30 days after the end of the IMP dosing schedule. 13. Participation in another Clinical Trial of an Investigational Medicinal Product (CTIMP) within the last 30 days 14. Previous recruitment to the study 15. Participants indicating that they are unable to comply with the study protocol prior to randomisation including those unable to complete participant questionnaires *If participants have been on treatment with nebulised 7% sodium chloride, carbocisteine or any muco-active treatments within the past 7 days, they need to come off these treatments for 7 days and remain clinically stable in order to be eligible for the study **14 days from the start of the recent exacerbation *** A woman is considered of childbearing potential (WOCBP), i.e. fertile, following menarche and until becoming post-menopausal unless permanently sterile. Permanent sterilisation methods include hysterectomy, bilateral salpingectomy and bilateral oophorectomy. A postmenopausal state is defined as no menses for 12 months without an alternative medical cause. A high follicle-stimulating hormone (FSH) level in the postmenopausal range may be used to confirm a post-menopausal state in women not using hormonal contraception or hormone replacement therapy. However, in the absence of 12 months of amenorrhea, a single FSH measurement is insufficient. ****Acceptable contraception in women of childbearing age is a “highly effective” contraceptive measure as defined by the Clinical Trials Facilitation Group and includes combined (oestrogen and progesterone containing) or progesterone-only contraception associated with inhibition of ovulation, or intrauterine device or bilateral tubal occlusion (http://www.hma.eu/fileadmin/dateien/Human_Medicines/01-About_HMA/Working_Groups/CTFG/2014_09_HMA_CTFG_Contraception.pdf). Previous participant exclusion criteria: 1. Patients that do not have capacity to consent (determined by clinician or member of the research team) 2. Patients with an active malignancy 3. Patients with a solid organ transplant 4. Patients with active tuberculosis 5. Patients who are in end-of-life care 6. Patients who have had treatment with nebulised hypertonic sodium chloride, carbocisteine or any muco-active treatments within the past 30 days* 7. Patients established on long-term antibiotic therapy for less than 3 months 8. Patients who have had an exacerbation within the past 30 days requiring treatment with antibiotics and/or steroids 9. Known contraindication or intolerance to nebulised 7% sodium chloride or carbocisteine or any hypersensitivity to the active ingredients or the excipients of carbocisteine 10. Active peptic ulceration; any known hereditary galactose intolerance, Lapp-Lactase deficiency or glucose galactose malabsorption; patients unable to swallow oral capsules 11. Women who are pregnant or currently breastfeeding 12. Women of childbearing potential** not taking appropriate contraception***. Contraception must be continued for a minimum of 30 days after the end of the IMP dosing schedule 13. Participation in another Clinical Trial of an Investigational Medicinal Product (CTIMP) within the last 30 days 14. Previous recruitment to the study 15. Participants indicating that they are unable to comply with the study protocol prior to randomisation including those unable to complete participant questionnaires *If participants have been on treatment with nebulised 7% sodium chloride, carbocisteine or any muco-active treatments within the past 30 days, they need to come off these treatments for 30 days and remain clinically stable in order to be eligible for the study. ** A woman is considered of childbearing potential (WOCBP), i.e. fertile, following menarche and until becoming post-menopausal unless permanently sterile. Permanent sterilisation methods include hysterectomy, bilateral salpingectomy and bilateral oophorectomy. A postmenopausal state is defined as no menses for 12 months without an alternative medical cause. A high follicle stimulating hormone (FSH) level in the postmenopausal range may be used to confirm a post-menopausal state in women not using hormonal contraception or hormonal replacement therapy. However in the absence of 12 months of amenorrhea, a single FSH measurement is insufficient. ***Acceptable contraception in women of childbearing age is a “highly effective” contraceptive measure as defined by the Clinical Trials Facilitation Group and includes combined (oestrogen and progesterone containing) or progesterone-only contraception associated with inhibition of ovulation, or intrauterine device or bilateral tubal occlusion (http://www.hma.eu/fileadmin/dateien/Human_Medicines/01-About_HMA/Working_Groups/CTFG/2014_09_HMA_CTFG_Contraception.pdf). |
| Date of first enrolment | 01/05/2021 |
| Date of final enrolment | 01/12/2023 |
Locations
Countries of recruitment
- England
- Scotland
- United Kingdom
Study participating centres
51 Little France Crescent
Edinburgh
EH16 4SA
United Kingdom
Barrack Road
Exeter
EX2 5DW
United Kingdom
1055 Great Western Road
Glasgow
G4 0SF
United Kingdom
50 Netherton Street
Wishaw
ML2 0DP
United Kingdom
Freeman Road
Newcastle-upon-tyne
NE7 7DN
United Kingdom
Duckworth Lane
Bradford
BD9 6RJ
United Kingdom
Combe Park
Bath
BA1 3NG
United Kingdom
Great Western Road
Gloucester
GL1 3NN
United Kingdom
Inverness
IV2 3UJ
United Kingdom
Bordesley Green
Birmingham
B9 5SS
United Kingdom
Sutton Coldfield
B75 7RR
United Kingdom
Orpington
BR6 8ND
United Kingdom
East Kilbride
G75 8RG
United Kingdom
Middlesbrough
TS4 3BW
United Kingdom
Macclesfield
SK10 3BL
United Kingdom
Walsall
WS2 9PS
United Kingdom
Aberdeen
AB25 2ZN
United Kingdom
Mindelsohn Way
Edgbaston
Birmingham
B15 2GW
United Kingdom
Kirkcaldy
KY2 5AH
United Kingdom
Sponsor information
University/education
Academic and Clinical Central Office for Research and Development (ACCORD)
Research & Governance
University of Edinburgh
Queen’s Medical Research Institute
47 Little France Crescent
Edinburgh
EH16 4TJ
Scotland
United Kingdom
| Phone | +44 (0)131 242 9418 |
|---|---|
| enquiries@accord.scot | |
| Website | https://www.accord.scot/ |
"ROR" |
https://ror.org/01x6s1m65 |
Funders
Funder type
Government
Government organisation / National government
- Alternative name(s)
- NIHR Health Technology Assessment Programme, HTA
- Location
- United Kingdom
Results and Publications
| Intention to publish date | 30/06/2026 |
|---|---|
| Individual participant data (IPD) Intention to share | No |
| IPD sharing plan summary | Data sharing statement to be made available at a later date |
| Publication and dissemination plan | The Clinical Study Report (CSR) will be submitted to the Sponsor and REC within 1 year of the end of the study. Where acceptable, a published journal article may be submitted as the CSR. The Chief Investigator will provide the CSR to ACCORD, for review, prior to finalization. The clinical study report may be used for publication and presentation at scientific meetings. Investigators have the right to publish orally or in writing the results of the study. The results of the study, together with other mandated information, will be uploaded to the European clinical trials database within 1 year of the end of the study. The findings will be presented at local, national and international meetings. The PPI group and the British Lung Foundation will help disseminate the results to professionals and affected members of the public and the paper will be submitted for publication in an influential and widely read medical journal with high impact factor. |
| IPD sharing plan | The current data sharing plans for this study are unknown and will be available at a later date |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| HRA research summary | 28/06/2023 | No | No | ||
| Protocol file | version 4 | 09/08/2022 | 13/08/2025 | No | No |
Additional files
Editorial Notes
13/08/2025: The following changes were made to the trial record:
1. The completion date was changed from 30/06/2025 to 14/11/2024.
2. Uploaded protocol (not peer-reviewed) as an additional file.
19/12/2024: The following changes were made to the trial record:
1. The public contact was changed.
2. The study participating centres Queen Elizabeth University Hospital, Royal Free Hospital, University Hospital of North Tees, St Marys Hospital, St Georges Hospital were removed and University Hospitals Birmingham NHS Foundation Trust, Victoria Hospital were added.
18/12/2023: The following changes have been made:
1. The recruitment end date was changed from 01/08/2023 to 01/12/2023.
2. The overall study end date was changed from 31/08/2024 to 30/06/2025.
3. The intention to publish date was changed from 01/01/2026 to 30/06/2026.
4. Total final enrolment added.
5. Contact details updated.
16/12/2022: The following changes have been made:
1. The participant exclusion criteria have been changed.
2. The Royal Cornwall Hospital and Torbay Hospital were removed from the trial participating centres.
3. The Raigmore Hospital, Birmingham Heartlands Hospital, Birmingham Good Hope Hospital, Castle Hill Hospital, Princess Royal University Hospital, University Hospitals Hairmyres, Victoria Hospital, The James Cook University Hospital, University Hospital North Tees, St Marys Hospital, Macclesfield District General Hospital, Walsall Manor Hospital, Aberdeen Royal Infirmary and St George’s Hospital were added to the trial participating centres.
03/03/2021: Trial's existence confirmed by the National Institute for Health Research (NIHR) (UK).
