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BronchiectasisPhase 3CLEARNCT04140214

Randomised Open Label Trial of Hypertonic Saline and Carbocisteine in Bronchiectasis (CLEAR)

A Phase 3 study testing Hypertonic saline and Carbocysteine 750 MG in people with Bronchiectasis, run by Belfast Health and Social Care Trust at 20 sites in United Kingdom.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

Patients with bronchiectasis (BE) suffer from a persistent cough, daily sputum expectoration, recurrent chest infections, and a poor health-related quality of life. Current guidelines for the management of BE highlight the lack of evidence to recommend mucoactive agents, such as hypertonic saline (HTS) and… Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Bronchiectasis
What is being tested?
Hypertonic saline and Carbocysteine 750 MG
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
288 participants
Where
20 sitesUnited Kingdom
Study dates
27 Jun 2018to 18 Dec 2024
Phase
Phase 3
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Diagnosis of BE on high resolution computed tomography(HRCT)/computed tomography (CT) scans
  • BE must be the primary respiratory diagnosis
  • One or more pulmonary exacerbations in the last year requiring antibiotics*
  • Production of daily sputum
  • Stable for 14 or more days before the first study visit with no changes to treatment
  • Willing to continue any other existing chronic medication throughout the study
  • Female subjects must be either surgically sterile, postmenopausal or agree to use effective contraception during the treatment period of the trial *This can include patient reported exacerbations

Who cannot join

  • Age <18 years old
  • Patients with cystic fibrosis (CF)
  • Patients with COPD as a primary respiratory diagnosis
  • Current smokers, female ex-smokers with greater than 20 pack years and male ex-smokers with greater than 25 pack years.
  • Forced expiratory volume in one second (FEV1) <30%
  • If being treated with long term macrolides, on treatment for less than one month before joining study
Show all 15Show fewer
  • Patients on regular isotonic saline
  • Treatment with HTS, carbocisteine or any mucolytics within the past 30 days
  • Known contraindication or intolerance to hypertonic saline or carbocisteine
  • Hypersensitivity to any of the active ingredients or the excipients of carbocisteine
  • Active peptic ulceration
  • Any heredity galactose intolerance, the Lapp-Lactase deficiency or glucose-galactose malabsorption
  • Patients unable to swallow oral capsules
  • Women who are pregnant or lactating
  • Participation in other trials of investigational products within 30 days

Trial locations and contacts

20 sites in 1 country.

20 sites in 1 country

United Kingdom20 sites

  • Stoke Mandeville Hospital

    Aylesbury, HP21 8AL

  • Belfast City Hospital, Belfast Health and Social Care Trust

    Belfast

  • Queen Elizabeth Hospital, University Hospital Birmingham NHS Foundation Trust

    Birmingham

  • Blackpool Teaching Hospitals NHS Foundation Trust

    Blackpool, FY3 8NR

  • Bradford Teaching Hospitals

    Bradford, BD9 6RJ

  • Royal Brompton Hospital, Royal Brompton and Harefield NHS Foundation Trust

    Brompton

  • Ninewells Hospital and Medical School, NHS Tayside

    Dundee

  • Royal Infirmary Edinburgh, NHS Lothian

    Edinburgh

  • Royal Free Hospital, Royal Free London NHS Foundation Trust

    Hamstead

  • Princess Alexandra Hospital, The Princess Alexandra Hospital NHS Trust

    Harlow

  • Royal Lancaster Infirmary, University Hospitals of Morecambe Bay NHS Foundation Trust

    Lancaster

  • Cardiff & Vale University Heath Board

    Llandough, CF64 2XX

  • Altnagelvin Area Hospital, Western Health and Social Care Trust

    Londonderry

  • Milton Keynes University Hospital

    Milton Keynes, MK6 5LD

  • Freeman Hospital, The Newcastle Upon Tyne Hospitals NHS Foundation Trust

    Newcastle

  • Northumbria NHS Foundation Trust

    North Shields, NE29 8NH

  • Churchill Hospital, Oxford University Hospitals NHS Foundation Trust

    Oxford

  • Southampton General Hospital, University Hospital Southampton NHS Foundation Trust

    Southampton

  • Royal Gwent Hospital, Aneurin Bevan University Health Board

    Wales

  • Sandwell & West Birmingham

    West Bromwich, B71 4HJ

Other trials in United Kingdom

About this study

Official title: A 2x2 Factorial Randomized Open Label Trial to Determine the Clinical and Cost-effectiveness of Hypertonic Saline (HTS) 6% and Carbocisteine for Airway Clearance Versus Usual Care Over 52 Weeks in Bronchiectasis

Patients with bronchiectasis (BE) suffer from a persistent cough, daily sputum expectoration, recurrent chest infections, and a poor health-related quality of life. Current guidelines for the management of BE highlight the lack of evidence to recommend mucoactive agents, such as hypertonic saline (HTS) and carbocisteine, to aid sputum-removal as part of standard care. The investigators hypothesise that mucoactive agents (HTS or cabocisteine, or a combination of both) are effective in reducing exacerbations over a 52-week period, compared to usual care.

Read the detailed description

Mucus hypersecretion is a clinical feature of BE. This mucus-retention aids bacterial infection that can lead to pulmonary exacerbations, which further develops the "viscous cycle" of mucus-retention, infection, inflammation and tissue damage. Mucoactive drugs target this cycle by potentially increasing the ability to expectorate sputum and/or decrease mucus hypersecretion.

The current guidelines indicate that mucoactives in combination with airway clearance may be considered to enhance sputum expectoration in BE, but the evidence to support their use is limited. Furthermore, evidence for the effectiveness of hypertonic saline (HTS) and carbocisteine is insufficient to recommend them within the management of BE. However, EMBARC/BRONCH-UK data show that BE centres do prescribe mucoactives. This is important because adherence to therapies in BE in general is low, decreases as the number of prescribed medications increases, and is also related to poorer patient outcomes, including the number of pulmonary exacerbations and quality of life. Therefore, it is essential that only those drugs that are effective should be prescribed for patients with BE. There are cost considerations associated with mucoactives, and there is a risk of polypharmacy side effects.

Unlike BE, relatively strong evidence exists to favour the use of both HTS and carbocisteine within other respiratory conditions. Therefore, this trial will answer important clinical questions about whether similar benefits can be demonstrated in BE by using a pragmatic design to explore the specific effects of mucoactive agents, and directly support, or refute, more targeted use of these drugs.

Patients will be randomised to one of four treatment groups: (i) standard care and twice daily nebulised HTS (6%), (ii) standard care and carbocisteine, (iii) standard care and combination of twice-daily nebulised HTS and carbocisteine, or (iv) standard care alone.

Conditions
Bronchiectasis
Being tested
Hypertonic saline, Carbocysteine 750 MG
Keywords
Respiratory, Mucoactive, Exacerbation, Hypertonic Saline, Carbocisteine, Airway Clearance
Medical subject headings
Bronchiectasis

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Hypertonic salineDrug

    Also called MucoClear 6%, HTS

    Nebulized hypertonic saline solution (6%)

  • Carbocysteine 750 MGDrug

    Also called Mucodyne

    Carbocisteine tablet

Study groups in NCT04140214
Study groupRoleWhat they receive
Standard Care and HTSExperimentalStandard care and twice-daily nebulised HTS (MucoClear 6%, PARI Pharma). Participants will be instructed to administer a 1 x 4 mL ampoule twice daily for 52 weeks using the eFlow rapid nebuliser and eTrack controller (PARI Pharma).
Receives: Drug: Hypertonic saline
Standard Care and CarbocisteineExperimentalStandard care and carbocisteine (750 mg three-times-per-day until visit 3, reducing to 750 mg two times per day) over 52 weeks.
Receives: Drug: Carbocysteine 750 MG
Standard Care and Combination of HTS and CarbocisteineExperimentalStandard care and combination of twice-daily nebulised HTS (MucoClear 6%, PARI Pharma) and carbocisteine. Participants will be instructed to administer a 1 x 4 mL ampoule twice daily for 52 weeks using the eFlow rapid nebuliser eFlow rapid nebuliser and eTrack controller (PARI Pharma). They will also be given carbocisteine (750 mg of three times per day until visit 3, reducing to 750 mg twice per day) over 52 weeks.
Receives: Drug: Hypertonic saline; Drug: Carbocysteine 750 MG
Standard Care OnlyNo interventionStandard care over 52 weeks. Patients in the standard care group will use airway clearance techniques in the management of their BE.

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Mean Number of Exacerbations

    Patient-reported exacerbations assessed using pre-defined criteria, including intensity and duration of symptoms, via modified Respiratory and Systemic Symptoms questionnaire.

    Measured: 52 weeks post-randomization

Secondary outcomes (12)

  1. Disease-Specific Health-Related Quality of Life

    Respiratory symptoms domain of quality of life with BE (QoL B) questionnaire.

    Measured: 52 weeks post-randomization

  2. Time to Next Exacerbation

    Exacerbations assessed using pre-defined criteria, including intensity and duration of symptoms, via modified Respiratory and Systemic Symptoms questionnaire.

    Measured: Over 52 weeks post-randomization

  3. Number of Days of Antibiotics for Exacerbations

    Days of antibiotic use directly related to pulmonary exacerbation; assessed using pre-defined criteria for exacerbations, including intensity and duration of symptoms via modified Respiratory and Systemic Symptoms questionnaire and through interview with participant.

    Measured: Over 52 weeks post-randomization

  4. Generic Health-Related Quality of Life (HRQoL)

    EQ-ED-5L questionnaire; a validated questionnaire that provides a simple descriptive profile and a single index value for health status.

    Measured: Assessed at baseline, and 2 weeks, 8 weeks, 26 weeks and 52 weeks post-randomization.

  5. Health Service Use

    Study-specific health-service use questionnaire to capture service use and details of prescribed medications (including antibiotics).

    Measured: 52 weeks post-randomization

  6. Quality Adjusted Life Years (QALY)

    Calculated by assessment of generic HRQoL measured using the EQ-5D-5L questionnaire. Responses will be converted to utility scores using the tariff recommended by NICE in their Guide to Technology Appraisal at the time of analysis. Currently this is the Crosswalk Value Set. The area under the curve method will be used to calculate Quality adjusted life years (QALYs).

    Measured: 52 weeks post-randomization

  7. Measurement of Health Impairment

    St. Georges Respiratory Questionnaire; designed to measure health impairment in those with COPD and asthma, and validated for use in the BE population.

    Part 1 : Symptoms component (frequency \& severity) with a 1, 3 or 12-month recall (best performance with 3- and 12-month recall); Part 2: Activities that cause or are limited by breathlessness; Impact components (social functioning, psychological disturbances resulting from airways disease) refer to current state as the recall.

    Scores range from 0 to 100, with higher scores indicating more limitations. Scaling of items Part I (Symptoms): several scales; Part II (Activity and Impacts): dichotomous (true/false) except last question (4-point Likert scale)

    Measured: Assessed at baseline, and 2 weeks, 8 weeks, 26 weeks and 52 weeks post-randomization.

  8. Patient Preferences for Treatment

    Measured via the TSQM version II questionnaire to assess four key dimensions of treatment satisfaction: effectiveness; side effects; convenience; and global satisfaction (score 0-100, higher scores indicate better satisfaction).

    Measured: Assessed at 2, 8, 26, and 52 weeks post-randomization.

  9. Number of Adverse Events

    Reported by the PI or designee via interview with patients.

    Measured: Over 52 weeks post-randomization

  10. Changes in Lung Function

    Spirometry testing to measure lung function parameters, to include FEV1, FVC, FEF25-75 and FEV1% predicted.

    Measured: 52 weeks post-randomization

  11. IMP Adherence

    Assessed using IMP Accountability Logs

    Measured: 52 weeks post-randomization

  12. HTS Adherence

    Assessed electronically via tracking of nebulizer use.

    Measured: 52 weeks post-randomization

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted25 Oct 2019
  2. Study start27 Jun 2018
  3. Primary completion30 Sep 2024
  4. Study completion18 Dec 2024

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Factorial
Model description
A superiority, 2x2 factorial randomised open label trial with a 52-week follow-up period.
Masking
None (open label)
Enrolment
288 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04140214
Sponsor's protocol ID
16178SE-AS
Acronym
CLEAR
Status last verified
Jan 2025
First submitted
17 May 2019
Last updated
2 May 2025
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No: Requests for data sharing will be reviewed on an individual basis by the Chief Investigator (CI) and the Trial Management Group (TMG).

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Hypertonic saline and Carbocysteine 750 MG in people with Bronchiectasis, run by Belfast Health and Social Care Trust at 20 sites in United Kingdom.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 7 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 2 May 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 20 sites in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Mean Number of Exacerbations (time frame: 52 weeks post-randomization). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04140214.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 May 2025.

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