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

NCT ID: NCT04140214

Last Updated: 2025-05-02

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

288 participants

Study Classification

INTERVENTIONAL

Study Start Date

2018-06-27

Study Completion Date

2024-12-18

Brief Summary

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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.

Detailed Description

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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

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Bronchiectasis

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

FACTORIAL

A superiority, 2x2 factorial randomised open label trial with a 52-week follow-up period.
Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Standard Care and HTS

Standard 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).

Group Type EXPERIMENTAL

Hypertonic saline

Intervention Type DRUG

Nebulized hypertonic saline solution (6%)

Standard Care and Carbocisteine

Standard care and carbocisteine (750 mg three-times-per-day until visit 3, reducing to 750 mg two times per day) over 52 weeks.

Group Type EXPERIMENTAL

Carbocysteine 750 MG

Intervention Type DRUG

Carbocisteine tablet

Standard Care and Combination of HTS and Carbocisteine

Standard 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.

Group Type EXPERIMENTAL

Hypertonic saline

Intervention Type DRUG

Nebulized hypertonic saline solution (6%)

Carbocysteine 750 MG

Intervention Type DRUG

Carbocisteine tablet

Standard Care Only

Standard care over 52 weeks. Patients in the standard care group will use airway clearance techniques in the management of their BE.

Group Type NO_INTERVENTION

No interventions assigned to this group

Interventions

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Hypertonic saline

Nebulized hypertonic saline solution (6%)

Intervention Type DRUG

Carbocysteine 750 MG

Carbocisteine tablet

Intervention Type DRUG

Other Intervention Names

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MucoClear 6% HTS Mucodyne

Eligibility Criteria

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Inclusion Criteria

* 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

Exclusion Criteria

* 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
* 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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Queen's University, Belfast

OTHER

Sponsor Role collaborator

Belfast Health and Social Care Trust

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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J. Stuart Elborn

Role: PRINCIPAL_INVESTIGATOR

Queen's University, Belfast

Locations

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Stoke Mandeville Hospital

Aylesbury, , United Kingdom

Site Status

Belfast City Hospital, Belfast Health and Social Care Trust

Belfast, , United Kingdom

Site Status

Queen Elizabeth Hospital, University Hospital Birmingham NHS Foundation Trust

Birmingham, , United Kingdom

Site Status

Blackpool Teaching Hospitals NHS Foundation Trust

Blackpool, , United Kingdom

Site Status

Bradford Teaching Hospitals

Bradford, , United Kingdom

Site Status

Royal Brompton Hospital, Royal Brompton and Harefield NHS Foundation Trust

Brompton, , United Kingdom

Site Status

Ninewells Hospital and Medical School, NHS Tayside

Dundee, , United Kingdom

Site Status

Royal Infirmary Edinburgh, NHS Lothian

Edinburgh, , United Kingdom

Site Status

Royal Free Hospital, Royal Free London NHS Foundation Trust

Hamstead, , United Kingdom

Site Status

Princess Alexandra Hospital, The Princess Alexandra Hospital NHS Trust

Harlow, , United Kingdom

Site Status

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

Lancaster, , United Kingdom

Site Status

Cardiff & Vale University Heath Board

Llandough, , United Kingdom

Site Status

Altnagelvin Area Hospital, Western Health and Social Care Trust

Londonderry, , United Kingdom

Site Status

Milton Keynes University Hospital

Milton Keynes, , United Kingdom

Site Status

Freeman Hospital, The Newcastle Upon Tyne Hospitals NHS Foundation Trust

Newcastle, , United Kingdom

Site Status

Northumbria NHS Foundation Trust

North Shields, , United Kingdom

Site Status

Churchill Hospital, Oxford University Hospitals NHS Foundation Trust

Oxford, , United Kingdom

Site Status

Southampton General Hospital, University Hospital Southampton NHS Foundation Trust

Southampton, , United Kingdom

Site Status

Royal Gwent Hospital, Aneurin Bevan University Health Board

Wales, , United Kingdom

Site Status

Sandwell & West Birmingham

West Bromwich, , United Kingdom

Site Status

Countries

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United Kingdom

Other Identifiers

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16178SE-AS

Identifier Type: -

Identifier Source: org_study_id

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