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

NCT04140214 | Completed Phase 3 DMC

• 1 other identifier: 16178SE-AS
• Study Type: interventional
• Target: 288
• Locations: 1 country
• Sites: 20

Brief 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 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.

Conditions

Bronchiectasis

Keywords

Respiratory; Mucoactive; Exacerbation; Hypertonic Saline; Carbocisteine; Airway Clearance

Outcome Measures

Primary Outcomes (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.

  52 weeks post-randomization

Secondary Outcomes (12)

• Disease-Specific Health-Related Quality of Life

  52 weeks post-randomization

• Time to Next Exacerbation

  Over 52 weeks post-randomization

• Number of Days of Antibiotics for Exacerbations

  Over 52 weeks post-randomization

• Generic Health-Related Quality of Life (HRQoL)

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

• Health Service Use

  52 weeks post-randomization

Study Arms (4)

Standard Care and HTS

EXPERIMENTAL

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).

Drug: Hypertonic saline

Standard Care and Carbocisteine

EXPERIMENTAL

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

Drug: Carbocysteine 750 MG

Standard Care and Combination of HTS and Carbocisteine

EXPERIMENTAL

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.

Drug: Hypertonic saline; Drug: Carbocysteine 750 MG

Standard Care Only

NO INTERVENTION

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

Interventions

Hypertonic saline DRUG

Nebulized hypertonic saline solution (6%)

Also known as: MucoClear 6%, HTS

Standard Care and Combination of HTS and Carbocisteine; Standard Care and HTS

Carbocysteine 750 MG DRUG

Carbocisteine tablet

Also known as: Mucodyne

Standard Care and Carbocisteine; Standard Care and Combination of HTS and Carbocisteine

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Belfast Health and Social Care Trust: lead
• Queen's University, Belfast: collaborator

Study Sites (20)

Stoke Mandeville Hospital

Aylesbury, HP21 8AL, United Kingdom

Location

Belfast City Hospital, Belfast Health and Social Care Trust

Belfast, United Kingdom

Location

Queen Elizabeth Hospital, University Hospital Birmingham NHS Foundation Trust

Birmingham, United Kingdom

Location

Blackpool Teaching Hospitals NHS Foundation Trust

Blackpool, FY3 8NR, United Kingdom

Location

Bradford Teaching Hospitals

Bradford, BD9 6RJ, United Kingdom

Location

Royal Brompton Hospital, Royal Brompton and Harefield NHS Foundation Trust

Brompton, United Kingdom

Location

Ninewells Hospital and Medical School, NHS Tayside

Dundee, United Kingdom

Location

Royal Infirmary Edinburgh, NHS Lothian

Edinburgh, United Kingdom

Location

Royal Free Hospital, Royal Free London NHS Foundation Trust

Hamstead, United Kingdom

Location

Princess Alexandra Hospital, The Princess Alexandra Hospital NHS Trust

Harlow, United Kingdom

Location

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

Lancaster, United Kingdom

Location

Cardiff & Vale University Heath Board

Llandough, CF64 2XX, United Kingdom

Location

Altnagelvin Area Hospital, Western Health and Social Care Trust

Londonderry, United Kingdom

Location

Milton Keynes University Hospital

Milton Keynes, MK6 5LD, United Kingdom

Location

Freeman Hospital, The Newcastle Upon Tyne Hospitals NHS Foundation Trust

Newcastle, United Kingdom

Location

Northumbria NHS Foundation Trust

North Shields, NE29 8NH, United Kingdom

Location

Churchill Hospital, Oxford University Hospitals NHS Foundation Trust

Oxford, United Kingdom

Location

Southampton General Hospital, University Hospital Southampton NHS Foundation Trust

Southampton, United Kingdom

Location

Royal Gwent Hospital, Aneurin Bevan University Health Board

Wales, United Kingdom

Location

Sandwell & West Birmingham

West Bromwich, B71 4HJ, United Kingdom

Location

MeSH Terms

Conditions

Bronchiectasis

Interventions

Saline Solution, Hypertonic; Carbocysteine

Condition Hierarchy (Ancestors)

Bronchial Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Hypertonic Solutions; Solutions; Pharmaceutical Preparations; Cysteine; Amino Acids, Sulfur; Sulfur Compounds; Organic Chemicals; Amino Acids, Dicarboxylic; Amino Acids; Amino Acids, Peptides, and Proteins

Study Officials

• J. Stuart Elborn

  Queen's University, Belfast

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: FACTORIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: A superiority, 2x2 factorial randomised open label trial with a 52-week follow-up period.

Study Record Dates

• First Submitted: May 17, 2019
• First Posted: October 25, 2019
• Study Start: June 27, 2018
• Primary Completion: September 30, 2024
• Study Completion: December 18, 2024
• Last Updated: May 2, 2025

Record last verified: 2025-01

Data Sharing

• IPD Sharing: Will not share

Locations

GB (20)