Brief Title
Randomised Open Label Trial of Hypertonic Saline and Carbocisteine in Bronchiectasis (CLEAR)
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
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.
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.
Study Phase
Phase 3
Study Type
Interventional
Primary Outcome
Mean Number of Exacerbations
Secondary Outcome
Disease-Specific Health-Related Quality of Life
Condition
Bronchiectasis
Intervention
Hypertonic saline
Study Arms / Comparison Groups
Standard Care and HTS
Description: 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).
Publications
* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.
Recruitment Information
Recruitment Status
Drug
Estimated Enrollment
380
Start Date
June 27, 2018
Completion Date
August 31, 2022
Primary Completion Date
August 31, 2021
Eligibility Criteria
Inclusion Criteria:
- Diagnosis of BE on high resolution computed tomography(HRCT)/computed tomography (CT)
scans
- BE must be the primary respiratory diagnosis
- Two 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
Gender
All
Ages
18 Years - N/A
Accepts Healthy Volunteers
No
Contacts
J. Stuart Elborn, 028 90 635794, [email protected]
Location Countries
United Kingdom
Location Countries
United Kingdom
Administrative Informations
NCT ID
NCT04140214
Organization ID
16178SE-AS
Responsible Party
Sponsor
Study Sponsor
Belfast Health and Social Care Trust
Collaborators
Queen's University, Belfast
Study Sponsor
J. Stuart Elborn, Principal Investigator, Queen's University, Belfast
Verification Date
October 2019