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

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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