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We hypothesise that mucoactive agents (HTS or carbocisteine, or a combination) are effective in reducing exacerbations over a 52-week period, compared to usual care.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>This is a 52-week, 2\u2009\u00d7\u20092 factorial, randomized, open-label trial to determine the clinical effectiveness and cost effectiveness of HTS 6% and carbocisteine for airway clearance versus usual care - the Clinical and cost-effectiveness of hypertonic saline (HTS 6%) and carbocisteine for airway clearance versus usual care (CLEAR) trial. Patients will be randomised to (1) standard care and twice-daily nebulised HTS (6%), (2) standard care and carbocisteine (750\u2009mg three times per day until visit 3, reducing to 750\u2009mg twice per day), (3) standard care and combination of twice-daily nebulised HTS and carbocisteine, or (4) standard care. The primary outcome is the mean number of exacerbations over 52\u2009weeks. Key inclusion criteria are as follows: adults with a diagnosis of BE on computed tomography, BE as the primary respiratory diagnosis, and two or more pulmonary exacerbations in the last year requiring antibiotics and production of daily sputum.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>This trial\u2019s pragmatic research design avoids the significant costs associated with double-blind trials whilst optimising rigour in other areas of trial delivery. The CLEAR trial will provide evidence as to whether HTS, carbocisteine or both are effective and cost effective for patients with BE.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Trial registration<\/jats:title>\n                    <jats:p>EudraCT number: 2017-000664-14 (first entered in the database on 20 October 2017).<\/jats:p>\n                    <jats:p>\n                      ISRCTN.com,\n                      <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"http:\/\/www.isrctn.com\/ISRCTN89040295\">ISRCTN89040295<\/jats:ext-link>\n                      . Registered on 6 July\/2018.\n                    <\/jats:p>\n                    <jats:p>Funder: National Institute for Health Research, Health Technology Assessment Programme (15\/100\/01).<\/jats:p>\n                    <jats:p>Sponsor: Belfast Health and Social Care Trust.<\/jats:p>\n                    <jats:p>Ethics Reference Number: 17\/NE\/0339.<\/jats:p>\n                    <jats:p>Protocol version: v3.0 Final_14052018.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s13063-019-3766-9","type":"journal-article","created":{"date-parts":[[2019,12,19]],"date-time":"2019-12-19T04:04:20Z","timestamp":1576728260000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["A 2 \u00d7 2 factorial, randomised, 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\u2009weeks in adults with bronchiectasis: a protocol for the CLEAR clinical trial"],"prefix":"10.1186","volume":"20","author":[{"name":"On behalf of the CLEAR study group","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Judy Martina","family":"Bradley","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rohan","family":"Anand","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brenda","family":"O\u2019Neill","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kathryn","family":"Ferguson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mike","family":"Clarke","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mary","family":"Carroll","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James","family":"Chalmers","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anthony","family":"De Soyza","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jamie","family":"Duckers","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adam T.","family":"Hill","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael R.","family":"Loebinger","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fiona","family":"Copeland","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Evie","family":"Gardner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christina","family":"Campbell","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ashley","family":"Agus","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alistair","family":"McGuire","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roisin","family":"Boyle","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fionnuala","family":"McKinney","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naomi","family":"Dickson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Danny F.","family":"McAuley","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stuart","family":"Elborn","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2019,12,19]]},"reference":[{"issue":"4","key":"3766_CR1","doi-asserted-by":"publisher","first-page":"955","DOI":"10.1378\/chest.108.4.955","volume":"108","author":"MB Nicotra","year":"1995","unstructured":"Nicotra MB, Rivera M, Dale AM, Shepherd R, Carter R. 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Central ethical approval has been confirmed from the North East - Tyne & Wear South Research Ethics Committee (ref approval no. 17\/NE\/0339) and recruitment will not begin until management permission is confirmed from all NHS organisations involved in the study in accordance with NHS research governance arrangements. The trial is being conducted in accordance with Good Clinical Practice and the Declaration of Helsinki. Informed consent is obtained from each participant in writing before completing any trial-related assessments or interventions.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare that they have no competing interests.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"747"}}