Hypertonic saline or carbocisteine in bronchiectasis.
Abstract
BACKGROUND: Bronchiectasis guidelines are inconsistent with regard to the effectiveness of mucoactive agents, and their use varies geographically. Large trials are needed to assess safety and effectiveness.
METHODS: For this open-label, randomized, two-by-two factorial trial at 20 sites in the United Kingdom, we enrolled participants with non-cystic fibrosis bronchiectasis who had frequent pulmonary exacerbations and daily sputum production. Current smokers and persons who had recently received mucoactive treatments were excluded. All participants received standard care and were also assigned either to one of three mucoactive-drug groups - hypertonic saline (the hypertonic-saline group), hypertonic saline and carbocisteine (the combination group), or carbocisteine (the carbocisteine group) - or to standard care alone. The comparisons were between hypertonic saline and no hypertonic saline and between carbocisteine and no carbocisteine, with each category consisting of two groups. The primary outcome was the number of pulmonary exacerbations over a 52-week period. Key secondary outcomes were scores on disease-specific health-related quality-of-life assessments, time to next pulmonary exacerbation, and safety.
RESULTS: A total of 288 participants underwent randomization. No treatment interactions were found. The mean number of adjudicated fully qualifying pulmonary exacerbations over the 52-week period was 0.76 (95% confidence interval [CI], 0.58 to 0.95) with hypertonic saline as compared with 0.98 (95% CI, 0.78 to 1.19) with no hypertonic saline (adjusted between-group difference in the means, -0.25 [95% CI, -0.57 to 0.07; Pā=ā0.12]) and 0.86 (95% CI, 0.66 to 1.06) with carbocisteine as compared with 0.90 (95% CI, 0.70 to 1.09) with no carbocisteine (adjusted between-group difference in the means, -0.04 [95% CI, -0.36 to 0.28; Pā=ā0.81]). Secondary outcomes and the incidence of adverse events, including serious adverse events, were similar across the groups.
CONCLUSIONS: In participants with bronchiectasis, neither hypertonic saline nor carbocisteine significantly reduced the mean incidence of pulmonary exacerbations over a period of 52 weeks. (Funded by the National Institute for Health and Care Research Health Technology Assessment Programme and others; ISRCTN Registry number, ISRCTN89040295.).
Author
Bradley, Judy M
O'Neill, Brenda
McAuley, Daniel F
Chalmers, James D
De Soyza, Anthony
Hill, Adam T
Carroll, Mary
Loebinger, Michael R
Duckers, Jamie
Clarke, Mike
McLeese, Rebecca H
Ferguson, Kathryn
Jackson, Andrew
Campbell, Christina
McDowell, ClĆona
Agus, Ashley
Norrie, John
Copeland, Fiona
Downey, Damian G
Convery, Rory
Kelly, Martin
Flight, William
Talbot, Nick P
Hurst, John R
Steer, John
Anwar, Muhammad
Shahidi, Mitra
Gatheral, Timothy
Etumi, Mohamed
Sullivan, Anita L
Ionescu, Andreea Alina
Patil, Veeresh
Bhattacharya, Milan
Caskey, Steven
Cosgrove, Denise
Hagan, Conor
Shoemark, Amelia
McManus, Terence
Davies, Gareth
Elborn, J Stuart
O'Neill, Brenda
McAuley, Daniel F
Chalmers, James D
De Soyza, Anthony
Hill, Adam T
Carroll, Mary
Loebinger, Michael R
Duckers, Jamie
Clarke, Mike
McLeese, Rebecca H
Ferguson, Kathryn
Jackson, Andrew
Campbell, Christina
McDowell, ClĆona
Agus, Ashley
Norrie, John
Copeland, Fiona
Downey, Damian G
Convery, Rory
Kelly, Martin
Flight, William
Talbot, Nick P
Hurst, John R
Steer, John
Anwar, Muhammad
Shahidi, Mitra
Gatheral, Timothy
Etumi, Mohamed
Sullivan, Anita L
Ionescu, Andreea Alina
Patil, Veeresh
Bhattacharya, Milan
Caskey, Steven
Cosgrove, Denise
Hagan, Conor
Shoemark, Amelia
McManus, Terence
Davies, Gareth
Elborn, J Stuart
Date
2025-09-28
Type
Article
Subject
Bronchiectasis, Saline solution, hypertonic
Collections
Citation
Bradley JM, O'Neill B, McAuley DF, Chalmers JD, De Soyza A, Hill AT, Carroll M, Loebinger MR, Duckers J, Clarke M, McLeese RH, Ferguson K, Jackson A, Campbell C, McDowell C, Agus A, Norrie J, Copeland F, Downey DG, Convery R, Kelly M, Flight W, Talbot NP, Hurst JR, Steer J, Anwar M, Shahidi M, Gatheral T, Etumi M, Sullivan AL, Ionescu AA, Patil V, Bhattacharya M, Caskey S, Cosgrove D, Hagan C, Shoemark A, McManus T, Davies G, Elborn JS; CLEAR Investigator Team. Hypertonic Saline or Carbocisteine in Bronchiectasis. N Engl J Med. 2025 Oct 23;393(16):1565-1577. doi: 10.1056/NEJMoa2510095. Epub 2025 Sep 28.
Journal / Source Title
The New England Journal of Medicine
DOI
10.1056/NEJMoa2510095
PMID
41020514
Publisher
Massachusetts Medical Society
Publisherās URL
https://www.nejm.org/medical-index