TY - JOUR
T1 - A 2 × 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 weeks in adults with bronchiectasis
T2 - a protocol for the CLEAR clinical trial
AU - Bradley, Judy Martina
AU - Anand, Rohan
AU - O'Neill, Brenda
AU - Ferguson, Kathryn
AU - Clarke, Mike
AU - Carroll, Mary
AU - Chalmers, James
AU - De Soyza, Anthony
AU - Duckers, Jamie
AU - Hill, Adam T.
AU - Loebinger, Michael R.
AU - Copeland, Fiona
AU - Gardner, Evie
AU - Campbell, Christina
AU - Agus, Ashley
AU - McGuire, Alistair
AU - Boyle, Roisin
AU - McKinney, Fionnuala
AU - Dickson, Naomi
AU - McAuley, Danny F.
AU - Elborn, Stuart
N1 - This study is funded by the National Institute for Health Research (NIHR) Health Technology Assessment (HTA) Programme (15/100/01). PARI will also provide non-financial support to this study through the provision of HTS 6%, eFlow nebuliser systems with eTrack controller, mySpirosense lung function devices for home use and associated technology for processing and accessing collected data.
PY - 2019/12/19
Y1 - 2019/12/19
N2 - Background: Current guidelines for the management of bronchiectasis (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. 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.Methods: This is a 52-week, 2 × 2 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 mg three times per day until visit 3, reducing to 750 mg 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 weeks. 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.Discussion: This trial's 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.Trial registration: EudraCT number: 2017-000664-14 (first entered in the database on 20 October 2017). ISRCTN.com, ISRCTN89040295. Registered on 6 July/2018.
AB - Background: Current guidelines for the management of bronchiectasis (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. 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.Methods: This is a 52-week, 2 × 2 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 mg three times per day until visit 3, reducing to 750 mg 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 weeks. 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.Discussion: This trial's 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.Trial registration: EudraCT number: 2017-000664-14 (first entered in the database on 20 October 2017). ISRCTN.com, ISRCTN89040295. Registered on 6 July/2018.
KW - Clinical trial protocol
KW - Factorial design
KW - Bronchiectasis
KW - Hypertonic saline
KW - Carbocisteine
KW - Exacerbation
KW - SWAT
U2 - 10.1186/s13063-019-3766-9
DO - 10.1186/s13063-019-3766-9
M3 - Article
C2 - 31856887
SN - 1745-6215
VL - 20
JO - Trials
JF - Trials
M1 - 747
ER -