Effectiveness of mucoactives (carbocisteine and hypertonic saline) in addition to usual airway clearance management with usual airway clearance management alone in acute respiratory failure (MARCH): study protocol for a multi-centre 2x2 factorial, randomised, controlled, open-label, Phase 3, pragmatic, clinical and cost-effectiveness trial with internal pilot [version 1; peer review: 2 approved]
Background Usual airway clearance management in critically ill patients with acute respiratory failure includes suctioning, humidification, use of isotonic saline, and respiratory physiotherapy techniques. Escalation to use of mucoactives occurs when secretions are difficult to clear. Use of mucoact...
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| author | Mike Clarke Marc Chikhani Cliona McDowell Ranjit Lall Michael McKelvey Margaret McFarland Brenda O'Neill Cecilia O'Kane Murali Shyamsundar Gavin Perkins Clifford C Taggart Gordon Sturmey Barry Williams John Warburton Paul Dark Bronwen Connolly Ashley Agus Naomi Dickson Mark Borthwick Bronagh Blackwood Daniel F McAuley Christina Campbell Judy Bradley |
| author_facet | Mike Clarke Marc Chikhani Cliona McDowell Ranjit Lall Michael McKelvey Margaret McFarland Brenda O'Neill Cecilia O'Kane Murali Shyamsundar Gavin Perkins Clifford C Taggart Gordon Sturmey Barry Williams John Warburton Paul Dark Bronwen Connolly Ashley Agus Naomi Dickson Mark Borthwick Bronagh Blackwood Daniel F McAuley Christina Campbell Judy Bradley |
| author_sort | Mike Clarke |
| collection | DOAJ |
| description | Background Usual airway clearance management in critically ill patients with acute respiratory failure includes suctioning, humidification, use of isotonic saline, and respiratory physiotherapy techniques. Escalation to use of mucoactives occurs when secretions are difficult to clear. Use of mucoactives in clinical practice for this patient population is extensive, yet empirical and variable. Carbocisteine and hypertonic saline are the most used agents, but evidence for their effectiveness is absent or minimal. The lack of existing large-scale randomised trials comparing mucoactives to usual airway clearance management alone in critically ill patients with acute respiratory failure highlights the urgency and necessity of this study. Aim To determine whether the use of mucoactives in critically ill patients with acute respiratory failure improves clinical outcomes and is cost effective, compared to usual airway clearance management alone. Methods A UK multi-centre, 2x2 factorial, randomised, controlled, open-label, Phase 3, pragmatic, clinical and cost effectiveness trial with internal pilot. The target sample is 1956 critically ill adults. Participants will be equally allocated across four trial arms. All participants will receive usual airway clearance management. In three intervention groups, participants will receive either carbocisteine, hypertonic saline, or a combination of carbocisteine and hypertonic saline. In the fourth comparator group, participants will receive usual airway clearance management alone. The primary outcome is the duration of mechanical ventilation with secondary clinical, safety, and health resource utilisation outcomes. The trial will be reported in accordance with CONSORT guidelines. Ethical approval was granted by Leeds East (Yorkshire & The Humber) Research Ethics Committee (reference 21/YH/0234) on 28th October 2021. All participants will provide written, informed consent via either Personal or Professional Legal Representatives, and subsequently directly once capacity is regained. Trial registration Main trial: ISRCTN17683568, https://www.isrctn.com/ISRCTN17683568, 25th November 2021 Study Within A Trial: ISRCTN16675252, https://www.isrctn.com/ISRCTN16675252, 3rd November 2021 EudraCT Number, 2021-003763-94 |
| format | Article |
| id | doaj-art-63451043aa6a4ac9a88fbefa8b7672c0 |
| institution | Kabale University |
| issn | 2633-4402 |
| language | English |
| publishDate | 2025-04-01 |
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| spelling | doaj-art-63451043aa6a4ac9a88fbefa8b7672c02025-08-20T03:44:54ZengF1000 Research LtdNIHR Open Research2633-44022025-04-01510.3310/nihropenres.13905.115112Effectiveness of mucoactives (carbocisteine and hypertonic saline) in addition to usual airway clearance management with usual airway clearance management alone in acute respiratory failure (MARCH): study protocol for a multi-centre 2x2 factorial, randomised, controlled, open-label, Phase 3, pragmatic, clinical and cost-effectiveness trial with internal pilot [version 1; peer review: 2 approved]Mike Clarke0Marc Chikhani1Cliona McDowell2Ranjit Lall3Michael McKelvey4Margaret McFarland5Brenda O'Neill6https://orcid.org/0000-0002-6471-1413Cecilia O'Kane7Murali Shyamsundar8Gavin Perkins9Clifford C Taggart10Gordon Sturmey11Barry Williams12John Warburton13Paul Dark14Bronwen Connolly15https://orcid.org/0000-0002-5676-5497Ashley Agus16Naomi Dickson17Mark Borthwick18https://orcid.org/0000-0002-3249-1508Bronagh Blackwood19https://orcid.org/0000-0002-4583-5381Daniel F McAuley20Christina Campbell21Judy Bradley22Northern Ireland Clinical Trials Unit, Belfast, Northern Ireland, UKUniversity of Nottingham, Nottingham, England, UKNorthern Ireland Clinical Trials Unit, Belfast, Northern Ireland, UKUniversity of Warwick Warwick Clinical Trials Unit, Coventry, England, UKWellcome-Wolfson Institute for Experimental Medicine, Queen's University Belfast, Belfast, Northern Ireland, UKPharmacy Department, Royal Victoria Hospital, Belfast, Northern Ireland, UKInstitute of Nursing and Health Research, Ulster University, Coleraine, Northern Ireland, UKWellcome-Wolfson Institute for Experimental Medicine, Queen's University Belfast, Belfast, Northern Ireland, UKRegional Intensive Care Unit, Royal Victoria Hospital, Belfast, Northern Ireland, UKWarwick Clinical Trials Unit, University of Warwick, Coventry, England, UKWellcome-Wolfson Institute for Experimental Medicine, Queen's University Belfast, Belfast, Northern Ireland, UKIndependent Patient Partner, England, UKIndependent Patient Partner, England, UKUniversity Hospitals Bristol NHS Foundation Trust, Bristol, England, UKDivision of Immunology, Immunity to Infection and Respiratory Medicine, The University of Manchester, Manchester, England, UKWellcome-Wolfson Institute for Experimental Medicine, Queen's University Belfast, Belfast, Northern Ireland, UKNorthern Ireland Clinical Trials Unit, Belfast, Northern Ireland, UKNorthern Ireland Clinical Trials Unit, Belfast, Northern Ireland, UKOxford University Hospitals NHS Foundation Trust, Oxford, England, UKWellcome-Wolfson Institute for Experimental Medicine, Queen's University Belfast, Belfast, Northern Ireland, UKWellcome-Wolfson Institute for Experimental Medicine, Queen's University Belfast, Belfast, Northern Ireland, UKNorthern Ireland Clinical Trials Unit, Belfast, Northern Ireland, UKWellcome-Wolfson Institute for Experimental Medicine, Queen's University Belfast, Belfast, Northern Ireland, UKBackground Usual airway clearance management in critically ill patients with acute respiratory failure includes suctioning, humidification, use of isotonic saline, and respiratory physiotherapy techniques. Escalation to use of mucoactives occurs when secretions are difficult to clear. Use of mucoactives in clinical practice for this patient population is extensive, yet empirical and variable. Carbocisteine and hypertonic saline are the most used agents, but evidence for their effectiveness is absent or minimal. The lack of existing large-scale randomised trials comparing mucoactives to usual airway clearance management alone in critically ill patients with acute respiratory failure highlights the urgency and necessity of this study. Aim To determine whether the use of mucoactives in critically ill patients with acute respiratory failure improves clinical outcomes and is cost effective, compared to usual airway clearance management alone. Methods A UK multi-centre, 2x2 factorial, randomised, controlled, open-label, Phase 3, pragmatic, clinical and cost effectiveness trial with internal pilot. The target sample is 1956 critically ill adults. Participants will be equally allocated across four trial arms. All participants will receive usual airway clearance management. In three intervention groups, participants will receive either carbocisteine, hypertonic saline, or a combination of carbocisteine and hypertonic saline. In the fourth comparator group, participants will receive usual airway clearance management alone. The primary outcome is the duration of mechanical ventilation with secondary clinical, safety, and health resource utilisation outcomes. The trial will be reported in accordance with CONSORT guidelines. Ethical approval was granted by Leeds East (Yorkshire & The Humber) Research Ethics Committee (reference 21/YH/0234) on 28th October 2021. All participants will provide written, informed consent via either Personal or Professional Legal Representatives, and subsequently directly once capacity is regained. Trial registration Main trial: ISRCTN17683568, https://www.isrctn.com/ISRCTN17683568, 25th November 2021 Study Within A Trial: ISRCTN16675252, https://www.isrctn.com/ISRCTN16675252, 3rd November 2021 EudraCT Number, 2021-003763-94https://openresearch.nihr.ac.uk/articles/5-30/v1Acute respiratory failure critical illness randomised controlled trial factorial carbocisteine hypertonic salineeng |
| spellingShingle | Mike Clarke Marc Chikhani Cliona McDowell Ranjit Lall Michael McKelvey Margaret McFarland Brenda O'Neill Cecilia O'Kane Murali Shyamsundar Gavin Perkins Clifford C Taggart Gordon Sturmey Barry Williams John Warburton Paul Dark Bronwen Connolly Ashley Agus Naomi Dickson Mark Borthwick Bronagh Blackwood Daniel F McAuley Christina Campbell Judy Bradley Effectiveness of mucoactives (carbocisteine and hypertonic saline) in addition to usual airway clearance management with usual airway clearance management alone in acute respiratory failure (MARCH): study protocol for a multi-centre 2x2 factorial, randomised, controlled, open-label, Phase 3, pragmatic, clinical and cost-effectiveness trial with internal pilot [version 1; peer review: 2 approved] NIHR Open Research Acute respiratory failure critical illness randomised controlled trial factorial carbocisteine hypertonic saline eng |
| title | Effectiveness of mucoactives (carbocisteine and hypertonic saline) in addition to usual airway clearance management with usual airway clearance management alone in acute respiratory failure (MARCH): study protocol for a multi-centre 2x2 factorial, randomised, controlled, open-label, Phase 3, pragmatic, clinical and cost-effectiveness trial with internal pilot [version 1; peer review: 2 approved] |
| title_full | Effectiveness of mucoactives (carbocisteine and hypertonic saline) in addition to usual airway clearance management with usual airway clearance management alone in acute respiratory failure (MARCH): study protocol for a multi-centre 2x2 factorial, randomised, controlled, open-label, Phase 3, pragmatic, clinical and cost-effectiveness trial with internal pilot [version 1; peer review: 2 approved] |
| title_fullStr | Effectiveness of mucoactives (carbocisteine and hypertonic saline) in addition to usual airway clearance management with usual airway clearance management alone in acute respiratory failure (MARCH): study protocol for a multi-centre 2x2 factorial, randomised, controlled, open-label, Phase 3, pragmatic, clinical and cost-effectiveness trial with internal pilot [version 1; peer review: 2 approved] |
| title_full_unstemmed | Effectiveness of mucoactives (carbocisteine and hypertonic saline) in addition to usual airway clearance management with usual airway clearance management alone in acute respiratory failure (MARCH): study protocol for a multi-centre 2x2 factorial, randomised, controlled, open-label, Phase 3, pragmatic, clinical and cost-effectiveness trial with internal pilot [version 1; peer review: 2 approved] |
| title_short | Effectiveness of mucoactives (carbocisteine and hypertonic saline) in addition to usual airway clearance management with usual airway clearance management alone in acute respiratory failure (MARCH): study protocol for a multi-centre 2x2 factorial, randomised, controlled, open-label, Phase 3, pragmatic, clinical and cost-effectiveness trial with internal pilot [version 1; peer review: 2 approved] |
| title_sort | effectiveness of mucoactives carbocisteine and hypertonic saline in addition to usual airway clearance management with usual airway clearance management alone in acute respiratory failure march study protocol for a multi centre 2x2 factorial randomised controlled open label phase 3 pragmatic clinical and cost effectiveness trial with internal pilot version 1 peer review 2 approved |
| topic | Acute respiratory failure critical illness randomised controlled trial factorial carbocisteine hypertonic saline eng |
| url | https://openresearch.nihr.ac.uk/articles/5-30/v1 |
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