在急性呼吸衰竭中，黏液促排剂（羧甲司坦和高渗盐水）联合常规气道清理管理与单纯常规气道清理管理相比的有效性（MARCH）：一项多中心2×2析因、随机、对照、开放标签、3期、实用、临床及成本效益试验（含内部预试验）的研究方案

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.

作者信息

Connolly Bronwen, Dickson Naomi, Agus Ashley, Blackwood Bronagh, Borthwick Mark, Bradley Judy, Campbell Christina, Chikhani Marc, Clarke Mike, Dark Paul, Lall Ranjit, McDowell Cliona, McFarland Margaret, McKelvey Michael, O'Kane Cecilia, O'Neill Brenda, Perkins Gavin, Shyamsundar Murali, Sturmey Gordon, Taggart Clifford C, Warburton John, Williams Barry, McAuley Daniel F

机构信息

Wellcome-Wolfson Institute for Experimental Medicine, Queen's University Belfast, Belfast, Northern Ireland, UK.

Department of Physiotherapy, The University of Melbourne, Melbourne, Victoria, Australia.

出版信息

NIHR Open Res. 2025 Apr 10;5:30. doi: 10.3310/nihropenres.13905.1. eCollection 2025.

DOI:10.3310/nihropenres.13905.1

PMID:40519627

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12163365/

Abstract

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 28 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, 25 November 2021Study Within A Trial: ISRCTN16675252, https://www.isrctn.com/ISRCTN16675252, 3 November 2021EudraCT Number, 2021-003763-94.

摘要

背景

急性呼吸衰竭重症患者的常规气道清理管理包括吸痰、湿化、使用等渗盐水以及呼吸物理治疗技术。当分泌物难以清除时，会升级使用黏液溶解剂。黏液溶解剂在该患者群体的临床实践中使用广泛，但多为经验性且使用情况不一。羧甲司坦和高渗盐水是最常用的药物，但关于其有效性的证据缺乏或极少。目前缺乏在急性呼吸衰竭重症患者中比较黏液溶解剂与单纯常规气道清理管理的大规模随机试验，这凸显了本研究的紧迫性和必要性。

目的

与单纯常规气道清理管理相比，确定在急性呼吸衰竭重症患者中使用黏液溶解剂是否能改善临床结局并具有成本效益。

方法

一项英国多中心、2×2析因、随机、对照、开放标签、3期、务实的临床及成本效益试验，并设有内部预试验。目标样本为1956名成年重症患者。参与者将被平均分配到四个试验组。所有参与者都将接受常规气道清理管理。在三个干预组中，参与者将分别接受羧甲司坦、高渗盐水或羧甲司坦与高渗盐水的联合治疗。在第四个对照组中，参与者将仅接受常规气道清理管理。主要结局是机械通气时间，次要结局包括临床、安全性及卫生资源利用方面的结局。试验将按照CONSORT指南报告。2021年10月28日，利兹东部（约克郡及亨伯赛德）研究伦理委员会（参考编号21/YH/0234）批准了伦理许可。所有参与者将通过个人或专业法定代表人提供书面知情同意书，恢复行为能力后将直接再次提供同意书。