The MARCH (mucoactives in acute respiratory failure) trial has shown that two drugs widely used across the world to help airway clearance in critically ill patients on mechanical ventilation are not effective. The trial, involving 71 UK hospitals, was funded by the National Institute for Health and Care Research (NIHR) and led by Queen’s University Belfast.
The findings from MARCH have been published in the New England Journal of Medicine and were presented at the Critical Care Reviews Meeting 2026 in Belfast.
Acute respiratory failure in the critically ill is the commonest cause for patients requiring mechanical ventilation in the intensive care unit (ICU).
However, invasive mechanical ventilation used to treat respiratory failure can cause airway secretions to build up because it disrupts the lungs’ natural clearing system and changes the amount and thickness of secretions.
The two drugs investigated in the study were carbocisteine and hypertonic saline. Both drugs are commonly used in ICUs across the world to aid airway clearance and had been thought to help reduce the length of time patients require mechanical ventilation.
The research team looked at nearly 2,000 patients recruited from the 71 sites across the UK. The patients were critically ill with acute respiratory failure and thick airway secretions (phlegm) receiving mechanical ventilation. The research team wanted to see how effective the two drugs were at shortening the time patients spent on mechanical ventilation.
They compared carbocisteine versus hypertonic saline, in combination and with usual care.
The MARCH study team found that neither drug reduced the amount of time patients spent on mechanical ventilation, but both drugs caused harm in a very small number of patients. They saw an increased risk of:
- Gastrointestinal bleeding in 1.4% of patients given carbocisteine
- Bronchoconstriction (asthma like breathing) in 2.4% of patients given hypertonic saline
These harms were only identified thanks to the study.
The BRI ICU team plan to stop routine use of these drugs on the strength of this evidence.
Professor Bronwen Connolly, Chief Investigator for the trial from the Wellcome-Wolfson Institute for Experimental Medicine at Queen’s University Belfast, explains:
“Through this trial, we aimed to improve patient care and clinical practice by understanding whether these two drugs are helpful for critically ill patients receiving mechanical ventilation.
“Our findings show that the addition of carbocisteine or hypertonic saline in critically ill patients with acute respiratory failure showed no benefit, and both drugs were associated with harm, highlighting the need for caution in their use in clinical practice.”
Ema Swingwood, Consultant Therapist and Research Physiotherapist at the Bristol Royal Infirmary ICU said:
“These are landmark findings that will change how ICU patients are managed in the future. They open the door to further research into physiotherapy-led airway clearance strategies and their role in improving patient care.”
Jeremy Bewley, Consultant in Intensive Care and Anaesthesia and research lead for the MARCH trial at the Bristol Royal Infirmary, said:
“This study will change clinical practice, helping thousands of patients while saving the NHS more than £100,000 per year. I need to thank the critically ill patients and their families who agreed to participate in this vital research. It is only through studies like this that effective or ineffective treatments can be identified, which benefits all of us.”
The research team comprised multi-professional experts across critical care medicine, physiotherapy, pharmacy, and nursing, with world class expertise in the delivery of clinical trials to critically ill patients with acute respiratory failure. The trial was managed by the Northern Ireland Clinical Trials Unit.
The research was also supported by the Health and Social Care Research & Development Division (HSC R&D Division) of the Public Health Agency through the Northern Ireland Clinical Research Network and Clinical Trials Unit
Read the paper
Carbocisteine or Hypertonic Saline for Acute Respiratory Failure
Bronwen Connolly et al, published in the New England Journal of Medicine