Nearly half of patients who receive invasive mechanical ventilation for acute respiratory failure require over 4 days of ventilator support, each day of which is associated with increased morbidity, mortality and cost. Many of these patients develop expiratory muscle atrophy and weakness, which are linked to failed extubation and weaning. We seek to test the hypothesis that exhalation synchronised abdominal functional electrical stimulation reduces mechanical ventilation duration.

This pivotal superiority trial will be performed in up to 30 intensive care units (ICUs) in the USA, France, the Netherlands and Australia. Adults (≥22 years old) who have been mechanically ventilated for 24–96 hours and are expected to remain ventilated for another 24+ hours are potentially eligible. We will recruit participants until 150 successful liberations from mechanical ventilation occur. To achieve this, we estimate that a maximum of 272 participants will be randomised in a 1:1 ratio to receive 30 min of active exhalation synchronised abdominal functional electrical stimulation (vs sham). The intervention will be applied using the VentFree Respiratory Muscle Stimulator two times per day, a minimum of 5 days per week, for a maximum of 28 days or until ICU discharge. The primary outcome is time from first intervention to successful liberation from mechanical ventilation. Secondary outcomes include cough peak flow (CPF) and maximum expiratory pressure (MEP) at 24 hours post-extubation, hospital and ICU length of stay, reintubations, complications, ICU readmissions, 90-day mortality and quality of life. The participant, clinical team and outcome assessor are blinded to group allocation. A positive outcome has the potential to improve patient-centred outcomes in ICUs.

This study was approved by local ethics institutions in the USA, Australia, France and the Netherlands. We describe the methods herein using the Standard Protocol Items for Randomised Trials framework and discuss key design decisions. The results will be disseminated through peer-reviewed journal publications, conference presentations and clinicaltrials.gov updates. Individual country-level approvals are as follows:

France:

Australia:

Netherlands:

USA:

All participating sites are currently approved and operating under protocol version 09 or later.

NCT05759013. Registered 8 March 2023.