Randomised, sham-controlled, double-blinded, multicentre international trial to evaluate the efficacy of the Ventfree Respiratory Muscle Stimulator to assist ventilator weaning in critically ill patients: a study protocol of a randomised controlled trial.

introductionNearly 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. METHODS AND ANALYSIS: 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. ETHICS AND DISSEMINATION: 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:Ethics committee: Comité de Protection des Personnes Ile-de-France X.Reference numbers: CPP 27-2024; RCB 2024-A00559-38.Initial approval date: 14 May 2024.Australia:Ethics committee: South Eastern Sydney Local Health District Human Research Ethics Committee.Reference number: 2022/ETH02724.Initial approval date: 21 March 2023.Netherlands:Ethics committee: Medisch Ethische Toetsings Commissie Erasmus MC.Reference numbers: MEC-2023-0364; NL84195.000.23.Initial approval date: 30 April 2024.USA:Ethics committee: WCG IRB.IRB tracking number: 20214073.Initial approval date: 13 March 2023.All participating sites are currently approved and operating under protocol version 09 or later. TRIAL REGISTRATION NUMBER: NCT05759013. Registered 8 March 2023.