Rest Or Moderate Mechanical Ventilation During ECMO Support - ROMEO

Research question: What is the clinical efficacy of near apnoeic ventilation (NAV) with two sigh breaths per minute after initiation of extracorporeal membrane oxygenation (ECMO) for acute respiratory distress syndrome (ARDS), in comparison with standard lung protective ventilation of 10-20 breaths per minute.

Background: Acute respiratory distress syndrome (ARDS) is characterised by life-threatening respiratory failure requiring invasive mechanical ventilation (IMV). ARDS patients that continue to have severe lung failure despite maximal IMV often require veno-venous ECMO, as they are prone to ventilator-associated lung injury (VILI). ECMO uses an artificial membrane lung to take over gas exchange and enables significant reductions in ventilator pressures and volumes, thereby reducing VILI.

NAV is a strategy that combines two physiological concepts: 1) lung rest and 2) short cyclic alveolar recruitment manoeuvres (or sigh breaths). Lung rest maximally mitigates VILI whilst sigh breaths prevent lung collapse. We hypothesise that through these mechanisms a NAV strategy is associated with faster lung recovery leading to a reduction in duration of ECMO, ventilation and ICU stay.

Aims and objectives: To investigate the clinical efficacy of NAV with two sigh breaths compared to conventional IMV set at 10-20 breaths per minute in ARDS patients supported on ECMO. The primary objective is to conduct a multi-centre, parallel group randomised controlled trial to investigate the potential of NAV to reduce ECMO duration following randomisation as compared to usual care.

Secondary objectives are to determine: 1) all-cause mortality at 60 days, 6 months, and 1-year; 2) time to first successful extubation; 3) duration of invasive mechanical ventilation; 4) serious adverse events to hospital discharge (including AEs of specific interest related to ECMO); 5) and duration of ICU and hospital stay.

Methods: Three-stage group-sequential, two-arm, parallel-group, multi-centre, open-label, individually randomised controlled trial with a sample-size re-estimation adaptive approach incorporating two planned interim analyses at 40% and 60% of the observed events, followed by a final analysis and a 6-month internal pilot.

Inclusion criteria includes patients with an acute and potentially reversible cause of ARDS as determined by the treating physician undergoing Invasive mechanical ventilation and receiving ECMO for severe ARDS. Exclusion criteria includes those that decline consent; have had ECMO initiated for >48 hours from ECMO initiation, and if the patient is likely to die or withdrawal of life sustaining therapy within 48 hours of randomisation.

Timelines for delivery: We anticipate 6 months for set up (training and site initiation) across all 10 UK ECMO sites with a 39-month recruitment window (covering 3 full winter seasons, optimising feasibility), enabling a 12-month follow-up concluding with a 3-month close-out.

Dissemination: In collaboration with our PPI partners, we plan to undertake a broad public engagement including a trial website, lay versions of infographic style information sheets, and reports to increase accessibility of our findings. We will also present the results through international ECMO and critical care scientific conferences and in papers in medical journals.

Further engagement with NHS highly specialist commissioners and the Extracorporeal Life Support Organisation will enable national/global dissemination and implementation.