Neurally adjusted ventilatory assist in the adult critical care unit: A randomized, parallel group, allocation concealed, controlled, open, phase 3 pragmatic clinical and cost effectiveness trial with internal pilot

BACKGROUND Usual ventilator weaning involves the manual adjustment of support settings, which often means treatment is not matched to patient need, resulting in extended duration of ventilation and worse patient outcomes. In contrast, innovative automated ventilation systems such as Neurally Adjusted Ventilatory Assist (NAVA), adapt the ventilator support automatically according to physiological parameters. In NAVA, the activity of the diaphragm muscle is used as a monitor of respiratory drive, and to deliver proportional pressure support in synchrony with a patient'Äôs changing ventilatory need. RESEARCH QUESTION What is the clinical and cost-effectiveness of Neurally Adjusted Ventilatory Assist for patients at risk of extended mechanical ventilation duration? DESIGN A multi-centre randomised, allocation concealed, controlled, open label, phase 3 pragmatic clinical and cost effectiveness trial with an internal pilot SETTING Participants will be recruited in at least 40 adult ICUs across the UK to maximise the generalisability of findings TARGET POPULATION Critically ill adults at risk of extended durations of mechanical ventilation support INCLUSION CRITERIA Adults considered by the ICU clinical team likely to remain intubated and ventilated for >48 hours, with a diagnosis of one or a combination of - Chronic Obstructive Pulmonary Disease - Left and/or right ventricular heart failure - Acute Respiratory Distress Syndrome - Pneumonia including COVID-19 - Acute Kidney Injury EXCLUSION CRITERIA - Imminent death or treatment withdrawal - Contraindication to NAVA feeding tube insertion - Known or suspected portal hypertension - Neurological cause of ventilator dependence (e.g., brain injury / neuromuscular disease) - Domiciliary mechanical ventilation PRIMARY OUTCOME Duration of mechanical ventilation, defined as time from randomisation until first successful unassisted breathing SECONDARY OUTCOMES IN HOSPITAL: Re-intubation; Duration of ICU and hospital stay; Mortality; Adverse events AT 60 DAYS: Health-related quality of life; Mortality AT 6 MONTHS: Health-related quality of life; Mortality; Health service use HEALTH ECONOMIC EVALUATION Cost-effectiveness will be compared at 6 months via a cost-utility analysis from the perspective of the NHS and personal social services SAMPLE SIZE 900 patients TIMELINE Allowing 6 months for approvals and set-up of 10 sites, and a realistic staggered set-up of the remaining 30 sites, the total recruitment duration is 39 months. With follow-up, analysis and reporting, the total grant duration is 53 months EXPERTISE To optimise all aspects of trial delivery, our multiprofessional team includes clinical trialists, physician and nurse national leaders in critical care, clinical experts, physiologists, methodologists, statisticians, health economists, and former patients and family representatives with lived experience of prolonged mechanical ventilation treatment. ANTICIPATED IMPACT AND DISSEMINATION Dissemination will take multiple routes including publication in international high impact factor journals, presentation at relevant national and international conferences, circulation via relevant patient and family networks, and via social media channels. We anticipate significant impact to patients and clinical practice.