RELEASE Overview

Study Summary

RELEASE is a a multi-centre, pragmatic, individual patient randomised, open-label, parallel group study to evaluate the clinical- and cost-effectiveness of Airway Pressure Release Ventilation (APRV) in adults with acute hypoxemic respiratory failure (AHRF)

Hospitalised adult patients with AHRF will be randomised in a 1:1 ratio to either APRV or standard care. The study will include an internal pilot (8 months duration) during which we will test the detailed trial procedures, data collection and confirm the feasibility of recruitment. Patients will be followed up at 2 and 6 months post-randomisation to assess their quality of life and to collect cost data for the economic evaluation.

The trial will be conducted across 40 hospitals in the UK.

Primary Objective

The primary objective of the study is to investigate the clinical and cost effectiveness of early APRV compared to conventional lung protective invasive mechanical ventilation (IMV) in patients with moderate-severe AHRF.

Primary Outcome Measure

Duration of invasive mechanical ventilation (time from randomisation to first successful unassisted breathing or death).

Secondary Outcome Measures

All-cause mortality at 2 and 6 months
Time to first extubation
Reintubation
Use of non-invasive ventilation following extubation
CCU and hospital length of stay
Serious adverse events up to hospital discharge
Health related quality of life (EQ-5D-5L) at 2 and 6 months after randomisation
Acute health care use at 2 and 6 months after randomisation

Eligibility Criteria

Patients are eligible to be included in the trial if they meet all the inclusion criteria and none of the absolute exclusion criteria. If a patient meets one of the temporary exclusion criteria, they can be re-screened within the 60 hour timeframe. If this resolves, the patient can be recruited into RELEASE:

Inclusion Criteria

Adult (age >18 years)
Receiving invasive mechanical ventilation
Moderate to severe AHRF (PaO2/FiO2<20kPa with PEEP ≥5 cmH2O assessed at time of screening (or as documented in the medical record in the preceding 2 hours) for trial inclusion.
Expected to require invasive mechanical ventilation for >48 hours

Exclusion Criteria

Absolute Exclusions	Temporary Exclusions
Receiving IMV ≥ 60 hours at time of screening as will be unable to deliver early APRV	Refractory shock (systolic blood pressure < 90 mmHg, despite fluid administration and vasoactive drugs)
Primary reason for invasive mechanical ventilation is one of the following: Asthma Severe COPD Pulmonary embolism (massive or sub-massive) Existing neuromuscular disease such as Motor Neurone Disease, Guillain Barré, or Myasthenia Gravis.	Severe hypercapnic respiratory acidosis (pH <7.20 on the arterial blood gas assessed for trial inclusion)
Likely death or treatment withdrawal in next 24 hours	Ongoing air leak (e.g. unresolved pneumothorax)
Home ventilation or home oxygen therapy prior to admission	Traumatic brain injury with uncontrolled intracranial hypertension