Kim KTMorton SHowe SChiew YSDesaive TBenyo BSzlavecz AMoeller KShaw, GeoffKnopp, JenniferDocherty, PaulPretty, ChristopherChase, Geoff2021-06-152021-06-152020Kim KT, Morton S, Howe S, Chiew YS, Knopp JL, Docherty P, Pretty C, Desaive T, Benyo B, Szlavecz A, Moeller K, Shaw GM, Chase JG (2020). Model-based PEEP titration versus standard practice in mechanical ventilation: A randomised controlled trial. Trials. 21(1). 130-.1745-6215https://hdl.handle.net/10092/102041Background: Positive end-expiratory pressure (PEEP) at minimum respiratory elastance during mechanical ventilation (MV) in patients with acute respiratory distress syndrome (ARDS) may improve patient care and outcome. The Clinical utilisation of respiratory elastance (CURE) trial is a two-arm, randomised controlled trial (RCT) investigating the performance of PEEP selected at an objective, model-based minimal respiratory system elastance in patients with ARDS. Methods and design: The CURE RCT compares two groups of patients requiring invasive MV with a partial pressure of arterial oxygen/fraction of inspired oxygen (PaO2/FiO2) ratio ≤ 200; one criterion of the Berlin consensus definition of moderate (≤ 200) or severe (≤ 100) ARDS. All patients are ventilated using pressure controlled (bi-level) ventilation with tidal volume = 6-8 ml/kg. Patients randomised to the control group will have PEEP selected per standard practice (SPV). Patients randomised to the intervention will have PEEP selected based on a minimal elastance using a model-based computerised method. The CURE RCT is a single-centre trial in the intensive care unit (ICU) of Christchurch hospital, New Zealand, with a target sample size of 320 patients over a maximum of 3 years. The primary outcome is the area under the curve (AUC) ratio of arterial blood oxygenation to the fraction of inspired oxygen over time. Secondary outcomes include length of time of MV, ventilator-free days (VFD) up to 28 days, ICU and hospital length of stay, AUC of oxygen saturation (SpO )/FiO during MV, number of desaturation events (SpO < 88%), changes in respiratory mechanics and chest x-ray index scores, rescue therapies (prone positioning, nitric oxide use, extracorporeal membrane oxygenation) and hospital and 90-day mortality. Discussion: The CURE RCT is the first trial comparing significant clinical outcomes in patients with ARDS in whom PEEP is selected at minimum elastance using an objective model-based method able to quantify and consider both inter-patient and intra-patient variability. CURE aims to demonstrate the hypothesized benefit of patient-specific PEEP and attest to the significance of real-time monitoring and decision-support for MV in the critical care environment. Trial registration: Australian New Zealand Clinical Trial Registry, ACTRN12614001069640. Registered on 22 September 2014. (https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=366838&isReview=true) The CURE RCT clinical protocol and data usage has been granted by the New Zealand South Regional Ethics Committee (Reference number: 14/STH/132). 2 2 2enAll rights reserved unless otherwise statedRespiratory SystemHumansRespiratory Distress Syndrome, AdultOxygenBreath TestsRespiration, ArtificialPositive-Pressure RespirationOxygen ConsumptionComputer-Aided DesignMiddle AgedFemaleMaleRandomized Controlled Trials as TopicClinical Trials, Phase II as TopicVentilator-Induced Lung InjuryOutcome Assessment, Health CareARDSmechanical ventilationpulmonary mechanicsRCTPEEP titrationJournal Article2021-04-191102 Cardiorespiratory Medicine and Haematology1103 Clinical SciencesFields of Research::32 - Biomedical and clinical sciences::3202 - Clinical sciences::320212 - Intensive careFields of Research::32 - Biomedical and clinical sciences::3201 - Cardiovascular medicine and haematology::320103 - Respiratory diseasesFields of Research::40 - Engineering::4003 - Biomedical engineering::400306 - Computational physiologyhttp://doi.org/10.1186/s13063-019-4035-7