Platform of Randomized Adaptive Clinical Trials in Critical Illness

简要总结

详细描述

EXPAND-ECLS domain: The EXPAND-ECLS pilot trial is a multi-center, randomized, open-label, feasibility trial, embedded as a domain within the PRACTICAL platform trial. The ULTIMATE arm of this domain will evaluate the effect of ultra-low intensity ventilation facilitated by CO2 removal through VV-ECMO versus best current conventional ventilation on all-cause hospital mortality among patients with early moderate-severe AHRF with high respiratory system elastance receiving potentially injurious mechanical ventilation. The PROACTIVE arm of this domain will evaluate the effect of ECMO-facilitated strategy of earlier awakening, extubation, and rehabilitation versus best current conventional ventilation on all-cause hospital mortality among patients with early moderate-severe AHRF with high respiratory system elastance receiving potentially injurious mechanical ventilation. Invasive Mechanical Ventilation (IMV) Strategies domain: The IMV Strategies domain will evaluate multiple novel invasive ventilation strategies in comparison to conventional lung-protective ventilation in patients with acute hypoxemic respiratory failure (AHRF). Multiple approaches to mechanical ventilation are used, and the optimal approach is unknown. An efficient strategy to identify the best strategy is to compare multiple potential approaches simultaneously to determine more rapidly (a) which interventions are least effective (and should be dropped), and (b) which interventions result in the best outcomes for patients. In the current domain design, we will compare the current recommended ventilation strategy to two new approaches: a strategy that targets lung-inflating (driving) pressure instead of lung-inflating (tidal) volume, and a strategy that aims to maintain an optimal level of breathing effort to prevent diaphragm atrophy and injury while maintaining safe lung-inflating pressures. CORT-E2 domain: The Corticosteroid Early and Extended (CORT-E2) Trial is a phase III, multicentre Bayesian randomized controlled trial (RCT), which includes two cohorts within the domain; one examining the role of early corticosteroids as compared to not extending in persisting AHRF due to COVID or non-COVID (Extended Cohort). ESCAPE domain: Evaluating Subphenotypes in Immunocompromized Patients with ARF (ESCAPE) Domain is a prospective, multicentre observational cohort study, to identify subphenotypes across immunocompromised patients with acute hypoxemic respiratory failure (AHRF) using clinical characteristics and biomarkers. This study will prospectively collect biomarkers at the onset of AHRF which will allow us to characterize the underlying pathophysiology of AHRF with better precision. FLUDRO domain: The Fludrocortisone in Acute Hypoxemic Respiratory Failure with Airspace Disease (FLUDRO-1) domain is a phase II I trial. The trial aims to provide direct clinical evidence to resolve a critical long-standing question regarding the use of steroids in the treatment of AHRF with airspace disease. FAST-3 domain: The Nebulized Furosemide for the Treatment of Pulmonary Inflammation in Patients with Respiratory Failure Secondary to Pulmonary Infection domain is a phase III trial. It aims to use nebulized furosemide as supportive therapy to improve Advanced Respiratory Support (ARS) free days up to day 28 in critically ill patients with AHRF. IMV-ECLS domain: The Invasive Mechanical Ventilation Strategies in Venovenous-Extracorporeal Life Support (PRESSURE; Positive Pressure to Maintain Lung Recruitment during Extracorporeal Life Support for Acute Hypoxemic Respiratory failure) is a pilot and feasibility trial. It aims to identify which positive end-expiratory pressure (PEEP) strategies improve lung function in patients with AHRF supported by ECLS. IMPROV domain: The Inspiratory Muscle Training in Patients Receiving Ongoing Mechanical Ventilation is a pilot and feasibility RCT. It is designed to establish the feasibility of a definitive RCT of inspiratory muscle training to accelerate recovery from AHRF.

主要结局

次要结局

• To assess adherence to our explicit mechanical ventilation protocols.(48 hours)
• To measure and understand the reasons for crossovers in each group(2 years)
• Duration of mechanical ventilation during index ICU admission(Until ICU discharge, typically within 28 days)
• Mortality at other endpoints(ICU discharge, hospital discharge, day 30, 180 days for CORT-E2, IMV, IMV-ECLS, and EXPAND-ECLS domains. For ESCAPE, Hospital mortality at 60 days and at 6-months. For FAST-3, all-cause mortality at 60 days post enrollment. For IMPROV at day 90.)
• Vital status(Day 90 and at 6 months)
• Duration of ICU admission(Until ICU discharge, typically within 28 days)
• Hospital length of stay(Until hospital discharge, assessed up to 4 weeks)
• ICU and hospital free days(For FAST-3: ICU discharge, hospital discharge, Day 28. For IMPROV: Day 90.)
• Discharge disposition.(Until hospital discharge, assessed up to 4 weeks)
• Days alive and at home to day 90(Day 90)
• Need for ICU readmission prior to hospital discharge(Until hospital discharge, assessed up to 4 weeks)
• Duration of NIV(Until ICU discharge, typically within 28 days)
• Duration of supplemental oxygen use(Until ICU discharge, typically within 28 days)
• Need for ECLS(Until ICU discharge, typically within 28 days)
• Duration of ECLS, only for patients who require ECLS(Until ICU discharge, typically within 28 days)
• Ventilator-free days until day 30 for CORT-E2, and until day 28 for FAST-3, FLUDRO-1 and ULTIMATE (an ordinal scale composed of survival to hospital discharge and days alive and free of ventilation where death in the hospital is assigned a score of -1).(Until day 30 for CORT-E2, and until day 28 for FAST-3, FLUDRO-1 and ULTIMATE)
• EQ-5-D at day 180(For CORT-E2, FAST-3, IMV, and IMV-ECLS domains: Day 180; For IMPROV domain: Day 90 and Day 180.)
• Montreal Cognitive Assessment (MoCA) At day 180(Day 180)
• Complications from corticosteroids.(Until hospital discharge, assessed up to 4 weeks)
• Reintubation during index ICU admission(Until ICU discharge, typically within 28 days)
• Number of reintubations up to tracheostomy during index hospitalization(Until hospital discharge)
• Tracheostomy during index ICU admission(Until ICU discharge, typically within 28 days)
• Re-cannulation to ECLS during index ICU admission(Until ICU discharge, typically within 28 days)
• Sequential Organ Failure Assessment (SOFA) score(Daily, for duration of intervention)
• Respiratory mechanics and gas exchange - Driving pressure.(Daily, for duration of intervention)
• Respiratory mechanics and gas exchange - Pocc.(Daily, for duration of intervention)
• Respiratory mechanics and gas exchange - P0.1(Daily, for duration of intervention)
• Respiratory mechanics and gas exchange - plateau airway pressure(Daily, for duration of intervention)
• Respiratory mechanics and gas exchange - P/F ratio(Daily, for duration of intervention)
• Respiratory mechanics and gas exchange - ventilatory ratio(Daily, for duration of intervention)
• Diaphragm thickness(Daily, for duration of intervention)
• Maximal diaphragm thickening fraction(During first SBT)
• Survival status at disconnection from mechanical ventilation (dead or alive)(Until day 28)
• Organ failure-free days(Until day 28)
• Serious adverse events (SAEs)(Throughout the trial)
• Modified Lung Injury Score (mLIS)(Until day 10)
• Number of days from first SBT to disconnection from mechanical ventilation(Until ICU discharge)
• Barotrauma during hospital admission(Until 45 days or hospital discharge)
• Cardiac arrest during hospital admission(Until 45 days or hospital discharge)
• 30 second sit to stand test at ICU discharge and hospital discharge(Until ICU discharge, typically within 28 days)
• Modified Medical Research Council (mMRC) Dyspnea Scale(At ICU discharge, Day 90, Day 180)
• Physical function (Activity Measure for Post-Acute Care)(At ICU discharge, Day 90, Day 180)