Platform of Randomized Adaptive Clinical Trials in Critical Illness
Status:
Recruiting
Trial end date:
2024-12-31
Target enrollment:
Participant gender:
Summary
PRACTICAL:
PRACTICAL is a randomized multifactorial adaptive platform trial for acute hypoxemic
respiratory failure (AHRF). This platform trial will evaluate novel interventions for
patients with AHRF across a range of severity states (i.e., not intubated, intubated with
lower or higher respiratory system elastance, requiring extracorporeal life support) and
across a range of investigational phases (i.e., preliminary mechanistic trials, full-scale
clinical trials).
ULTIMATE domain (currently enrolling):
The ULTIMATE pilot trial is a multi-center, randomized, open-label trial, embedded as a
domain within the PRACTICAL platform trial. 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.
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:
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).