Acute hypoxemic respiratory failure (AHRF) is a common, life-threatening condition associated with substantial morbidity and mortality. Many acute and critical illnesses, including covid-19, can cause AHRF and leave patients vulnerable to lung and diaphragm injury associated with mechanical ventilation along with other nosocomial complications of critical care. While substantial progress has been made to reduce these risks and improve outcomes, many aspects of care for patients with AHRF remain untested and poorly defined. The PRACTICAL randomised controlled platform trial will enable phase II and III evaluation of a range of potential treatments to improve outcomes for patients with AHRF.
The primary objective of this adaptive platform trial is to test the efficacy of novel interventions for patients with AHRF on mechanistic surrogate endpoints and short-term and long-term patient-centred outcomes. The PRACTICAL trial will use a randomised, embedded, multifactorial adaptive platform (REMAP) design. This design is the basis of a perpetual trial to assess novel therapies for patients with AHRF efficiently and effectively. The trial is structured across independent domains, where patients are allocated to two or more interventional arms that will be compared against each other. Individuals may receive interventions from multiple domains. Domain-specific eligibility will be dependant on a patient’s state. States are a set of mutually exclusive clinical conditions, defined by a patient’s disease characteristics.
This trial design requires bespoke statistical design and analysis, which is being led by the IMPaCT lab. Inferences in this trial will be based on a Bayesian statistical model, which estimates the posterior distribution of the parameter of interest, based on the accumulating data in the trial and pre-specified prior distributions. All trial conclusions will be based on the Bayesian posterior probability that a given treatment results in the best patient outcomes, measured by the domain-specific primary endpoint, compared to the current set of treatments randomized in that domain for individuals in that state. Trial operating characteristics will be assessed using comprehensive simulation methods. Through these statistical and clinical innovations, the PRACTICAL trial will improve outcomes of patients with AHRF efficiently and dynamically.