Incept : The Intensive Care Platform Trial-Design and protocol

Abstract

BACKGROUND: Adult intensive care unit (ICU) patients receive many interventions, but few are supported by high-certainty evidence. Randomised clinical trials (RCTs) are essential for trustworthy comparisons of intervention effects, but conventional RCTs are costly, cumbersome, inflexible, and often turn out inconclusive. Adaptive platform trials may mitigate these issues and have higher probabilities of obtaining conclusive results faster and at lower costs per participant. METHODS: The Intensive Care Platform Trial (INCEPT) is an investigator-initiated, pragmatic, randomised, embedded, multifactorial, international, adaptive platform trial including adults acutely admitted to ICUs. INCEPT will assess comparable groups of interventions (primarily commonly used interventions with clinical uncertainty and practice variation) nested in domains. Interventions may be either open-label or masked. New domains will continuously be added to the platform. INCEPT assesses multiple core outcomes selected following substantial stakeholder involvement: mortality, days alive without life support/out of hospital/free of delirium, health-related quality of life, cognitive function, and safety outcomes. Each domain will use one of these core outcomes as the primary outcome. INCEPT primarily uses Bayesian statistical methods with neutral, minimally informative or sceptical priors, adjustment for important prognostic baseline variables, and calculation of absolute and relative differences in the intention-to-treat populations. Domains and intervention arms may be stopped for superiority/inferiority, practical equivalence, or futility according to pre-specified adaptation rules evaluated using statistical simulation or at pre-specified maximum sample sizes. Domains may use response-adaptive randomisation, meaning that more participants will be allocated to interventions with higher probabilities of being superior. CONCLUSIONS: INCEPT provides an efficient, pragmatic, and flexible platform for comparing the effects of many interventions used in adult ICU patients. The adaptive design enables the trial to use accumulating data to improve the treatment of future participants. INCEPT will provide high-certainty, conclusive evidence for many interventions, directly inform clinical practice, and thus improve patient-important outcomes.