Granholm Anders, Møller Morten Hylander, Kaas-Hansen Benjamin Skov, Jensen Aksel Karl Georg, Munch Marie Warrer, Kjær Maj-Brit Nørregaard, Andersen Lars Wiuff, Schjørring Olav Lilleholt, Rasmussen Bodil Steen, Meyhoff Tine Sylvest, Larsen Rikke Faebo, Thorsen-Meyer Hans-Christian, Collet Marie Oxenbøll, Meier Nick Frørup, Estrup Stine, Mathiesen Ole, Maagaard Mathias, Poulsen Lone Musaeus, Strøm Thomas, Christensen Steffen, Bruun Camilla Rahbek Lysholm, Keus Frederik, Rossing Peter, Granfeldt Asger, Brøchner Anne Craveiro, Itenov Theis Skovsgaard, Cronhjort Maria, Laake Jon Henrik, Hästbacka Johanna, Pfortmueller Carmen Andrea, Siegemund Martin, Sigurdsson Martin Ingi, Andersen Lars Peter Kloster, Placido Davide, Lange Theis, Perner Anders
Department of Intensive Care, Copenhagen University Hospital-Rigshospitalet, Copenhagen, Denmark.
Section of Biostatistics, Department of Public Health, University of Copenhagen, Copenhagen, Denmark.
Acta Anaesthesiol Scand. 2025 Apr;69(4):e70023. doi: 10.1111/aas.70023.
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.
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.
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.
成人重症监护病房（ICU）患者会接受多种干预措施，但很少有措施得到高确定性证据的支持。随机临床试验（RCT）对于可靠地比较干预效果至关重要，但传统的RCT成本高昂、操作繁琐、缺乏灵活性，而且往往没有定论。适应性平台试验可能会缓解这些问题，并且更有可能以更低的每位参与者成本更快地获得确定性结果。
重症监护平台试验（INCEPT）是一项由研究者发起的、务实的、随机的、嵌入式的、多因素的、国际性的适应性平台试验，纳入急性入住ICU的成人患者。INCEPT将评估嵌套在各个领域中的可比较干预组（主要是存在临床不确定性和实践差异的常用干预措施）。干预措施可以是开放标签或设盲的。新的领域将不断添加到该平台。INCEPT评估在大量利益相关者参与后选定的多个核心结局：死亡率、无生命支持存活天数/出院天数/无谵妄天数、健康相关生活质量、认知功能和安全性结局。每个领域将使用这些核心结局之一作为主要结局。INCEPT主要使用贝叶斯统计方法，采用中性、信息量最少或持怀疑态度的先验概率，对重要的预后基线变量进行调整，并计算意向性治疗人群中的绝对和相对差异。根据使用统计模拟评估的预先指定的适应性规则或在预先指定的最大样本量时，各领域和干预组可能会因优效性/劣效性、实际等效性或无效性而停止。各领域可能会使用反应自适应随机化，这意味着更多参与者将被分配到更有可能具有优效性的干预措施中。
INCEPT为比较成人ICU患者使用的多种干预措施的效果提供了一个高效、务实且灵活的平台。适应性设计使该试验能够利用不断积累的数据来改善对未来参与者的治疗。INCEPT将为多种干预措施提供高确定性、确凿的证据，直接为临床实践提供信息，从而改善对患者至关重要的结局。
