Presneill Jeffrey, Little Lorraine, Nichol Alistair, French Craig, Cooper D James, Haddad Samir, Duranteau Jacques, Huet Olivier, Skrifvars Markus, Arabi Yaseen, Bellomo Rinaldo
Australian and New Zealand Intensive Care Research Centre, Monash University School of Public Health and Preventive Medicine, 99 Commercial Road, Melbourne, 3004, Australia.
Department of Intensive Care, Mater Health Services, Raymond Terrace, South Brisbane, 4101, Australia.
Trials. 2014 Dec 20;15:501. doi: 10.1186/1745-6215-15-501.
The Erythropoietin in Traumatic Brain Injury (EPO-TBI) trial aims to determine whether the administration of erythropoietin to patients with moderate or severe traumatic brain injury improves patient-centred outcomes.
EPO-TBI is a multicentre, blinded, randomised, parallel groups, placebo-controlled, phase III superiority trial of erythropoietin in ICU patients with traumatic brain injury conducted in Australia and New Zealand, Saudi Arabia and Europe; 606 critically ill patients aged 15 to 65 years with moderate or severe acute traumatic brain injury will be enrolled. Trial patients will receive either 40,000 IU erythropoietin or placebo by subcutaneous injection administered weekly for up to three doses during their ICU admission. The primary outcome measure is the proportion of unfavourable neurological outcomes, comprising death or severe disability, observed at 6 months following randomisation utilizing the Extended Glasgow Outcome Scale. Secondary outcomes, also assessed at 6 months following randomisation, include the probability of an equal or greater Extended Glasgow Outcome Scale level, mortality, the proportions of patients with proximal deep venous thrombosis or with composite thrombotic vascular events, as well as assessment of quality of life and cost-effectiveness. The planned sample size will allow 90% power to detect a reduction from 50% to 36% in unfavourable neurological outcomes at a two-sided alpha of 0.05.
A detailed analysis plan has been developed for EPO-TBI that is consistent with international guidelines. This plan specifies the statistical models for evaluation of primary and secondary outcomes, as well as defining covariates for adjusted analyses. Application of this statistical analysis plan to the forthcoming EPO-TBI trial will facilitate unbiased analyses of these important clinical data.
Australian New Zealand Clinical Trials Registry: ACTRN12609000827235 (22 September 2009). ClinicalTrials.gov: NCT00987454 (29 September 2009). European Drug Regulatory Authorities Clinical Trials: 2011-005235-22 (18 January 2012).
创伤性脑损伤促红细胞生成素（EPO-TBI）试验旨在确定对中重度创伤性脑损伤患者使用促红细胞生成素是否能改善以患者为中心的预后。
EPO-TBI是一项在澳大利亚和新西兰、沙特阿拉伯及欧洲开展的多中心、双盲、随机、平行组、安慰剂对照的促红细胞生成素III期优效性试验，针对入住重症监护病房（ICU）的创伤性脑损伤患者；将招募606名年龄在15至65岁之间的中重度急性创伤性脑损伤重症患者。试验患者将在入住ICU期间每周皮下注射一次40000国际单位促红细胞生成素或安慰剂，最多注射三剂。主要结局指标是随机分组后6个月时观察到的不良神经学结局的比例，采用扩展格拉斯哥预后量表评估，包括死亡或严重残疾。次要结局指标也在随机分组后6个月进行评估，包括扩展格拉斯哥预后量表水平相等或更高的概率、死亡率、近端深静脉血栓形成或复合血栓性血管事件患者的比例，以及生活质量和成本效益评估。计划样本量将使在双侧α为0.05时，有90%的把握度检测到不良神经学结局从50%降至36%。
已为EPO-TBI制定了一份与国际指南一致的详细分析计划。该计划规定了评估主要和次要结局的统计模型，以及定义用于调整分析的协变量。将此统计分析计划应用于即将开展的EPO-TBI试验将有助于对这些重要临床数据进行无偏倚分析。
澳大利亚新西兰临床试验注册中心：ACTRN12609000827235（2009年9月22日）。ClinicalTrials.gov：NCT00987454（2009年9月29日）。欧洲药品监管机构临床试验：2011-005235-22（2012年1月18日）。
