Statistical analysis plan for the Erythropoietin in Traumatic Brain Injury trial: A randomised controlled trial of erythropoietin versus placebo in moderate and severe traumatic brain injury

被引：15
作者：
Presneill J. [1 ,2 ]
Little L. [1 ]
Nichol A. [1 ,3 ,4 ,5 ]
French C. [6 ,7 ]
Cooper D.J. [1 ,5 ]
Haddad S. [1 ,8 ]
Duranteau J. [1 ,9 ]
Huet O. [10 ]
Skrifvars M. [11 ]
Arabi Y. [1 ,12 ]
Bellomo R. [1 ,7 ,13 ]
the ANZICS Clinical Trials Group
on behalf of the EPO-TBI Investigators
机构：
[1] Monash University School of Public Health and Preventive Medicine, Australian and New Zealand Intensive Care Research Centre, 99 Commercial Road, Melbourne
[2] Department of Intensive Care, Mater Health Services, Raymond Terrace, South Brisbane
[3] St Vincent's University Hospital, Department of Anaesthesia and Intensive Care Medicine, Elm Park
[4] University College, School of Medicine and Medical Sciences, Elm Park
[5] The Alfred, Department of Intensive Care Medicine, Commercial Road, Melbourne
[6] Western Health, Department of Intensive Care, Gordon Street, Footscray
[7] The University of Melbourne, Grattan Street, Parkville
[8] King Abdulaziz Medical City, Intensive Care Department, PO Box 22490, Riyadh
[9] Hôpital de Bicêtre, Service d'Anesthésie-Réanimation, Hôpitaux universitaires Paris Sud, Assistance Publique des Hôpitaux de Paris, 78, rue du Général Leclerc, Paris, Le Kremlin Bicêtre
[10] CHRU La Cavale Blanche Université de Bretagne Ouest, Department of Anesthesiology and Intensive Care Medicine, Brest, Cedex
[11] Helsinki University Hospital, Department of Anaesthesiology and Intensive Care Medicine, P.O. Box 266, Helsinki
[12] College of Medicine King Saud Bin Abdulaziz University for Health Sciences, King Abdullah International Medical Research Center, Intensive Care Department, PO Box 22490, Riyadh
[13] Austin Health, Department of Intensive Care, Studley Road, Heidelberg
来源：
Trials | / 15卷 / 1期
基金：
英国医学研究理事会;
关键词：
Critical care; Erythropoietin; Outcome; Randomised controlled trials; Traumatic brain injury;
D O I：
10.1186/1745-6215-15-501
中图分类号：
学科分类号：
摘要：
Background: 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. Methods: 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. Discussion: 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. Trial registration: 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). © 2014 Presneill et al.
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