Abstract

METHODS: Erythropoietin in Traumatic Brain Injury (EPO-TBI) was a double-blind, placebo-controlled trial undertaken in 29 centres (all university-affiliated teaching hospitals) in seven countries (Australia, New Zealand, France, Germany, Finland, Ireland, and Saudi Arabia). Within 24 h of brain injury, 606 patients were randomly assigned by a concealed web-based computer-generated randomisation schedule to erythropoietin (40,000 units subcutaneously) or placebo (0?9 sodium chloride subcutaneously) once per week for a maximum of three doses. Randomisation was stratified by severity of traumatic brain injury (moderate vs severe) and participating site. With the exception of designated site pharmacists, the site dosing nurses at all sites, and the pharmacists at the central pharmacy in France, all study personnel, patients, and patients relatives were masked to treatment assignment. The primary outcome, assessed at 6 months by modified intention-to-treat analysis, was improvement in the patients neurological status, summarised as a reduction in the proportion of patients with an Extended Glasgow Outcome Scale (GOS-E) of 1-4 (death, vegetative state, and severe disability). Two equally spaced preplanned interim analyses were done (after 202 and 404 participants were enrolled). This study is registered with ClinicalTrials.gov, number NCT00987454. FINDINGS: Between May 3, 2010, and Nov 1, 2014, 606 patients were enrolled and randomly assigned to erythropoietin (n=308) or placebo (n=298). Ten of these patients (six in the erythropoietin group and four in the placebo group) were lost to follow up at 6 months; therefore, data for the primary outcome analysis was available for 596 patients (302 in the erythropoietin group and 294 in the placebo group). Compared with placebo, erythropoietin did not reduce the proportion of patients with a GOS-E level of 1-4 (134 [44 of 302 patients in the erythropoietin group vs 132 [45 of 294 in the placebo group; relative risk [RR] 0?99 [95 CI 0?83-1?18], p=0?90). In terms of safety, erythropoietin did not significantly affect 6-month mortality versus placebo (32 [11 of 305 patients had died at 6 months in the erythropoietin group vs 46 [16 of 297 [16 in the placebo group; RR 0?68 [95 CI 0?44-1?03], p=0?07) or increase the occurrence of deep venous thrombosis of the lower limbs (48 [16 of 305 vs 54 [18 of 298; RR 0?87 [95 CI 0?61-1?24], p=0?44). INTERPRETATION: Following moderate or severe traumatic brain injury, erythropoietin did not reduce the number of patients with severe neurological dysfunction (GOS-E level 1-4) or increase the incidence of deep venous thrombosis of the lower limbs. The effect of erythropoietin on mortality remains uncertain. FUNDING: The National Health and Medical Research Council and the Transport Accident Commission. BACKGROUND: Erythropoietin might have neurocytoprotective effects. In this trial, we studied its effect on neurological recovery, mortality, and venous thrombotic events in patients with traumatic brain injury.
Original languageEnglish
Pages (from-to)2499 - 2506
Number of pages8
JournalThe Lancet
Volume386
Issue number10012
DOIs
Publication statusPublished - 2015

Cite this

@article{80d64a54102b45bb82faaafe41b53020,
title = "Erythropoietin in traumatic brain injury (EPO-TBI): a double-blind randomised controlled trial",
abstract = "METHODS: Erythropoietin in Traumatic Brain Injury (EPO-TBI) was a double-blind, placebo-controlled trial undertaken in 29 centres (all university-affiliated teaching hospitals) in seven countries (Australia, New Zealand, France, Germany, Finland, Ireland, and Saudi Arabia). Within 24 h of brain injury, 606 patients were randomly assigned by a concealed web-based computer-generated randomisation schedule to erythropoietin (40,000 units subcutaneously) or placebo (0?9 sodium chloride subcutaneously) once per week for a maximum of three doses. Randomisation was stratified by severity of traumatic brain injury (moderate vs severe) and participating site. With the exception of designated site pharmacists, the site dosing nurses at all sites, and the pharmacists at the central pharmacy in France, all study personnel, patients, and patients relatives were masked to treatment assignment. The primary outcome, assessed at 6 months by modified intention-to-treat analysis, was improvement in the patients neurological status, summarised as a reduction in the proportion of patients with an Extended Glasgow Outcome Scale (GOS-E) of 1-4 (death, vegetative state, and severe disability). Two equally spaced preplanned interim analyses were done (after 202 and 404 participants were enrolled). This study is registered with ClinicalTrials.gov, number NCT00987454. FINDINGS: Between May 3, 2010, and Nov 1, 2014, 606 patients were enrolled and randomly assigned to erythropoietin (n=308) or placebo (n=298). Ten of these patients (six in the erythropoietin group and four in the placebo group) were lost to follow up at 6 months; therefore, data for the primary outcome analysis was available for 596 patients (302 in the erythropoietin group and 294 in the placebo group). Compared with placebo, erythropoietin did not reduce the proportion of patients with a GOS-E level of 1-4 (134 [44 of 302 patients in the erythropoietin group vs 132 [45 of 294 in the placebo group; relative risk [RR] 0?99 [95 CI 0?83-1?18], p=0?90). In terms of safety, erythropoietin did not significantly affect 6-month mortality versus placebo (32 [11 of 305 patients had died at 6 months in the erythropoietin group vs 46 [16 of 297 [16 in the placebo group; RR 0?68 [95 CI 0?44-1?03], p=0?07) or increase the occurrence of deep venous thrombosis of the lower limbs (48 [16 of 305 vs 54 [18 of 298; RR 0?87 [95 CI 0?61-1?24], p=0?44). INTERPRETATION: Following moderate or severe traumatic brain injury, erythropoietin did not reduce the number of patients with severe neurological dysfunction (GOS-E level 1-4) or increase the incidence of deep venous thrombosis of the lower limbs. The effect of erythropoietin on mortality remains uncertain. FUNDING: The National Health and Medical Research Council and the Transport Accident Commission. BACKGROUND: Erythropoietin might have neurocytoprotective effects. In this trial, we studied its effect on neurological recovery, mortality, and venous thrombotic events in patients with traumatic brain injury.",
author = "Nichol, {Alistair Dualta} and French, {Craig J} and Little, {Lorraine Mary} and Samir Haddad and Presneill, {Jeffrey J} and Arabi, {Yaseen M} and Bailey, {Michael John} and Cooper, {David James} and Jacques Duranteau and Olivier Huet and Anne Mak and Colin McArthur and Pettila, {Ville Yrjo Olavi} and Markus Skrifvars and Shirley Vallance and Varma, {Dinesh Kumar} and Judy Wills and Rinaldo Bellomo",
year = "2015",
doi = "10.1016/S0140-6736(15)00386-4",
language = "English",
volume = "386",
pages = "2499 -- 2506",
journal = "The Lancet",
issn = "0140-6736",
publisher = "Elsevier",
number = "10012",

}

TY - JOUR

T1 - Erythropoietin in traumatic brain injury (EPO-TBI): a double-blind randomised controlled trial

AU - Nichol, Alistair Dualta

AU - French, Craig J

AU - Little, Lorraine Mary

AU - Haddad, Samir

AU - Presneill, Jeffrey J

AU - Arabi, Yaseen M

AU - Bailey, Michael John

AU - Cooper, David James

AU - Duranteau, Jacques

AU - Huet, Olivier

AU - Mak, Anne

AU - McArthur, Colin

AU - Pettila, Ville Yrjo Olavi

AU - Skrifvars, Markus

AU - Vallance, Shirley

AU - Varma, Dinesh Kumar

AU - Wills, Judy

AU - Bellomo, Rinaldo

PY - 2015

Y1 - 2015

N2 - METHODS: Erythropoietin in Traumatic Brain Injury (EPO-TBI) was a double-blind, placebo-controlled trial undertaken in 29 centres (all university-affiliated teaching hospitals) in seven countries (Australia, New Zealand, France, Germany, Finland, Ireland, and Saudi Arabia). Within 24 h of brain injury, 606 patients were randomly assigned by a concealed web-based computer-generated randomisation schedule to erythropoietin (40,000 units subcutaneously) or placebo (0?9 sodium chloride subcutaneously) once per week for a maximum of three doses. Randomisation was stratified by severity of traumatic brain injury (moderate vs severe) and participating site. With the exception of designated site pharmacists, the site dosing nurses at all sites, and the pharmacists at the central pharmacy in France, all study personnel, patients, and patients relatives were masked to treatment assignment. The primary outcome, assessed at 6 months by modified intention-to-treat analysis, was improvement in the patients neurological status, summarised as a reduction in the proportion of patients with an Extended Glasgow Outcome Scale (GOS-E) of 1-4 (death, vegetative state, and severe disability). Two equally spaced preplanned interim analyses were done (after 202 and 404 participants were enrolled). This study is registered with ClinicalTrials.gov, number NCT00987454. FINDINGS: Between May 3, 2010, and Nov 1, 2014, 606 patients were enrolled and randomly assigned to erythropoietin (n=308) or placebo (n=298). Ten of these patients (six in the erythropoietin group and four in the placebo group) were lost to follow up at 6 months; therefore, data for the primary outcome analysis was available for 596 patients (302 in the erythropoietin group and 294 in the placebo group). Compared with placebo, erythropoietin did not reduce the proportion of patients with a GOS-E level of 1-4 (134 [44 of 302 patients in the erythropoietin group vs 132 [45 of 294 in the placebo group; relative risk [RR] 0?99 [95 CI 0?83-1?18], p=0?90). In terms of safety, erythropoietin did not significantly affect 6-month mortality versus placebo (32 [11 of 305 patients had died at 6 months in the erythropoietin group vs 46 [16 of 297 [16 in the placebo group; RR 0?68 [95 CI 0?44-1?03], p=0?07) or increase the occurrence of deep venous thrombosis of the lower limbs (48 [16 of 305 vs 54 [18 of 298; RR 0?87 [95 CI 0?61-1?24], p=0?44). INTERPRETATION: Following moderate or severe traumatic brain injury, erythropoietin did not reduce the number of patients with severe neurological dysfunction (GOS-E level 1-4) or increase the incidence of deep venous thrombosis of the lower limbs. The effect of erythropoietin on mortality remains uncertain. FUNDING: The National Health and Medical Research Council and the Transport Accident Commission. BACKGROUND: Erythropoietin might have neurocytoprotective effects. In this trial, we studied its effect on neurological recovery, mortality, and venous thrombotic events in patients with traumatic brain injury.

AB - METHODS: Erythropoietin in Traumatic Brain Injury (EPO-TBI) was a double-blind, placebo-controlled trial undertaken in 29 centres (all university-affiliated teaching hospitals) in seven countries (Australia, New Zealand, France, Germany, Finland, Ireland, and Saudi Arabia). Within 24 h of brain injury, 606 patients were randomly assigned by a concealed web-based computer-generated randomisation schedule to erythropoietin (40,000 units subcutaneously) or placebo (0?9 sodium chloride subcutaneously) once per week for a maximum of three doses. Randomisation was stratified by severity of traumatic brain injury (moderate vs severe) and participating site. With the exception of designated site pharmacists, the site dosing nurses at all sites, and the pharmacists at the central pharmacy in France, all study personnel, patients, and patients relatives were masked to treatment assignment. The primary outcome, assessed at 6 months by modified intention-to-treat analysis, was improvement in the patients neurological status, summarised as a reduction in the proportion of patients with an Extended Glasgow Outcome Scale (GOS-E) of 1-4 (death, vegetative state, and severe disability). Two equally spaced preplanned interim analyses were done (after 202 and 404 participants were enrolled). This study is registered with ClinicalTrials.gov, number NCT00987454. FINDINGS: Between May 3, 2010, and Nov 1, 2014, 606 patients were enrolled and randomly assigned to erythropoietin (n=308) or placebo (n=298). Ten of these patients (six in the erythropoietin group and four in the placebo group) were lost to follow up at 6 months; therefore, data for the primary outcome analysis was available for 596 patients (302 in the erythropoietin group and 294 in the placebo group). Compared with placebo, erythropoietin did not reduce the proportion of patients with a GOS-E level of 1-4 (134 [44 of 302 patients in the erythropoietin group vs 132 [45 of 294 in the placebo group; relative risk [RR] 0?99 [95 CI 0?83-1?18], p=0?90). In terms of safety, erythropoietin did not significantly affect 6-month mortality versus placebo (32 [11 of 305 patients had died at 6 months in the erythropoietin group vs 46 [16 of 297 [16 in the placebo group; RR 0?68 [95 CI 0?44-1?03], p=0?07) or increase the occurrence of deep venous thrombosis of the lower limbs (48 [16 of 305 vs 54 [18 of 298; RR 0?87 [95 CI 0?61-1?24], p=0?44). INTERPRETATION: Following moderate or severe traumatic brain injury, erythropoietin did not reduce the number of patients with severe neurological dysfunction (GOS-E level 1-4) or increase the incidence of deep venous thrombosis of the lower limbs. The effect of erythropoietin on mortality remains uncertain. FUNDING: The National Health and Medical Research Council and the Transport Accident Commission. BACKGROUND: Erythropoietin might have neurocytoprotective effects. In this trial, we studied its effect on neurological recovery, mortality, and venous thrombotic events in patients with traumatic brain injury.

UR - http://www.thelancet.com/pdfs/journals/lancet/PIIS0140-6736(15)00386-4.pdf

U2 - 10.1016/S0140-6736(15)00386-4

DO - 10.1016/S0140-6736(15)00386-4

M3 - Article

VL - 386

SP - 2499

EP - 2506

JO - The Lancet

JF - The Lancet

SN - 0140-6736

IS - 10012

ER -