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PROTO
OCOLSU
UMMARY
Y

FULLTITLEOFFSTUDY:

Tranexam
micacidforthetreatmen
ntofsignificaanttraumaticcbraininjuryy:
aninternationalrandomised,dou
ubleblindplaacebocontro
olledtrial

SHORTTITLE:

Clinicalraandomisationofanantifibrinolyticin
nsignificanth
headinjury

TRIALACRON
NYM:

CRASH3

PROTOCOLNUMBER:

ISRCTN15
5088122

EUDRACTNUMBER
U
:

2011003
366914

CLINICALTRIALS.GOVID:

NCT01
1402882

BACKGROUND
D:Worldwid
de,over10m
millionpeopllearekilledo
orhospitalisedbecauseoftraumaticcbraininjuryy
(TBI)eachyyear.About9
90%ofdeath
hsfromTBIo
occurinlowandmiddleincomecoun
ntries.TBIm
mostlyaffectss
youngadulttsandmanyyexperience longlasting orpermane
entdisability.Thesocialaandeconom
micburdenoff
TBI is considerable. Traanexamic aciid (TXA) is co
ommonly givven to surgical patients to reduce bleeding
b
and
d
orbloodtran
nsfusion.TXAhasbeen showntore
educe thenu
umberof paatientsreceivvingablood
d
the needfo
transfusion by about a third, reducces the volu
ume of blood
d transfused
d by about o
one unit, and
d halves thee
urther surgerry to contro
ol bleeding in
n elective su
urgical patients. The CRA
ASH2 trial showed
s
thatt
need for fu
administrattionofTXAssignificantly reducesdeaathsdueto bleeding(RR
R=0.85,95% CI0.760.9
96;p=0.008),,
and allcause mortalityy (RR=0.91, 95% CI 0.850.97; p=0
0.0035), with
h no increasse in vascular occlusivee
m
mised contro
olled trials of
o TXA in TB
BI showed a significant reduction in
n
events. A metaanalysi
s of random
haemorrhagge growth (RR=0.72; 95
5% CI 0.550
0.94) and mortality (RR==0.63; 95% CI 0.400.99
9) with TXA..
Althoughth
heresultsfro
omthesetriaalsareprom
mising,theesstimatesare impreciseandthereare
enodataon
n
theeffecto
ofTXAondisability.
AIM: TheCR
RASH3trial willprovideereliableevidenceaboutttheeffect oftranexam
micacidonm
mortalityand
d
disabilityinpatientswitthTBI.TheeffectofTXAontherisko
ofvascularocclusiveeven
ntsandseizu
ureswillalso
o
beassessed
d.
OUTCOME:
U
:Theprimaryoutccomeisdeatthinhospitalwithin28d
daysofinjuryy(causeofde
eathwillbe
PRIMARYOUTCOME
described).
SECONDARYO
OUTCOMES:
(a) Vasculaarocclusiveeevents(myoccardialinfarcction,pulmo
onaryembolism,clinicaleevidenceofdeepvein
thromb
bosis)
(b) Stroke
(c) InhospitaldisabilityyassessedussingtheDisaabilityRatinggScaleandPatientOrienttatedOutcome
(d) Seizuress
(e) Neurosurgicalintervvention
(f) Daysinintensivecaare
(g) Otheraadverseeven
nts

CRASH3Pro
otocolSummaryversion1.0
0dated1Octo
ober2011

Page1of2

TRIAL DESIGN:Apragmatic,randomised,doubleblind,placebocontrolledtrialamong10,000traumaticbrain
injurypatients
DIAGNOSISANDINCLUSION/EXCLUSIONCRITERIA:
Adultswithtraumaticbraininjurywho
arewithineighthoursofinjury
withanyintracranialbleedingonCTscanorwhohaveaGCSof12orless,and
havenosignificantextracranialbleeding(needingimmediatebloodtransfusion)
Thefundamentaleligibilitycriterionistheresponsiblecliniciansuncertaintyastowhetherornottouse
tranexamicacidinaparticularpatientwithtraumaticbraininjury.
TEST PRODUCT, REFERENCE THERAPY, DOSE AND MODE OF ADMINISTRATION: A loading dose of tranexamic acid (1
gram by intravenous injection) or placebo (sodium chloride 0.9%) will be given as soon as possible after
randomisation. A maintenance dose of tranexamic acid (1 gram by intravenous injection) or placebo
(sodiumchloride0.9%)willbegivenaftertheloadingdoseisfinished.
SETTING: ThistrialwillbecoordinatedfromtheLondonSchoolofHygiene&TropicalMedicine(Universityof
London)andconductedworldwideinhospitalsinlow,middleandhighincomecountries.
DURATION OF TREATMENT AND PARTICIPATION: The loading dose will be given as soon as possible after
randomisationandthemaintenancedosewillbegivenimmediatelyaftertheloadingdoseover8hours.
CRITERIAFOREVALUATION: Allpatientsrandomlyassignedtooneofthetreatmentswillbeanalysedtogether,
regardlessofwhetherornottheycompletedorreceivedthattreatment,onanintentiontotreatbasis.
CLINICALPHASE

PLANNEDTRIALSTART

01December2011

PLANNEDDATEOFLAST
PATIENTENROLMENT

31December2016

PLANNEDDATEOFLAST
OUTCOME

31January2017

CRASH3ProtocolSummaryversion1.0dated1October2011

Page2of2