[ Print-friendly version ] Tranexamic acid for IntraCerebral Haemorrhage TICH-2 ISRCTN DOI ClinicalTrials.gov identifier !draCT n!mber "!

blic title Scientific title 2012-00410 -37 Tr#ne$#%i& #&id for Intr#Cere'r#l (#e%orr)#*e TIC(-2 Tr#ne$#%i& #&id for Intr#Cere'r#l (#e%orr)#*e TIC(-2+ # ,r#*%#ti& ,)#se III ,ros,e&tive do-'le 'lind r#ndo%ised ,l#&e'o &ontrolled tri#l TIC(-2 (T.+ 11"129"109/ 134!7 0)en so%eone )#s # stro1e &#-sed 'y 'leedin* into t)e 'r#in 2)#e%orr)#*i& stro1e3 ,er%#nent 'r#in d#%#*e &#n o&&-r #nd res-lt in lon* ter% dis#'ility. T)ere is #lso # &)#n&e t)#t t)e 'leedin* &#n in&re#se/ 4)i&) %#y &#-se 4orse dis#'ility or 'e life t)re#tenin*. .t ,resent t)ere is no effe&tive tre#t%ent #v#il#'le to red-&e t)e 'leedin* in t)e 'r#in #nd i%,rovin* t)e re&overy. Ne4 tre#t%ents #re 'ein* develo,ed to tre#t stro1e/ '-t it &#n 'e very )#rd to test 4)et)er t)ey 4or1 in t)e first fe4 )o-rs 'e&#-se often ,#tients t#1e lon*er t)#n t)is to *et to )os,it#l #nd )#ve investi*#tions s-&) #s 'r#in s&#nnin*. .lso so%e tre#t%ents #re not s-it#'le for #ll ,#tients. In t)is tri#l/ t)e #i% is to test 4)et)er it is ,ossi'le to *ive tr#ne$#%i& #&id to ,#tients in t)e first fe4 )o-rs #fter # )#e%orr)#*i& stro1e #nd find o-t if it red-&es t)e &)#n&es of dyin* #nd 'ein* left 4it) dis#'ility. Tr#ne$#%i& #&id en&o-r#*es 'lood to &lot to sto, 'leedin*. Contin-ed or in&re#sed 'leedin* into t)e 'r#in 2so &#lled )#e%#to%# e$,#nsion3 is not -n&o%%on in t)e first )o-rs #nd d#ys follo4in* # )#e%orr)#*i& stro1e #nd in&re#ses t)e ris1 of t)e ,#tient not re&overin* f-lly #nd 'ein* left 4it) so%e dis#'ility/ or dyin*. Sto,,in* t)e 'leedin* in t)e first )o-rs #fter stro1e 4it) %edi&#tions %i*)t )el, ,#tients to re&over 'etter #nd red-&e t)e n-%'er of ,#tients 4)o die. T)e d#t# 4ill )el, do&tors de&ide 4)et)er 'lood t)i&1enin* tre#t%ents li1e tr#ne$#%i& #&id &#n 'e -sed in ,#tients 4it) #&-te )#e%orr)#*i& stro1es to try #nd red-&e de#t) #nd dis#'ility #nd i%,rove re&overy. Pilot st-dy re*istered -nder ISRCTN50 !74!1+ )tt,+""444.&ontrolled-tri#ls.&o%"ISRCTN50 !74!1 ISRCTN93732214 10.11 !"ISRCTN93732214

#cron$m Serial n!mber at so!rce St!d$ h$%othesis

6ore det#ils &#n 'e fo-nd #t+ )tt,+"",-'li&.-1&rn.or*.-1"Se#r&)"St-dy7et#il.#s,$8 St-dyI79134!7 6ore det#ils &#n 'e fo-nd #t )tt,+""444.)t#.#&.-1"2943 &a$ s!mmar$ :#&1*ro-nd #nd st-dy #i%s 0)en so%eone )#s # stro1e &#-sed 'y 'leedin* into t)e 'r#in 2)#e%orr)#*i& stro1e3 ,er%#nent 'r#in d#%#*e &#n o&&-r #nd res-lt in lon* ter% dis#'ility. T)ere is #lso # &)#n&e t)#t t)e 'leedin* &#n in&re#se/ 4)i&) %#y &#-se 4orse dis#'ility or 'e life t)re#tenin*. T)is )#,,ens in #,,ro$i%#tely 20-30; of )#e%orr)#*i& stro1e ,#tients. .t ,resent t)ere is no #v#il#'le tre#t%ent t)#t is effe&tive #t red-&in* t)e 'leedin* in t)e 'r#in #nd i%,rovin* t)e re&overy. In t)is tri#l/ 4e 4#nt to test 4)et)er it is ,ossi'le to *ive # dr-* 2tr#ne$#%i& #&id3 to ,eo,le in t)e first fe4 )o-rs #fter # )#e%orr)#*i& stro1e. 0e )o,e t)#t 4e 4ill 'e #'le to s)o4 t)#t *ivin* t)e dr-* %#y red-&e t)e &)#n&es of dyin* #nd 'ein* left 4it) dis#'ility #fter # )#e%orr)#*i& stro1e. In t)is tri#l/ t)e tre#t%ent 4e #re testin* is # dr-*/ tr#ne$#%i& #&id/ 4)i&) en&o-r#*es 'lood to &lot to sto, 'leedin*. Contin-ed or in&re#sed 'leedin* into t)e 'r#in 2)#e%#to%# e$,#nsion3 is not -n&o%%on in t)e first )o-rs #nd d#ys follo4in* # )#e%orr)#*i& stro1e #nd in&re#ses t)e ris1 of t)e ,#tient not re&overin* f-lly #nd 'ein* left 4it) so%e dis#'ility. Sto,,in* t)e 'leedin* in t)e first )o-rs #nd d#ys #fter stro1e 4it) %edi&ine %i*)t )el, ,#tients to re&over 'etter. Tr#ne$#%i& #&id is # tried #nd tested dr-* in ot)er %edi&#l &onditions t)#t #&ts <-i&1ly to )el, t)e 'lood to &lot #nd sto, 'leedin* '-t is not *iven ro-tinely #fter stro1e. 0e #i% to #ssess in t)is tri#l 4)#t effe&t tr#ne$#%i& #&id )#s on )o4 ,eo,le re&over #fter # )#e%orr)#*i& stro1e. 0)o &#n ,#rti&i,#te8 .d-lts 4it) #n #&-te stro1e &#-sed 'leedin* in t)e 'r#in/ 4it)in )o-rs of t)e stro1e onset. P#rti&i,#nts 4ill need to 'e #'le to &o%,lete #ll of t)e #ssess%ents/ #nd 4ill not )#ve # di#*nosis of #not)er %edi&#l &ondition t)#t is li1ely to interfere 4it) t)e tri#l 2e.*. ter%in#l illness or ,re*n#n&y3. P#rti&i,#nts &#nnot 'e ,#rti&i,#tin* in ot)er tri#ls t)#t #re testin* dr-*s. 0)#t does t)e st-dy involve8 =#&) ,#rti&i,#nt>s involve%ent in t)e st-dy 4ill l#st for 90 d#ys. 0e sele&t 4)i&) tre#t%ent yo- re&eive r#ndo%ly 2li1e tossin* # &oin3 'e&#-se t)is is )o4 %ost &lini&#l tri#ls #re &#rried o-t. (#lf t)e ,#rti&i,#nts 4ill re&eive t)e dr-* tr#ne$#%i& #&id in?e&tion #nd )#lf 4ill )#ve #n in?e&tion of s#lt 4#ter #s # d-%%y 2,l#&e'o3 tre#t%ent. T)e tre#t%ent 2eit)er tr#ne$#%i& #&id or d-%%y3 4ill 'e *iven #s #n in?e&tion #s soon #s ,ossi'le on&e ,#rti&i,#nts )#ve

de&ided t)ey 4is) to t#1e ,#rt in t)e st-dy. T)e tre#t%ent 4ill 'e *iven vi# # dri, over #,,ro$i%#tely )o-rs. @o- 4ill not 1no4 if yo- re&eived t)e dr-* or t)e d-%%y. T)e tre#t%ent 4ill 'e *iven on&e/ #nd t)en t)e tre#t%ent 4ill sto,. 7-rin* t)e ne$t 7 d#ys # n-rse 4ill &)e&1 t)e ,#rti&i,#nt>s &ondition loo1in* in ,#rti&-l#r for si*ns of side effe&ts of t)e tre#t%ent. 0e 4ill #lso re,e#t # 'r#in s&#n t)e d#y #fter t)e tre#t%ent to #ssess effe&ts of t)e tre#t%ent. 0e 4ill #s1 yo-r ,er%ission to &ont#&t ,#rti&i,#nts AP or &)e&1 4it) t)e N(S Infor%#tion Centre to &)e&1 on t)e ,#rti&i,#nt>s &ondition t)ree %ont)s #fter t)e stro1e #nd to &onfir% &ont#&t det#ils. T)e ,#rti&i,#nt 4ill t)en 'e &ont#&ted for # tele,)one &ons-lt#tion 4it) # %e%'er of t)e rese#r&) te#%. It 4ill involve #s1in* )o4 t)e ,#rti&i,#nt feels life )#s 'een #ffe&ted 'y t)e stro1e #nd so%e 'rief %e%ory tests. 0)#t #re t)e ,ossi'le 'enefits #nd ris1s of ,#rti&i,#tin*8 :e&#-se tr#ne$#%i& #&id is #lre#dy ro-tinely -sed in # n-%'er of 'leedin* &onditions/ 4e e$,e&t t)e ,otenti#l 'enefit of t)e dr-* 2sto,,in* 'leedin* in to t)e 'r#in3 to o-t4ei*) t)e lo4 ris1 of serio-s side effe&ts 2s-&) #s 'lood &lots3. (o4ever 4e do not 1no4 t)is for &ert#in #nd 4ill %onitor #ll ,#rti&i,#nts &losely for side effe&ts. Tre#t%ent 4it) #ny dr-*s &#n res-lt in ,ossi'le side effe&ts/ '-t t)e side effe&ts fro% tr#ne$#%i& #&id #re *ener#lly %ild. T)ey &#n in&l-de di#rr)oe#/ lo4 'lood ,ress-re #nd diBBiness. T)e dr-* &#n #lso so%eti%es #ffe&t &olo-r vision '-t t)is is r#re. (o4ever/ 'e&#-se t)e tre#t%ent 4or1s 'y sto,,in* 'leedin* t)ere is # &)#n&e it &#n &#-se #n in&re#se in 'lood &lot for%#tion. T)is &#n o&&-r in t)e le*s 2dee, vein t)ro%'osis/ 7CT3 or t)e l-n*s 2P-l%on#ry e%'olis%/ P=3 #nd is ,otenti#lly very serio-s #nd %#y'e even life t)re#tenin*. In # very l#r*e st-dy in 20/000 ,eo,le 4it) serio-s 'leedin*/ tr#ne$#%i& #&id 4#s s#fe #nd red-&ed t)e n-%'er of ,eo,le dyin* fro% 'leedin*. T)ere 4#s no in&re#se in serio-s side effe&ts/ s-&) #s 'lood &lots/ in t)e ,#tients 4)o 4ere tre#ted 4it) tr#ne$#%i& #&id. 0)ere is t)e st-dy r-n fro%8 T)e st-dy is 'ein* r-n fro% t)e Dniversity of Nottin*)#%/ 7ivision of Stro1e '-t is # %-lti &entre tri#l/ 4it) &entres in t)e DE #nd 4orld4ide. 0)en is t)e st-dy st#rtin* #nd )o4 lon* is it e$,e&ted to r-n for8 T)e st-dy 4ill 'e re&r-itin* 2000 ,#rti&i,#nts over 4 ye#rs/ 'et4een 6#r&) 2013 #nd Fe' 2017. 0)o is f-ndin* t)e st-dy8 T)e N#tion#l Instit-te of (e#lt) Rese#r&) 2NI(R3. 0)o is t)e %#in &ont#&t8 7r. Ni1ol# S,ri** ni1ol#.s,ri**Gnottin*)#%.#&.-1

thics a%%roval St!d$ design Co!ntries of recr!itment

NR=S Co%%ittee =#st 6idl#nds - Nottin*)#% 2/ 23rd Nove%'er 2012/ ref+ 12"=6"03!9 Pr#*%#ti& ,)#se III ,ros,e&tive do-'le 'lind r#ndo%ised ,l#&e'o &ontrolled tri#l .-str#li#/ 7en%#r1/ =*y,t/ (on* Eon*/ Indi#/ Ne4 He#l#nd/ Pol#nd/ Ro%#ni#/ Sri I#n1#/ S4eden/ Dnited Ein*do%

Disease'condition'st!d$ Stro1e domain "artici%ants - incl!sion .d-lt 2J1 ye#rs/ eit)er se$3 ,#tients 4it) #&-te ,ri%#ry criteria intr#&ere'r#l )#e%orr)#*e 2PIC(3 4it)in )o-rs of stro1e onset. 20)ere stro1e onset ti%e is -n1no4n/ t)e ti%e of 4)en l#st 1no4n 4ell 4ill 'e -sed.3 "artici%ants - excl!sion 1. P#tients 4it) intr#&ere'r#l )#e%orr)#*e se&ond#ry to criteria #nti&o#*-l#tion/ t)ro%'olysis or 1no4n -nderlyin* str-&t-r#l #'nor%#lity s-&) #s #rteri#l veno-s %#lfor%#tion/ #ne-rys%/ t-%o-r/ veno-s t)ro%'osis #s &#-se for t)e intr#&ere'r#l )#e%orr)#*e. Note it is not ne&ess#ry to e$&l-de #n -nderlyin* #'nor%#lity ,rior to enrol%ent/ '-t 4)ere # se&ond#ry &#-se of )#e%orr)#*e is 1no4n/ t)ese ,#tients s)o-ld not 'e re&r-ited. 2. P#tients for 4)o% tr#ne$#%i& #&id is t)o-*)t to 'e &ontr#indi&#ted 3. P#tients 4it) ,re%or'id de,enden&y 2%RSK43 4. P#rti&i,#tion in #not)er dr-* tri#l &on&-rrently 5. Prestro1e life e$,e&t#n&y L3 %ont)s 2e.*. #dv#n&ed %et#st#ti& &#n&er3 !. Co%# M Al#s*o4 &o%# s&#le L5 #ntici%ated start date #ntici%ated end date Stat!s of trial "atient information material Target n!mber of %artici%ants Interventions 01"02"2013 01"10"201! Nn*oin* Not #v#il#'le in 4e' for%#t/ ,le#se -se t)e &ont#&t det#ils 'elo4 to re<-est # ,#tient infor%#tion s)eet DE S#%,le SiBe+ 1300 Intr#veno-s tr#ne$#%i& #&id+ 1* lo#din* dose *iven #s 100 %ls inf-sion over 10 %in-tes/ follo4ed 'y #not)er 1* in 250 %ls inf-sed over )o-rs. Co%,#r#tor M %#t&)in* ,l#&e'o 2nor%#l s#line 0.9;3 #d%inistered 'y identi&#l re*i%en. Tr#ne$#%i& #&id/ To #ssess 4)et)er tr#ne$#%i& #&id is s#fe #nd red-&es de#t) or de,enden&y #fter ,ri%#ry intr#&ere'r#l )#e%orr)#*e 2PIC(3 7e#t) or de,enden&y 2ordin#l s)ift on %RS3 #t d#y 90 4ill 'e #n#lysed 'y intention-to-tre#t -sin* ordin#l lo*isti& re*ression 2NIR3/ 4it) #d?-st%ent for %ini%is#tion f#&tors. T)e #ss-%,tion of ,ro,ortion#l odds 4ill 'e tested -sin* t)e li1eli)ood r#tio test.

"rimar$ o!tcome meas!re(s)

Co%,#rison of tr#ne$#%i& #&id vers-s &ontrol. Secondar$ o!tcome meas!re(s) .t d#y 7 2or dis&)#r*e if sooner3/ ne-rolo*i&#l i%,#ir%ent 2NI(SS3. .t d#y 90/ dis#'ility 2:#rt)el inde$3/ O-#lity of Iife 2=-roOol3/ &o*nition/ &o*nition #nd %ood 2TICS #nd H7S3. S#fety+ de#t)/ serio-s #dverse events/ t)ro%'oe%'oli& events/ seiB-res. Costs+ len*t) of st#y in )os,it#l/ re-#d%ission/ instit-tion#lis#tion. R#diolo*i&#l effi&#&y"s#fety 2CT s&#n3+ &)#n*e in )#e%#to%# vol-%e fro% '#seline to 24 )o-rs/ )#e%#to%# lo&#tion/ #nd ne4 inf#r&tion. NI(R (e#lt) Te&)nolo*y .ssess%ent - 2(T.3 2DE3 *r#nt ref+ 11"129"109 )tt,+""ti&)-2.or*" +s Ni,ola S%rigg Dniversity P#r1 Nottin*)#% NA7 2R7 Dnited Ein*do% ni1ol#.s,ri**Gnottin*)#%.#&.-1 Dniversity of Nottin*)#% 2DE3 Rese#r&) Innov#tion Servi&es Ein*>s 6e#do4 C#%,-s Ienton I#ne Nottin*)#% NA7 2NR Dnited Ein*do% s,onsorGnottin*)#%.#&.-1 )tt,+""444.nottin*)#%.#&.-1" 15"01"2013 0!"03"2013

So!rces of f!nding Trial *ebsite "!blications Contact name .ddress City"to4n Hi,"Post&ode Co-ntry =%#il S%onsor .ddress

City"to4n Hi,"Post&ode Co-ntry =%#il S,onsor 4e'site+ Date a%%lied &ast edited

Date ISRCTN assigned 17"01"2013

STO"-#-ST. The S%ot Sign and Tranexamic #cid On "reventing ICH /ro*th - #-Stralasia Trial

T)is st-dy is &-rrently re&r-itin* ,#rti&i,#nts. Cerified 6#r&) 2013 'y N#tion#l Stro1e Rese#r&) Instit-te/ .-str#li# S,onsor+ N#tion#l Stro1e Rese#r&) Instit-te/ .-str#li# Infor%#tion ,rovided 'y 2Res,onsi'le P#rty3+ N#tion#l Stro1e Rese#r&) Instit-te/ .-str#li# Clini&#lTri#ls.*ov Identifier+ NCT01702!3! First re&eived+ N&to'er 3/ 2012 I#st -,d#ted+ 6#r&) 19/ 2013 I#st verified+ 6#r&) 2013 (istory of C)#n*es F-ll Te$t Cie4 T#'-l#r Cie4

No St-dy Res-lts Posted 7is&l#i%er (o4 to Re#d # St-dy Re&ord

P-r,ose T)e #i% of t)e st-dy is to test if intr#&ere'r#l )#e%orr)#*e 2IC(3 ,#tients 4)o )#ve &ontr#st e$tr#v#s#tion on &o%,-ted to%o*r#,)y #n*io*r#,)y/ t)e Ps,ot si*nP/ )#ve lo4er r#tes of )#e%#to%# *ro4t) 4)en tre#ted 4it) tr#ne$#%i& #&id 4it)in 4.5 )o-rs of stro1e onset/ &o%,#red to ,l#&e'o. Condition Intr#&ere'r#l (#e%orr)#*e Stro1e St-dy Ty,e+ St-dy 7esi*n+ Intervention#l .llo&#tion+ R#ndo%iBed =nd,oint Cl#ssifi&#tion+ S#fety"=ffi&#&y St-dy Intervention 6odel+ P#r#llel .ssi*n%ent 6#s1in*+ 7o-'le :lind 2S-'?e&t/ C#re*iver/ Investi*#tor/ N-t&o%es .ssesso r3 Pri%#ry P-r,ose+ Tre#t%ent STNP-.DST+ T)e S,ot Si*n #nd Tr#ne$#%i& .&id Nn Preventin* IC( Aro4t) - .DStr#l#si# Tri#l. Intervention 7r-*+ Tr#ne$#%i& .&id 7r-*+ Pl#&e'o "hase P)#se 2

Nffi&i#l Title+

Reso-r&e lin1s ,rovided 'y NI6+ Aeneti&s (o%e Referen&e rel#ted to,i&s+ CNI4.1-rel#ted 'r#in s%#ll-vessel dise#se

6edlinePl-s rel#ted to,i&s+ :r#in 7ise#ses CT S&#ns Ne-rolo*i& 7ise#ses R#s)es C#s&-l#r 7ise#ses 7r-* Infor%#tion #v#il#'le for+ Tr#ne$#%i& #&id D.S. F7. Reso-r&es F-rt)er st-dy det#ils #s ,rovided 'y N#tion#l Stro1e Rese#r&) Instit-te/ .-str#li#+ Pri%#ry N-t&o%e 6e#s-res+ IC( *ro4t) 'y 24Q3 )o-rs #s defined 'y eit)er 33; or ! %l in&re#se fro% '#seline/ #d?-sted for '#seline IC( vol-%e. [ Ti%e Fr#%e+ 24R"-3 )o-rs ] [ 7esi*n#ted #s s#fety iss-e+ No ] Se&ond#ry N-t&o%e 6e#s-res+ 6#?or t)ro%'oe%'oli& events 2%yo&#rdi#l inf#r&tion/ is&)#e%i& stro1e/ ,-l%on#ry e%'olis%3 [ Ti%e Fr#%e+ 0it)in 90R"-7 d#ys ] [ 7esi*n#ted #s s#fety iss-e+ @es ] .'sol-te IC( *ro4t) vol-%e 'y 24Q3 )o-rs/ #d?-sted for '#seline IC( vol-%e [ Ti%e Fr#%e+ 24R"-3 )o-rs ] [ 7esi*n#ted #s s#fety iss-e+ No ] .'sol-te intr#ventri&-l#r )#e%#to%# 2IC(3 *ro4t) vol-%e 'y 24Q3 )o-rs/ #d?-sted for '#seline IC( vol-%e [ Ti%e Fr#%e+ 24R"-3 )o-rs ] [ 7esi*n#ted #s s#fety iss-e+ No ] %odified R#n1in S&#le 2%RS3 s&ore of 0-4 #t 3 %ont)s [ Ti%e Fr#%e+ 90R"-7 d#ys ] [ 7esi*n#ted #s s#fety iss-e+ No ] %odified R#n1in S&#le 2%RS3 s&ore of 0-3 #t 3 %ont)s [ Ti%e Fr#%e+ 90R"-7 d#ys ] [ 7esi*n#ted #s s#fety iss-e+ No ] C#te*ori&#l s)ift in %RS #t 3 %ont)s/ s-'?e&t to t)e v#lidity of ,ro,ortion#l odds #ss-%,tion [ Ti%e Fr#%e+ 90R"-7 d#ys ] [ 7esi*n#ted #s s#fety iss-e+ No ] 7e#t) d-e to #ny &#-se 'y 3 %ont)s [ Ti%e Fr#%e+ 4it)in 90R"-7 d#ys ] [ 7esi*n#ted #s s#fety iss-e+ No ] Nt)er N-t&o%e 6e#s-res+ IC( *ro4t) [ Ti%e Fr#%e+ 24R"-3 )o-rs ] [ 7esi*n#ted #s s#fety iss-e+ No ] =$,lor#tory #n#lyses 4ill 'e r-n 4it) #d?-st%ents for '#seline v#ri#'les s-&) #s #*e/ Al#s*o4 Co%# S&#le 2ACS3/ ,resen&e of IC(/ #nd IC( lo&#tion/ #nd in t)e follo4in* s-'*ro-,s+ onset-to-tre#t%ent ti%e 2L3 vs. K3 )o-rs3S '#seline IC( vol-%e 2L30 vs. K30 %l3S #n#to%i&#l lo&#tion 2dee,/ lo'#r/ or &ere'ell#r3S IC( 2#'sent vs. ,resent3S ACS 2K12 vs. -123 #nd #*e 2L70 vs. K703. T)ese #n#lyses 4ill 'e )y,ot)esis *ener#tin*/ #s t)e tri#l is not ,o4ered for t)e%.

%odified R#n1in S&#le 2%RS3 [ Ti%e Fr#%e+ 90R"-7 d#ys ] [ 7esi*n#ted #s s#fety iss-e+ No ] =$,lor#tory #n#lyses 4ill 'e r-n 4it) #d?-st%ents for '#seline v#ri#'les s-&) #s #*e/ Al#s*o4 Co%# S&#le 2ACS3/ ,resen&e of IC(/ #nd IC( lo&#tion/ #nd in t)e follo4in*

s-'*ro-,s+ onset-to-tre#t%ent ti%e 2L3 vs. K3 )o-rs3S '#seline IC( vol-%e 2L30 vs. K30 %l3S #n#to%i&#l lo&#tion 2dee,/ lo'#r/ or &ere'ell#r3S IC( 2#'sent vs. ,resent3S ACS 2K12 vs. -123 #nd #*e 2L70 vs. K703. T)ese #n#lyses 4ill 'e )y,ot)esis *ener#tin*/ #s t)e tri#l is not ,o4ered for t)e%.

=sti%#ted =nroll%ent+ St-dy St#rt 7#te+ =sti%#ted St-dy Co%,letion 7#te+ =sti%#ted Pri%#ry Co%,letion 7#te+

100 7e&e%'er 2012 7e&e%'er 2014 Se,te%'er 2014 2Fin#l d#t# &olle&tion d#te for ,ri%#ry o-t&o%e %e#s-re3 #ssigned Interventions 7r-*+ Tr#ne$#%i& .&id

#rms .&tive Co%,#r#tor+ Tr#ne$#%i& .&id Intr#veno-s tr#ne$#%i& #&id 1000 %* in 100 %I 0.9; N#Cl over 10 %in-tes follo4ed 'y 1000 %* in 500 %I 0.9; N#Cl inf-sion over )o-rs. Pl#&e'o Co%,#r#tor+ Pl#&e'o Intr#veno-s ,l#&e'o in 100 %I 0.9; N#Cl over 10 %in-tes follo4ed 'y 500 %I 0.9; N#Cl inf-sion over )o-rs.

7r-*+ Pl#&e'o

=li*i'ility .*es =li*i'le for St-dy+ Aenders =li*i'le for St-dy+ .&&e,ts (e#lt)y Col-nteers+ Criteri# In&l-sion Criteri#+

1 @e#rs #nd older :ot) No

P#tients ,resentin* 4it) #n #&-te IC( Contr#st e$tr#v#s#tion 4it)in t)e )#e%orr)#*e/ Ps,ot si*nP/ ev#l-#ted fro% t)e CT. #&&ordin* to t)ree &riteri#/ #ll of 4)i&) %-st 'e ,resent+ 1. Ser,i*ino-s or s,ot-li1e #,,e#r#n&e 4it)in t)e %#r*in of # ,#ren&)y%#l )#e%#to%# 4it)o-t &onne&tion to #n o-tside vesselS 2. T)e density 2in (o-nsfield -nits3 s)o-ld 'e *re#ter t)#n t)#t of t)e '#&1*ro-nd )#e%#to%# 2site investi*#tors #re not re<-ired to do&-%ent t)e density3S #nd 3. No )y,erdensity #t t)e &orres,ondin* lo&#tion on non-&ontr#st CT. .*e J1 ye#rs

Tre#t%ent &#n &o%%en&e 4it)in 1 )o-r of initi#l CT #nd 4it)in 4.5 )o-rs of sy%,to% onset 2or in ,#tients 4it) -n1no4n ti%e of sy%,to% onset/ t)e ti%e ,#tient 4#s l#st 1no4n to 'e 4ell3 Infor%ed &onsent )#s 'een re&eived in #&&ord#n&e to lo&#l et)i&s &o%%ittee re<-ire%ents

=$&l-sion Criteri#+

Al#s*o4 &o%# s&#le 2ACS3 tot#l s&ore of L :r#inste% IC( IC( vol-%e K70 %l #s %e#s-red 'y t)e .:C"2 %et)od IC( 1no4n or s-s,e&ted 'y st-dy investi*#tor to 'e se&ond#ry to tr#-%#/ #ne-rys%/ v#s&-l#r %#lfor%#tion/ )#e%orr)#*i& tr#nsfor%#tion of is&)#e%i& stro1e/ &ere'r#l veno-s t)ro%'osis/ t)ro%'olyti& t)er#,y/ t-%or/ or infe&tion Contr#st #lre#dy #d%inistered 4it)in 24 )o-rs ,rior to initi#l CT or &ontr#indi&#tion to i%#*in* 4it) CT &ontr#st #*ents 2e.*. 1no4n or s-s,e&ted iodine #ller*y or si*nifi&#nt ren#l f#il-re3 .ny )istory or &-rrent eviden&e s-**estive of veno-s or #rteri#l t)ro%'oti& events 4it)in t)e ,revio-s 12 %ont)s/ in&l-din* &lini&#l/ =CA/ l#'or#tory/ or i%#*in* findin*s. Clini&#lly silent &)#n&e findin*s of old is&)e%i# #re not &onsidered e$&l-sion. Pre-stro1e %odified R#n1in S&#le 2%RS3 s&ore of K2 (eredit#ry or #&<-ired )#e%orr)#*i& di#t)esis or &o#*-l#tion f#&tor defi&ien&y. Dse of )e,#rin/ lo4-%ole&-l#r 4ei*)t )e,#rin/ APII'"III# #nt#*onist/ or or#l #nti&o#*-l#tion 2e.*. 4#rf#rin/ f#&tor T# in)i'itor/ t)ro%'in in)i'itor3 4it)in t)e ,revio-s 14 d#ys/ irres,e&tive of l#'or#tory v#l-es Pre*n#n&y 24o%en of &)ild'e#rin* ,otenti#l %-st 'e tested3 Pl#nned s-r*ery for IC( 4it)in 24 )o-rs Con&-rrent or ,l#nned tre#t%ent 4it) )#e%ost#ti& #*ents 2e.*. ,rot)ro%'in &o%,le$ &on&entr#te/ vit#%in E/ fres) froBen ,l#s%#/ or ,l#telet tr#nsf-sion3 P#rti&i,#tion in #ny investi*#tion#l st-dy in t)e l#st 30 d#ys Eno4n ter%in#l illness or ,l#nned 4it)dr#4#l of &#re or &o%fort &#re %e#s-res. .ny &ondition t)#t/ in t)e ?-d*%ent of t)e investi*#tor &o-ld i%,ose )#B#rds to t)e ,#tient if st-dy t)er#,y is initi#ted or #ffe&t t)e ,#rti&i,#tion of t)e ,#tient in t)e st-dy.

Cont#&ts #nd Io&#tions Ple#se refer to t)is st-dy 'y its Clini&#lTri#ls.*ov identifier+ NCT01702!3! Cont#&ts Cont#&t+ .tte 6ereto?#/ 67 Io&#tions .-str#li#/ Ne4 So-t) 0#les Aosford (os,it#l Not yet re&r-itin* E#n4#l/ Ne4 So-t) 0#les/ .-str#li#/ 2259 Prin&i,#l Investi*#tor+ Uon#t)#n St-r%/ 67 R!1 3 9342 443 #tte.%ereto?#G-ni%el'.ed-.#-

Uo)n (-nter (os,it#l Re&r-itin* Ne4&#stle/ Ne4 So-t) 0#les/ .-str#li#/ 2310 Prin&i,#l Investi*#tor+ Neil S,r#tt St. Cin&entVs (os,it#l Not yet re&r-itin* Sydney/ Ne4 So-t) 0#les/ .-str#li#/ 2010 Prin&i,#l Investi*#tor+ Ro%es) 6#r1-s Roy#l Prin&e .lfred (os,it#l Not yet re&r-itin* Sydney/ Ne4 So-t) 0#les/ .-str#li#/ 2050 Prin&i,#l Investi*#tor+ C#ndi&e 7el&o-rt 0est%e#d (os,it#l Not yet re&r-itin* 0est%e#d/ Ne4 So-t) 0#les/ .-str#li#/ 2145 Prin&i,#l Investi*#tor+ Neil 6#)#nt .-str#li#/ So-t) .-str#li# O-een =liB#'et) (os,it#l Not yet re&r-itin* .del#ide/ So-t) .-str#li#/ .-str#li#/ 5011 Prin&i,#l Investi*#tor+ Ui% U#nnes Roy#l .del#ide (os,it#l Not yet re&r-itin* .del#ide/ So-t) .-str#li#/ .-str#li#/ 5000 Prin&i,#l Investi*#tor+ Ti%ot)y Eleini* Iyell 6&=4in (os,it#l Not yet re&r-itin* .del#ide/ So-t) .-str#li#/ .-str#li#/ 5112 Prin&i,#l Investi*#tor+ Ti%ot)y Eleini* Flinders 6edi&#l Centre Not yet re&r-itin* :edford P#r1/ So-t) .-str#li#/ .-str#li#/ 5042 Prin&i,#l Investi*#tor+ .ndre4 Iee .-str#li#/ Ci&tori# :o$ (ill (os,it#l Re&r-itin* :o$ (ill/ Ci&tori#/ .-str#li#/ 312 Prin&i,#l Investi*#tor+ C)risto,)er :l#din Nort)ern (os,it#l Not yet re&r-itin* =,,in*/ Ci&tori#/ .-str#li#/ 307! Prin&i,#l Investi*#tor+ Uor*e H#v#l# 0estern (os,it#l Not yet re&r-itin* Foots&r#y/ Ci&tori#/ .-str#li#/ 3011 Prin&i,#l Investi*#tor+ Tiss# 0i?er#tne Fr#n1ston (os,it#l Not yet re&r-itin* Fr#n1ston/ Ci&tori#/ .-str#li#/ 3199 Prin&i,#l Investi*#tor+ U#y#nt)# R-,#sin*)e .lfred (os,it#l Not yet re&r-itin* 6el'o-rne/ Ci&tori#/ .-str#li#/ 3004 Prin&i,#l Investi*#tor+ Uor*e H#v#l# T)e Roy#l 6el'o-rne (os,it#l Re&r-itin*

6el'o-rne/ Ci&tori#/ .-str#li#/ 3050 Prin&i,#l Investi*#tor+ Ste,)en 6 7#vis S,onsors #nd Coll#'or#tors N#tion#l Stro1e Rese#r&) Instit-te/ .-str#li# Investi*#tors Prin&i,#l Investi*#tor+ Ste,)en 6 7#vis/ 67 6el'o-rne (e#lt) T)e Florey Instit-te of Ne-ros&ien&e #nd 6ent#l (e#lt)

Prin&i,#l Aeoffrey . 7onn#n/ Investi*#tor+ 67 6ore Infor%#tion No ,-'li&#tions ,rovided Res,onsi'le P#rty+ Clini&#lTri#ls.*ov Identifier+ Nt)er St-dy I7 N-%'ers+ St-dy First Re&eived+ I#st D,d#ted+ (e#lt) .-t)ority+

N#tion#l Stro1e Rese#r&) Instit-te/ .-str#li# NCT01702!3! NT.1201 N&to'er 3/ 2012 6#r&) 19/ 2013 .-str#li#+ 7e,#rt%ent of (e#lt) #nd .*ein* T)er#,e-ti& Aoods .d%inistr#tion (istory of C)#n*es

Eey4ords ,rovided 'y N#tion#l Stro1e Rese#r&) Instit-te/ .-str#li#+ Intr#&ere'r#l (e%orr)#*e Fi'rin 6od-l#tin* .*ents IC( P)#r%#&olo*i& .&tions Stro1e C#rdiov#s&-l#r .*ents Cere'rov#s&-l#r 7isorders T)er#,e-ti& Dses :r#in 7ise#ses (e%#tolo*i& .*ents Centr#l Nervo-s Syste% 7ise#ses (e%ost#ti&s Nervo-s Syste% 7ise#ses Contr#st 6edi# C#s&-l#r 7ise#ses .n*io*r#,)y C#rdiov#s&-l#r 7ise#ses Cere'r#l .n*io*r#,)y Tr#ne$#%i& .&id To%o*r#,)y/ T-R#y Co%,-ted .ntifi'rinolyti& .*ents .ddition#l relev#nt 6eS( ter%s+ (e%orr)#*e Stro1e Cere'r#l (e%orr)#*e P#t)olo*i& Pro&esses Cere'rov#s&-l#r 7isorders :r#in 7ise#ses Centr#l Nervo-s Syste% 7ise#ses Nervo-s Syste% 7ise#ses C#s&-l#r 7ise#ses C#rdiov#s&-l#r 7ise#ses Intr#&r#ni#l (e%orr)#*es .ntifi'rinolyti& .*ents Tr#ne$#%i& .&id C#rdiov#s&-l#r .*ents Fi'rin 6od-l#tin* .*ents 6ole&-l#r 6e&)#nis%s of P)#r%#&olo*i&#l .&tion P)#r%#&olo*i& .&tions (e%ost#ti&s Co#*-l#nts (e%#tolo*i& .*ents T)er#,e-ti& Dses

Clini&#lTri#ls.*ov ,ro&essed t)is re&ord on Nove%'er 2!/ 2013