Ch inJIn teg r Med
•1•
OR IG INALART ICLE ARandom i zedT r ia ltoAssesstheLong -Te rmSa fe tyo fNeu roA iD amongCaucas ianPa t ien tsw i thAcu teIschem icS t roke 1 1 RezaBavasa rdshah r ipou r1,2,AhmadHema t i ,andAnaHosse inzadeh ma lek i
j e c t iv e: e:Toassessthelong ABSTRACT Ob te rm(upto6 mon ths )sa fe typ ro f i leo fa3 -mon threg imeno f e thod s:Ato s: Neu roA iDfo racu teischem ics t roke .M ta lo f190pa t ien ts w i thacu teischem ics t roke we reiden t i fied fo re l ig ib i l i tyinarandom ized ,doub le -b l ind ,p lacebo -con t ro l ledc l in ica lt r ia l ,o f wh ich150pa t ien tsa l loca tedto e i the rrece iv ing Neu roA iD(80cases )o rp lacebo(70cases ) we reana lyzeda f te rd ropou tsduetoabsenceo f base l ineda ta ,ea r lydea th ,o rnoncomp l iance . Bo thg roupsrece ivedt rea tmen tfo rth ree mon thsandfo l lowed upfo rano the rth ree mon thsa f te rthecomp le t iono fthet rea tmen t . Occu r renceo fc l in ica ladve rseeven tsand labo ra to rypa rame te rs we reassesseda t1 mon th ,3 mon ths(wh i leunde rt rea tmen t )and6 mon ths(3 mon ths a f te rthecomp le t iono ft rea tmen t ) .S ta t is t ica lcompa r isonsbe tweeng roupswe repe r fo rmedus ingch i -squa retes t e su l t s:Thetwog o rt tes t wheneve rapp rop r ia te .R roupshadcompa rab lebase l inecha rac te r is t ics .M i ldnausea was mo recommon lyrepo r tedinpa t ien tstak ing Neu roA idcompa red w i thp lacebo(P=0 .01 ) ,o f wh ich9ou to f 10 we reobse rvedon lydu r ingthefirs t mon tho ft rea tmen t . Howeve r ,noneo ftheadve rseeven tsrepo r ted we re cons ide redseve reo rrequ i redd iscon t inua t iono fthes tudyd rug .The re wasnos ign i f ican tchangeobse rved in meana r te r ia lb loodp ressu re ,haemog lob in ,rena landl ive rlabo ra to rypa rame te rsdu r ingt rea tmen tw i th C o n c l u s i o n Neu roA idandupto3 mon thsa f te rcomp le t iono fa3 -mon threg imen . :Neu roA iDissa feanddoesno t a f fec thema to log ic ,hepa t ic ,andrena lfunc t ionsdu r ingandlonga f te rcomp le t iono ft rea tmen t . KEYWORDS s t roke ,Neu roA id ,sa fe ty
S t rokeisalead ingcauseo fdea thandch ron ic d isab i l i ty wo r ldw ide .(1) E f fec t ivep rovent rea tmen ts fo rs t roke ,howeve r ,havebeenl im i ted . Duetothe comp lex i tyo fthed isease ,thesea rchfo rt rea tmen ts wh ichspec ifica l lyac tonas ing leta rge t mechan ism toreducelong te rmd isab i l i tyhascons tan t lyfa i led , lead ingto op in ionstha tcomb ina t ionthe rap ies comp r is ing mo rethanoneac t iveing red ien t may (2 ,3 ) rep resen t a be t te rs t ra tegy aga ins ts t roke . Neu roA iD , a Ch inese med ic inetha t has been deve lopedto a idpos t -s t rokerecove ry ,issucha the rapy w i th mu l t ip le mechan ismsandisthesub jec t o fala rgec l in ica lt r ia l .(4-6)
(7 -9 ) Fu r the rmo re ,i thasbeen t rea teda f te ras t roke . showntobesa feanddoesno t mod i fyhaemos tas is , haema to log yandb io chem i s t r y inbo thno rma lsub je c t s ands t rokepa t ien ts wheng ivenacu te lyandinthe subacu tes tages .(10,11) Howeve r ,long te rmsa fe tyda ta issca rce .Fu r the rmo re ,the reisnoda taoni tssa fe ty amongCaucas ians .
We ,the re fo re ,a imedtoassessthesa fe tyo f Neu roA iDupto6 mon thsf roms ta r to ftheth ree mon tht rea tmen tcou rsefo rs t roke .
METHODS S tudyDes ign
Neu roA iDcomposeso fn inehe rba l( inc lud ing Rad ixas t raga l i,Rad ixsa lv ia m i l t io r rh izae,Rad ix paeon iaerub ra, Rh i zomachuan x iong, Rad i xange l i cae s inens is,Ca r thamust inc to r ius,P runuspe rs ica,Rad ix po lyga lae andRh izomaaco r ita ta r inow i i)andf ive an ima lcomponen ts( inc lud ingH i rudo,Eupo lyphaga seus te leophaga,Ca lcu lusbov isa r t i fac tus,Bu thus (5 ) ma r tens i i andCo rnusa igaeta ta r icae) . P re l im ina ry s tud ieshaveshownp rom is ingresu l tso f Neu roA id 's e f f icacyontherecove ryo findependence , mo to r func t ion ,v is ionandcogn i t iveab i l i t iesinpa t ien ts
Th isisarandom izeddoub le -b l indp lacebo con t ro l ledc l in ica lt r ia l( IRCT :138905103663N2 ) .
©The Ch ineseJou rna lo fIn teg ra tedT rad i t iona land Wes te rn Med ic ineP ressandSp r inge r -Ve r lagBe r l inHe ide lbe rg2014 Suppo r tedbyfundsf romtheJound ishapou r Med ica lUn ive rs i ty 1 . Depa r tmen to f Neu ro logy , Ahvaz Un ive rs i tyo f Med ica l Sc iences , Ahvaz , Khuzes tan ,I ran ;2 . Comp rehens ive S t roke Cen te r , Depa r tmen to f Neu ro logy , Un ive rs i tyo fA labamaa t B i rm ingham ,B i rm ingham ,AL ,USA Co r respondenceto :D r . Reza Bavasa rdshah r ipou r , Te l : 1 -205 -201 -4269 ,E -ma i l :nbava r@yahoo .com DO I :10 .1007 /s11655 -014 -1687 -8
Ch inJIn teg r Med
•2•
Inc lus ionC r i te r ia Werec ru i tedpa t ien tsagedbe tween55and90 yea rso ld w i thacu teischem ics t rokeinthe m idd le , an te r io r ,o rpos te r io rce reb ra la r te r iesand Na t iona l Ins t i tu teo f Hea l th S t roke Sca le(N IHSS )sco reo f a tleas t5 , who we readm i t teda t Go les tan Hosp i ta l , Ka ram i Hosp i ta l ,o r Emam Hosp i ta l(a l linI ran ) be tweenFeb rua ry2010toJune2010andcon f i rmed b yneu ro imag ing[e i the rcompu tedtomog raph y(CT )o r magne t i cre sonan ceimag ing(MR I ) ]w i th inonewee ko f random i za t ion . On l ythenewle s ion s we recon s ide red toberespons ib lefo rtheindexs t rokea tthet imeo f e l ig ib i l i t ya sseenontheba se l ine imag ing(CTo r MR I ) .
Exc lus ionC r i te r ia Weexc ludedpa t ien ts who we readm i t tedto thein tens iveca reun i t(astheya re mo rep roneto comp l ica t ions ) ,hadin t race reb ra lhaemo r rhageo r haemo r rhag icconve rs ion ,hadh is to ryo fp rev ious s t rokeo rev idenceo fp re -ex is t ings t rokeonb ra in imag ing ,hads ign i fican tsys tem icd isease ,i .e .ch ron ic obs t ruc t ive pu lmona ry d isease(COPD ) ,seve re a s thma ,CO2 na r co s i s ,rena lfa i lu re ,se ve reconge s t i ve hea r tfa i lu re ,u raem ia ,c i r rhos is , psychos is , demen t ia ,andb ra inpa tho log ieso the rthans t roke (e .g .p r ima ryb ra intumou rs , me tas tas iso rin fec t ious les ions ) ,andhadpa r t ic ipa tedinano the rc l in ica lt r ia l w i th in3 mon thso finc lus ion .
One to -onet rea tmen ta l loca t ion waspe r fo rmed acco rd ingtoacompu te r -gene ra tedrandom iza t ion l is tp repa reda tthes ta r to fthes tudy ,kep tind iv idua l ly sea led by an appo in teds tudys ta f f , andopened uponiden t i f ica t iono fane l ig ib lepa t ien t .A l lpa t ien ts rece iveds tanda rdt rea tmen tfo rs t roke ,inc lud ingan t i th rombo t i cthe rap y ,s ta t in ,b loodp re s su recon t ro l ,an t i d iabe t ic med ica t ions ,ando the rt rea tmen tsdeemed med ica l lynecessa ry .
Obse rva t ionI tems Base l inein fo rma t ioninc lud ingage ,gende r , race ,h is to ryo fhype r tens ion ,d iabe tes me l l i tus ,o r hype r l ip idem ia ,N IHSS ,ce reb ra la r te ryinvo lved , T r ia lo fO rganon10172in Acu te S t roke T rea tmen t (TOAST )c lass i fica t ion ,andlabo ra to rytes tsresu l tsfo r haemog lob in ,b loodu rean i t rogen(BUN ) ,c rea t in ine , sod ium ,po tass ium ,a lan inet rans fe rase(ALT ) ,and aspa r ta team ino t rans fe rase(AST ) we reco l lec ted . N IHSS and mod i f ied Rank in Sca le(mRS ) we re pe r formeda t3 mon ths(a tcomp le t iono ft rea tmen t ) . Pa t ien ts we re mon i to redfo r6 mon thsandda taon b loodp re s su re ,haemog lob in ,BUN ,c rea t in ine ,sod ium , po tass ium ,as we l lasoccu r renceo fadve rseeven ts , we reco l lec teda t1 ,3 ,and6 mon ths(3 mon thsa f te r comp le t iono ft rea tmen t ) .
In fo rmedconsen ts we re ob ta inedf rom a l l pa r t i c ipan t sa sapp ro vedb ythee th i c scomm i t teeo fthe Jound i shapou r Med i ca l Un i ve r s i t y wh i chi sre spon s ib le fo rtheth reeho sp i ta l s in vo l ved inth i ss tud y .
Thefo l low ingno rma lrange swe reu sedtoa s se s s whe the rb loodpa rame te rva lues we reabno rma l : meana r te r ia lb loodp re s su re(MABP )60–110 mm Hg , haemog lob in12–7g /dL , BUN8–25 mg /dL ,c rea t in ine 0 .6–1 .5 mg /dL ,sod ium135–145 mEq /L ,po tass ium 3 .5–5 .5 mEg /L ,ALT7–56U /L ,andAST5–40U /L .
In te rven t ions
S ta t is t ica lAna lys is
E l ig ib lepa t ien t swe rerandom l ya l lo ca tedtoe i the r re ce i v ingNeu roA iDo rp la ceboa sanadd -ont rea tmen t w i th inthef i rs t weeka f te rthes t rokea tadoseo f4 capsu les3t imesadayfo r3 mon ths . Pa t ien ts who requ i redtubefeed ing we reg i venthes tud yt rea tmen t b yopen ingthecap su le sandadm in i s te r ingthed i lu ted powde rcon ten t sth roughthetube .
Summa ry da ta we rerepo r ted as numbe rs andp ropo r t ionsfo rca tego r ica lva r iab lesandas mean±s tanda rddev ia t ionsfo rcon t inuousva r iab les . Wheneve rapp rop r ia te ,compa r isonsbe tweeng roups we repe r fo rmedus ingch i -squa retes t(o rF ishe r 's exac ttes tincaseso fce l lshav inglessthanthe expec tednumbe ro fobse rva t ions )fo rca tego r ica l va r iab les , andt tes t(o r ANOVAfo rrepea ted measu res )fo rcon t inuousva r iab letocompu tefo r s ta t is t ica ls ign ificance . AP va luelessthan0 .05 was cons ide reds ign ifican td i f fe rence .
Neu roA iDand ma tch ingp lacebo wassupp l ied bythe Go les tan Hosp i ta lpha rmacyasfundedby the un ive rs i ty . Neu roA iD was manu fac tu red by Mo leac(S ingapo re ) whe reeachba tcho fthep roduc t unde rwen tin -p rocessandf in ishedp roduc tqua l i ty con t ro lfo rbo thsa fe tyande f ficacyus ings tanda rd ized assays .
RESULTS Pa t ien tsInc lus ionandBase l ineCha rac te r is t ics N ine ty f ivepa t ien ts we reiden t i f iedfo reach
Ch inJIn teg r Med
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Pa t ien tsw i thacu teischem ics t roke w i th in1weeko fonse t(190cases )
A l lo ca tedtoNeu roA iD(95ca se s )
A l loca tedtop lacebo(95cases )
Ba se l inec l in i ca land labo ra to r yda ta no tdonefo rva r iedrea son s(2ca se s )
Ba se l inec l in i ca land labo ra to r yda ta no tdone fo rva r iedrea son s(16ca se s )
Pa t ien t ss ta r tedonNeu roA iDand hadba se l ineda ta(93ca se s )
Pa t ien t ss ta r tedonp la ceboand hadba se l ineda ta(79ca se s )
D iedf roms t roke(hem ia t ion ) w i th in2weeks(3cases )
D iedf roms t roke(hem ia t ion ) w i th in2weeks(3cases )
Non -comp l ian tandlos tto fo l lowup(10cases )
Non -comp l ian tandlos tto fo l lowup(6cases )
Pa t ien tsonNeu roA iDandab le tofo l lowup(80cases )
Pa t ien tsonp laceboandab le tofo l lowup(70cases )
Pa t ien t scomp l ian tw i thNeu roA iD fo r3 mon th sandfo l lowedupa t 1 mon th ,3 mon th s ,and 6 mon th s(80ca se s )
Pa t ien t scomp l ian tw i thp la cebo fo r3 mon th sandfo l lowedupa t 1 mon th ,3 mon th s ,and 6 mon th s(70ca se s )
F igu re2 . S tudyF lowcha r t
t rea tmen ta rm ,bu t18pa t ien ts(2inthe Neu roA iD g roupand16inthep lacebog roup ) we reunab le tocomp ly w i thbase l inerequ i remen tsfo rc l in ica l andlabo ra to ryda tafo rva r iedreasons ,inc lud ing unava i lab i l i tyo fin fo rma t ionf romre fe r r inghosp i ta l , pa t ien tre fusa l ,and m issedp rocedu resbynon -s tudy s ta f f .N ine ty th reepa t ien tshadbase l ineda taand we res ta r tedonNeu roA iDand79pa t ien t sonp la cebo . Th reepa t ien tsineachg roupd ied w i th in2 weekso f s t rokeonse t .Thesedea ths we redeemedtobedue
totheunde r ly ingseve res t rokeandresu l t ingce reb ra l he rn ia t ion . Amongtherema in ingpa t ien ts ,16had poo rfo l low -upcomp l ianceandda tawe reava i lab lefo r ana lys isin150pa t ien ts(80pa t ien tsonNeu roA iDand 70pa t ien t sonp la cebo ) .Amongthe se150pa t ien t s ,a l l we recomp l ian ttothea l loca tedt rea tmen t ,noned ied , anda l lwe reab letofo l lowupfo rthe1 ,3and6 -mon th s a s se s smen t s(F igu re1 ) .A l lpa t ien t swe reCau ca s ian s . Base l inecha rac te r is t ics we res im i la rbe tweenthetwo g roups(Tab le1 ) .
Tab le1 . Base l ineCha rac te r is t icso fCoho r t I tem
Neu roA idg roup(80cases )
–
P lacebog roup(70cases )
P-va lue
r ) Age(x±s,yea
76 .7±8 .7
75 .9±7 .8
ns
Fema legende r(Case ,% )
38(48 )
30(43 )
ns
R iskfac to r(Case ,% ) Hype r tens ion
53(66 )
51(73 )
ns
D iabe tes me l l i tus
39(49 )
29(41 )
ns
Hype r l ip idem ia
40(50 )
30(43 )
ns
16 .3±3 .5
16 .6±3 .8
ns ns
– ±s,sco re ) N IHSS(x
Ce reb ra la r te rya f fec ted(Case ,% ) M idd lece reb ra la r te ry
40(50 )
33(47 )
An te r io rce reb ra la r te ry
20(25 )
15(22 )
Pos te r io rce reb ra la r te ry
20(25 )
22(31 )
61(76 )
52(74 )
9(11 )
12(17 )
10(12 )
6(9 )
TOASTc lass ifica t ion(Case ,% ) La rgevesse ld isease Ca rd ioembo l ism Sma l lvesse ld isease No te :ns ,no ts ta t is t ica l lys ign ifican td i f fe rence
ns
0 .87
0
3
25 .3±6 .1
0
0 .4 ±6 .5
24 .0±5 .7
0
0 .1 ±0 .5
4 .4±0 .4
0
–1 .0±5 .5
25 .4±5 .9
0
–0 .6±6 .1
24 .2±5 .6
0
–0 .0±0 .6
4 .4±0 .5
16
–0 .8±5 .3
140 .2±3 .9
0 .95
0 .86
0 .89
0 .95
0 .31
0 .81
0 .95
0 .31
0 .42
0 .83
0 .88
0 .99
0 .95
0 .52
0 .19
0 .67
•1•
OR IG INALART ICLE ARandom i zedT r ia ltoAssesstheLong -Te rmSa fe tyo fNeu roA iD amongCaucas ianPa t ien tsw i thAcu teIschem icS t roke 1 1 RezaBavasa rdshah r ipou r1,2,AhmadHema t i ,andAnaHosse inzadeh ma lek i
j e c t iv e: e:Toassessthelong ABSTRACT Ob te rm(upto6 mon ths )sa fe typ ro f i leo fa3 -mon threg imeno f e thod s:Ato s: Neu roA iDfo racu teischem ics t roke .M ta lo f190pa t ien ts w i thacu teischem ics t roke we reiden t i fied fo re l ig ib i l i tyinarandom ized ,doub le -b l ind ,p lacebo -con t ro l ledc l in ica lt r ia l ,o f wh ich150pa t ien tsa l loca tedto e i the rrece iv ing Neu roA iD(80cases )o rp lacebo(70cases ) we reana lyzeda f te rd ropou tsduetoabsenceo f base l ineda ta ,ea r lydea th ,o rnoncomp l iance . Bo thg roupsrece ivedt rea tmen tfo rth ree mon thsandfo l lowed upfo rano the rth ree mon thsa f te rthecomp le t iono fthet rea tmen t . Occu r renceo fc l in ica ladve rseeven tsand labo ra to rypa rame te rs we reassesseda t1 mon th ,3 mon ths(wh i leunde rt rea tmen t )and6 mon ths(3 mon ths a f te rthecomp le t iono ft rea tmen t ) .S ta t is t ica lcompa r isonsbe tweeng roupswe repe r fo rmedus ingch i -squa retes t e su l t s:Thetwog o rt tes t wheneve rapp rop r ia te .R roupshadcompa rab lebase l inecha rac te r is t ics .M i ldnausea was mo recommon lyrepo r tedinpa t ien tstak ing Neu roA idcompa red w i thp lacebo(P=0 .01 ) ,o f wh ich9ou to f 10 we reobse rvedon lydu r ingthefirs t mon tho ft rea tmen t . Howeve r ,noneo ftheadve rseeven tsrepo r ted we re cons ide redseve reo rrequ i redd iscon t inua t iono fthes tudyd rug .The re wasnos ign i f ican tchangeobse rved in meana r te r ia lb loodp ressu re ,haemog lob in ,rena landl ive rlabo ra to rypa rame te rsdu r ingt rea tmen tw i th C o n c l u s i o n Neu roA idandupto3 mon thsa f te rcomp le t iono fa3 -mon threg imen . :Neu roA iDissa feanddoesno t a f fec thema to log ic ,hepa t ic ,andrena lfunc t ionsdu r ingandlonga f te rcomp le t iono ft rea tmen t . KEYWORDS s t roke ,Neu roA id ,sa fe ty
S t rokeisalead ingcauseo fdea thandch ron ic d isab i l i ty wo r ldw ide .(1) E f fec t ivep rovent rea tmen ts fo rs t roke ,howeve r ,havebeenl im i ted . Duetothe comp lex i tyo fthed isease ,thesea rchfo rt rea tmen ts wh ichspec ifica l lyac tonas ing leta rge t mechan ism toreducelong te rmd isab i l i tyhascons tan t lyfa i led , lead ingto op in ionstha tcomb ina t ionthe rap ies comp r is ing mo rethanoneac t iveing red ien t may (2 ,3 ) rep resen t a be t te rs t ra tegy aga ins ts t roke . Neu roA iD , a Ch inese med ic inetha t has been deve lopedto a idpos t -s t rokerecove ry ,issucha the rapy w i th mu l t ip le mechan ismsandisthesub jec t o fala rgec l in ica lt r ia l .(4-6)
(7 -9 ) Fu r the rmo re ,i thasbeen t rea teda f te ras t roke . showntobesa feanddoesno t mod i fyhaemos tas is , haema to log yandb io chem i s t r y inbo thno rma lsub je c t s ands t rokepa t ien ts wheng ivenacu te lyandinthe subacu tes tages .(10,11) Howeve r ,long te rmsa fe tyda ta issca rce .Fu r the rmo re ,the reisnoda taoni tssa fe ty amongCaucas ians .
We ,the re fo re ,a imedtoassessthesa fe tyo f Neu roA iDupto6 mon thsf roms ta r to ftheth ree mon tht rea tmen tcou rsefo rs t roke .
METHODS S tudyDes ign
Neu roA iDcomposeso fn inehe rba l( inc lud ing Rad ixas t raga l i,Rad ixsa lv ia m i l t io r rh izae,Rad ix paeon iaerub ra, Rh i zomachuan x iong, Rad i xange l i cae s inens is,Ca r thamust inc to r ius,P runuspe rs ica,Rad ix po lyga lae andRh izomaaco r ita ta r inow i i)andf ive an ima lcomponen ts( inc lud ingH i rudo,Eupo lyphaga seus te leophaga,Ca lcu lusbov isa r t i fac tus,Bu thus (5 ) ma r tens i i andCo rnusa igaeta ta r icae) . P re l im ina ry s tud ieshaveshownp rom is ingresu l tso f Neu roA id 's e f f icacyontherecove ryo findependence , mo to r func t ion ,v is ionandcogn i t iveab i l i t iesinpa t ien ts
Th isisarandom izeddoub le -b l indp lacebo con t ro l ledc l in ica lt r ia l( IRCT :138905103663N2 ) .
©The Ch ineseJou rna lo fIn teg ra tedT rad i t iona land Wes te rn Med ic ineP ressandSp r inge r -Ve r lagBe r l inHe ide lbe rg2014 Suppo r tedbyfundsf romtheJound ishapou r Med ica lUn ive rs i ty 1 . Depa r tmen to f Neu ro logy , Ahvaz Un ive rs i tyo f Med ica l Sc iences , Ahvaz , Khuzes tan ,I ran ;2 . Comp rehens ive S t roke Cen te r , Depa r tmen to f Neu ro logy , Un ive rs i tyo fA labamaa t B i rm ingham ,B i rm ingham ,AL ,USA Co r respondenceto :D r . Reza Bavasa rdshah r ipou r , Te l : 1 -205 -201 -4269 ,E -ma i l :nbava r@yahoo .com DO I :10 .1007 /s11655 -014 -1687 -8
Ch inJIn teg r Med
•2•
Inc lus ionC r i te r ia Werec ru i tedpa t ien tsagedbe tween55and90 yea rso ld w i thacu teischem ics t rokeinthe m idd le , an te r io r ,o rpos te r io rce reb ra la r te r iesand Na t iona l Ins t i tu teo f Hea l th S t roke Sca le(N IHSS )sco reo f a tleas t5 , who we readm i t teda t Go les tan Hosp i ta l , Ka ram i Hosp i ta l ,o r Emam Hosp i ta l(a l linI ran ) be tweenFeb rua ry2010toJune2010andcon f i rmed b yneu ro imag ing[e i the rcompu tedtomog raph y(CT )o r magne t i cre sonan ceimag ing(MR I ) ]w i th inonewee ko f random i za t ion . On l ythenewle s ion s we recon s ide red toberespons ib lefo rtheindexs t rokea tthet imeo f e l ig ib i l i t ya sseenontheba se l ine imag ing(CTo r MR I ) .
Exc lus ionC r i te r ia Weexc ludedpa t ien ts who we readm i t tedto thein tens iveca reun i t(astheya re mo rep roneto comp l ica t ions ) ,hadin t race reb ra lhaemo r rhageo r haemo r rhag icconve rs ion ,hadh is to ryo fp rev ious s t rokeo rev idenceo fp re -ex is t ings t rokeonb ra in imag ing ,hads ign i fican tsys tem icd isease ,i .e .ch ron ic obs t ruc t ive pu lmona ry d isease(COPD ) ,seve re a s thma ,CO2 na r co s i s ,rena lfa i lu re ,se ve reconge s t i ve hea r tfa i lu re ,u raem ia ,c i r rhos is , psychos is , demen t ia ,andb ra inpa tho log ieso the rthans t roke (e .g .p r ima ryb ra intumou rs , me tas tas iso rin fec t ious les ions ) ,andhadpa r t ic ipa tedinano the rc l in ica lt r ia l w i th in3 mon thso finc lus ion .
One to -onet rea tmen ta l loca t ion waspe r fo rmed acco rd ingtoacompu te r -gene ra tedrandom iza t ion l is tp repa reda tthes ta r to fthes tudy ,kep tind iv idua l ly sea led by an appo in teds tudys ta f f , andopened uponiden t i f ica t iono fane l ig ib lepa t ien t .A l lpa t ien ts rece iveds tanda rdt rea tmen tfo rs t roke ,inc lud ingan t i th rombo t i cthe rap y ,s ta t in ,b loodp re s su recon t ro l ,an t i d iabe t ic med ica t ions ,ando the rt rea tmen tsdeemed med ica l lynecessa ry .
Obse rva t ionI tems Base l inein fo rma t ioninc lud ingage ,gende r , race ,h is to ryo fhype r tens ion ,d iabe tes me l l i tus ,o r hype r l ip idem ia ,N IHSS ,ce reb ra la r te ryinvo lved , T r ia lo fO rganon10172in Acu te S t roke T rea tmen t (TOAST )c lass i fica t ion ,andlabo ra to rytes tsresu l tsfo r haemog lob in ,b loodu rean i t rogen(BUN ) ,c rea t in ine , sod ium ,po tass ium ,a lan inet rans fe rase(ALT ) ,and aspa r ta team ino t rans fe rase(AST ) we reco l lec ted . N IHSS and mod i f ied Rank in Sca le(mRS ) we re pe r formeda t3 mon ths(a tcomp le t iono ft rea tmen t ) . Pa t ien ts we re mon i to redfo r6 mon thsandda taon b loodp re s su re ,haemog lob in ,BUN ,c rea t in ine ,sod ium , po tass ium ,as we l lasoccu r renceo fadve rseeven ts , we reco l lec teda t1 ,3 ,and6 mon ths(3 mon thsa f te r comp le t iono ft rea tmen t ) .
In fo rmedconsen ts we re ob ta inedf rom a l l pa r t i c ipan t sa sapp ro vedb ythee th i c scomm i t teeo fthe Jound i shapou r Med i ca l Un i ve r s i t y wh i chi sre spon s ib le fo rtheth reeho sp i ta l s in vo l ved inth i ss tud y .
Thefo l low ingno rma lrange swe reu sedtoa s se s s whe the rb loodpa rame te rva lues we reabno rma l : meana r te r ia lb loodp re s su re(MABP )60–110 mm Hg , haemog lob in12–7g /dL , BUN8–25 mg /dL ,c rea t in ine 0 .6–1 .5 mg /dL ,sod ium135–145 mEq /L ,po tass ium 3 .5–5 .5 mEg /L ,ALT7–56U /L ,andAST5–40U /L .
In te rven t ions
S ta t is t ica lAna lys is
E l ig ib lepa t ien t swe rerandom l ya l lo ca tedtoe i the r re ce i v ingNeu roA iDo rp la ceboa sanadd -ont rea tmen t w i th inthef i rs t weeka f te rthes t rokea tadoseo f4 capsu les3t imesadayfo r3 mon ths . Pa t ien ts who requ i redtubefeed ing we reg i venthes tud yt rea tmen t b yopen ingthecap su le sandadm in i s te r ingthed i lu ted powde rcon ten t sth roughthetube .
Summa ry da ta we rerepo r ted as numbe rs andp ropo r t ionsfo rca tego r ica lva r iab lesandas mean±s tanda rddev ia t ionsfo rcon t inuousva r iab les . Wheneve rapp rop r ia te ,compa r isonsbe tweeng roups we repe r fo rmedus ingch i -squa retes t(o rF ishe r 's exac ttes tincaseso fce l lshav inglessthanthe expec tednumbe ro fobse rva t ions )fo rca tego r ica l va r iab les , andt tes t(o r ANOVAfo rrepea ted measu res )fo rcon t inuousva r iab letocompu tefo r s ta t is t ica ls ign ificance . AP va luelessthan0 .05 was cons ide reds ign ifican td i f fe rence .
Neu roA iDand ma tch ingp lacebo wassupp l ied bythe Go les tan Hosp i ta lpha rmacyasfundedby the un ive rs i ty . Neu roA iD was manu fac tu red by Mo leac(S ingapo re ) whe reeachba tcho fthep roduc t unde rwen tin -p rocessandf in ishedp roduc tqua l i ty con t ro lfo rbo thsa fe tyande f ficacyus ings tanda rd ized assays .
RESULTS Pa t ien tsInc lus ionandBase l ineCha rac te r is t ics N ine ty f ivepa t ien ts we reiden t i f iedfo reach
Ch inJIn teg r Med
•3•
Pa t ien tsw i thacu teischem ics t roke w i th in1weeko fonse t(190cases )
A l lo ca tedtoNeu roA iD(95ca se s )
A l loca tedtop lacebo(95cases )
Ba se l inec l in i ca land labo ra to r yda ta no tdonefo rva r iedrea son s(2ca se s )
Ba se l inec l in i ca land labo ra to r yda ta no tdone fo rva r iedrea son s(16ca se s )
Pa t ien t ss ta r tedonNeu roA iDand hadba se l ineda ta(93ca se s )
Pa t ien t ss ta r tedonp la ceboand hadba se l ineda ta(79ca se s )
D iedf roms t roke(hem ia t ion ) w i th in2weeks(3cases )
D iedf roms t roke(hem ia t ion ) w i th in2weeks(3cases )
Non -comp l ian tandlos tto fo l lowup(10cases )
Non -comp l ian tandlos tto fo l lowup(6cases )
Pa t ien tsonNeu roA iDandab le tofo l lowup(80cases )
Pa t ien tsonp laceboandab le tofo l lowup(70cases )
Pa t ien t scomp l ian tw i thNeu roA iD fo r3 mon th sandfo l lowedupa t 1 mon th ,3 mon th s ,and 6 mon th s(80ca se s )
Pa t ien t scomp l ian tw i thp la cebo fo r3 mon th sandfo l lowedupa t 1 mon th ,3 mon th s ,and 6 mon th s(70ca se s )
F igu re2 . S tudyF lowcha r t
t rea tmen ta rm ,bu t18pa t ien ts(2inthe Neu roA iD g roupand16inthep lacebog roup ) we reunab le tocomp ly w i thbase l inerequ i remen tsfo rc l in ica l andlabo ra to ryda tafo rva r iedreasons ,inc lud ing unava i lab i l i tyo fin fo rma t ionf romre fe r r inghosp i ta l , pa t ien tre fusa l ,and m issedp rocedu resbynon -s tudy s ta f f .N ine ty th reepa t ien tshadbase l ineda taand we res ta r tedonNeu roA iDand79pa t ien t sonp la cebo . Th reepa t ien tsineachg roupd ied w i th in2 weekso f s t rokeonse t .Thesedea ths we redeemedtobedue
totheunde r ly ingseve res t rokeandresu l t ingce reb ra l he rn ia t ion . Amongtherema in ingpa t ien ts ,16had poo rfo l low -upcomp l ianceandda tawe reava i lab lefo r ana lys isin150pa t ien ts(80pa t ien tsonNeu roA iDand 70pa t ien t sonp la cebo ) .Amongthe se150pa t ien t s ,a l l we recomp l ian ttothea l loca tedt rea tmen t ,noned ied , anda l lwe reab letofo l lowupfo rthe1 ,3and6 -mon th s a s se s smen t s(F igu re1 ) .A l lpa t ien t swe reCau ca s ian s . Base l inecha rac te r is t ics we res im i la rbe tweenthetwo g roups(Tab le1 ) .
Tab le1 . Base l ineCha rac te r is t icso fCoho r t I tem
Neu roA idg roup(80cases )
–
P lacebog roup(70cases )
P-va lue
r ) Age(x±s,yea
76 .7±8 .7
75 .9±7 .8
ns
Fema legende r(Case ,% )
38(48 )
30(43 )
ns
R iskfac to r(Case ,% ) Hype r tens ion
53(66 )
51(73 )
ns
D iabe tes me l l i tus
39(49 )
29(41 )
ns
Hype r l ip idem ia
40(50 )
30(43 )
ns
16 .3±3 .5
16 .6±3 .8
ns ns
– ±s,sco re ) N IHSS(x
Ce reb ra la r te rya f fec ted(Case ,% ) M idd lece reb ra la r te ry
40(50 )
33(47 )
An te r io rce reb ra la r te ry
20(25 )
15(22 )
Pos te r io rce reb ra la r te ry
20(25 )
22(31 )
61(76 )
52(74 )
9(11 )
12(17 )
10(12 )
6(9 )
TOASTc lass ifica t ion(Case ,% ) La rgevesse ld isease Ca rd ioembo l ism Sma l lvesse ld isease No te :ns ,no ts ta t is t ica l lys ign ifican td i f fe rence
ns
0 .87
0
3
25 .3±6 .1
0
0 .4 ±6 .5
24 .0±5 .7
0
0 .1 ±0 .5
4 .4±0 .4
0
–1 .0±5 .5
25 .4±5 .9
0
–0 .6±6 .1
24 .2±5 .6
0
–0 .0±0 .6
4 .4±0 .5
16
–0 .8±5 .3
140 .2±3 .9
0 .95
0 .86
0 .89
0 .95
0 .31
0 .81
0 .95
0 .31
0 .42
0 .83
0 .88
0 .99
0 .95
0 .52
0 .19
0 .67
