ARTICLES|?VOLUME16,ISSUE10,?P781-788,?OCTOBER01,2017Tenecteplase
versusalteplaseformanagementofacuteischaemicstrokeSummaryB
ackgroundTenecteplaseisanewerthrombolyticagentwithsomeph
armacologicaladvantagesoveralteplase.Previousphase2trials
oftenecteplaseinacuteischaemicstrokehaveshownpromisingre
sults.Weaimedtoinvestigatethesafetyandefficacyoftenecte
plaseversusalteplaseinpatientswithacutestrokewhowereeli
gibleforintravenousthrombolysis.MethodsThisphase3,randomise
d,open-label,blindedendpoint,superioritytrialwasdonein13
strokeunitsinNorway.Weenrolledadultswithsuspectedacute
ischaemicstrokewhowereeligibleforthrombolysisandadmitted
within4·5hofsymptomonsetorwithin4·5hofawakeningwiths
ymptoms,orwhowereeligibleforbridgingtherapybeforethrombe
ctomy.Patientswererandomlyassigned(1:1)toreceiveintraveno
ustenecteplase0·4mg/kg(toamaximumof40mg)oralteplase0·
9mg/kg(toamaximumof90mg),viaablockrandomisationschedu
lestratifiedbycentreofinclusion.Patientswerenotinformed
oftreatmentallocation;treatingphysicianswereawareoftreatm
entallocationbutthoseassessingtheprimaryandsecondaryendp
ointswerenot.Theprimaryoutcomewasexcellentfunctionaloutc
omedefinedasmodifiedRankinScale(mRS)score0–1at3months.
Theprimaryanalysiswasanunadjustedandnon-stratifiedintent
ion-to-treatanalysiswithlastobservationcarriedforwardfori
mputationofmissingdata.Thisstudyisregisteredwith?Clinical
Trials.gov,number?NCT01949948.FindingsBetweenSept1,2012,and
Sept30,2016,1107patientsmettheinclusioncriteriaandseven
patientswereexcludedbecauseinformedconsentwaswithdrawnor
eligibilityforthrombolytictreatmentwasreconsidered.1100pa
tientswererandomlyassignedtothetenecteplase(n=549)oralte
plase(n=551)groups.Themedianageofparticipantswas77years
(IQR64–79)andthemedianNationalInstitutesofHealthStroke
Scalescoreatbaselinewas4points(IQR2–8).Afinaldiagnosis
otherthanischaemicstrokeortransientischaemicattackwasfo
undin99(18%)patientsinthetenecteplasegroupand91(17%)p
atientsinthealteplasegroup.Theprimaryoutcomewasachieved
by354(64%)patientsinthetenecteplasegroupand345(63%)pat
ientsinthealteplasegroup(oddsratio1·08,95%CI0·84–1·38;
p=0·52).By3months,29(5%)patientshaddiedinthetenectepla
segroupcomparedwith26(5%)inthealteplasegroup.Thefreque
ncyofseriousadverseeventswassimilarbetweengroups(145[26
%]inthetenecteplasegroup?vs?141[26%]inthealteplasegroup;
p=0·74).InterpretationTenecteplasewasnotsuperiortoalteplase
andshowedasimilarsafetyprofile.Mostpatientsenrolledint
hisstudyhadmildstroke.Furthertrialsareneededtoestablish
thesafetyandefficacyinpatientswithseverestrokeandwheth
ertenecteplaseisnon-inferiortoalteplase.FundingResearchCoun
cilofNorway.ReferencesLeesKR?.BluhmkiE?.vonKummerR?.etal.
Timetotreatmentwithintravenousalteplaseandoutcomeinstrok
e:anupdatedpooledanalysisofECASS,ATLANTIS,NINDS,andEPIT
HETtrials.Lancet.?2010;?375:?1695-1703ViewinArticle?.Scopus(
1356).PubMed.Summary.FullText.FullTextPDF.GoogleScholar2.Bhat
iaR?.HillMD?.ShobhaN?.etal.Lowratesofacuterecanalization
withintravenousrecombinanttissueplasminogenactivatorinisc
hemicstroke:real-worldexperienceandacallforaction.Stroke
.?2010;?41:?2254-2258ViewinArticle?.Scopus(397).PubMed.Crossre
f.GoogleScholar3.WhiteleyWN?.EmbersonJ?.LeesKR?.etal.Risko
fintracerebralhaemorrhagewithalteplaseafteracuteischaemic
stroke:asecondaryanalysisofanindividualpatientdatameta-a
nalysis.LancetNeurol.?2016;?15:?925-933ViewinArticle?.Scopus
(58).PubMed.Summary.FullText.FullTextPDF.GoogleScholar4.Logal
loN?.KvistadCE?.ThomassenL?Therapeuticpotentialoftenectepl
aseinthemanagementofacuteischemicstroke.CNSDrugs.?2015;?
29:?811-818ViewinArticle?.Scopus(7).PubMed.Crossref.GoogleSch
olar5.BenedictCR?.RefinoCJ?.KeytBA?.etal.Newvariantofhuma
ntissueplasminogenactivator(TPA)withenhancedefficacyandl
owerincidenceofbleedingcomparedwithrecombinanthumanTPA.C
irculation.?1995;?92:?3032-3040ViewinArticle?.Scopus(124).PubM
ed.Crossref.GoogleScholar6.VanDeWerfF?.AdgeyJ?.ArdissinoD?.
etal.fortheAssessmentoftheSafetyandEfficacyofaNewThr
ombolytic(ASSENT-2)InvestigatorsSingle-bolustenecteplasecomp
aredwithfront-loadedalteplaseinacutemyocardialinfarction:
theASSENT-2double-blindrandomisedtrial.Lancet.?1999;?354:?71
6-722ViewinArticle?.Scopus(697).PubMed.Summary.FullText.Full
TextPDF.GoogleScholar7.ParsonsM?.SprattN?.BivardA?.etal.A
randomizedtrialoftenecteplaseversusalteplaseforacuteische
micstroke.NEnglJMed.?2012;?366:?1099-1107ViewinArticle?.Sc
opus(300).PubMed.Crossref.GoogleScholar8.HuangX?.CheripelliBK
?.LloydSM?.etal.Alteplaseversustenecteplaseforthrombolysis
afterischaemicstroke(ATTEST):aphase2,randomised,open-lab
el,blindedendpointstudy.LancetNeurol.?2015;?14:?368-376View
inArticle?.Scopus(86).PubMed.Summary.FullText.FullTextPDF.Go
ogleScholar9.IndredavikB?.SalvesenR?.NaessH?.Nasjonalretnin
gslinjeforbehandlingogrehabiliteringvedhjerneslag.?Helsedir
ektoratet,?Oslo2010:?1-196ViewinArticle?.GoogleScholar10.Europ
eanStrokeOrganisationExecutiveCommitee.ESOWritingCommittee
Guidelinesformanagementofischaemicstrokeandtransientisc
haemicattack2008.CerebrovascDis.?2008;?25:?457-507ViewinArt
icle?.Scopus(1842).PubMed.Crossref.GoogleScholar11.ThomallaG?.
ChengB?.EbingerM?.etal.DWI-FLAIRmismatchfortheidentificat
ionofpatientswithacuteischaemicstrokewithin4.5hofsympt
omonset(PRE-FLAIR):amulticentreobservationalstudy.LancetN
eurol.?2011;?10:?978-986ViewinArticle?.Scopus(250).PubMed.Summ
ary.FullText.FullTextPDF.GoogleScholar12.LogalloN?.KvistadC
E?.NacuA?.etal.TheNorwegiantenecteplasestroketrial(NOR-TE
ST):randomisedcontrolledtrialoftenecteplasevs.alteplasein
acuteischaemicstroke.BMCNeurol.?2014;?14:?106ViewinArticle
?.Scopus(28).PubMed.Crossref.GoogleScholar13.HackeW?.KasteM?.
FieschiC?.etal.Intravenousthrombolysiswithrecombinanttissu
eplasminogenactivatorforacutehemisphericstroke.TheEuropea
nCooperativeAcuteStrokeStudy(ECASS).JAMA.?1995;?274:?1017-1
025ViewinArticle?Scopus(2610).PubMed.Crossref.GoogleScholar1
4.HackeW?.KasteM?.BluhmkiE?.etal.Thrombolysiswithalteplase
3to4.5hoursafteracuteischemicstroke.NEnglJMed.?2008;?
359:?1317-1329ViewinArticle?.Scopus(3886).PubMed.Crossref.Goog
leScholar15.HackeW?.DonnanG?.FieschiC?.etal.Associationof
outcomewithearlystroketreatment:pooledanalysisofATLANTIS,
ECASS,andNINDSrt-PAstroketrials.Lancet.?2004;?363:?768-774
ViewinArticle?.Scopus(1932).PubMed.Summary.FullText.FullText
PDF.GoogleScholar16.WahlgrenN?.AhmedN?.DavalosA?.etal.Thro
mbolysiswithalteplaseforacuteischaemicstrokeintheSafeIm
plementationofThrombolysisinStroke-MonitoringStudy(SITS-MOS
T):anobservationalstudy.Lancet.?2007;?369:?275-282ViewinArt
icle?.Scopus(1418).PubMed.Summary.FullText.FullTextPDF.Google
Scholar17.AhmedN?.WahlgrenN?.GrondM?.etal.Implementationan
doutcomeofthrombolysiswithalteplase3-4.5hafteranacutes
troke:anupdatedanalysisfromSITS-ISTR.LancetNeurol.?2010;?9
:?866-874ViewinArticle?Scopus(201).PubMed.Summary.Full.TextFu
llTextPDF.GoogleScholar18.BathPM?.LeesKR?.SchellingerPD?.et
al.Statisticalanalysisoftheprimaryoutcomeinacutestroke
trials.Stroke.?2012;?43:?1171-1178ViewinArticle?.Scopus(141).
PubMed.Crossref.GoogleScholar19.NacuA?.KvistadCE?.NaessH?.et
al.NOR-SASS(NorwegianSonothrombolysisinAcuteStrokeStudy):
randomizedcontrolledcontrast-enhancedsonothrombolysisinanun
selectedacuteischemicstrokepopulation.Stroke.?2017;?48:?335-
341ViewinArticle?.Scopus(17).PubMed.Crossref.GoogleScholar20.
HaleyJr,EC?.ThompsonJL?.GrottaJC?.etal.PhaseIIB/IIItrial
oftenecteplaseinacuteischemicstroke:resultsofaprematurel
yterminatedrandomizedclinicaltrial.Stroke.?2010;?41:?707-711
ViewinArticle?.Scopus(119).PubMed.Crossref.GoogleScholar21.Ha
leyJr,EC?.LydenPD?.JohnstonKC?.HemmenTM?.TNKinStrokeInves
tigatorsApilotdose-escalationsafetystudyoftenecteplasein
acuteischemicstroke.Stroke.?2005;?36:?607-612ViewinArticle?.
Scopus(144).PubMed.Crossref.GoogleScholar22.MolinaCA?.RiboM?.
RubieraM?.etal.TNKinducesfasterMCArecanalizationandleads
tobettershort-andlong-termclinicaloutcomethannativetPA.
TheTNK-TPAreperfusionstrokestudy.Stroke.?2008;?39?(abstr).:
?563ViewinArticle?.GoogleScholar23.TanswellP?.ModiN?.CombsD
?.DanaysT?Pharmacokineticsandpharmacodynamicsoftenecteplase
infibrinolytictherapyofacutemyocardialinfarction.ClinPha
rmacokinet.?2002;?41:?1229-1245ViewinArticle?Scopus(85).PubMe
d.Crossref.GoogleScholar24.CannonCP?.GibsonCM?.McCabeCH?.etal.TNK-tissueplasminogenactivatorcomparedwithfront-loadedalteplaseinacutemyocardialinfarction:resultsoftheTIMI10Btrial.ThrombolysisinMyocardialInfarction(TIMI)10BInvestigators.Circulation.?1998;?98:?2805-2814ViewinArticle?Scopus(305).PubMed.Crossref.GoogleScholar25.VandeWerfF?.CannonCP?.LuytenA?.etal.Safetyassessmentofsingle-bolusadministrationofTNKtissue-plasminogenactivatorinacutemyocardialinfarction:theASSENT-1trial.TheASSENT-1Investigators.AmHeartJ.?1999;?137:?786-791ViewinArticle?.Scopus(151).PubMed.Summary.FullText.FullTextPDF.GoogleScholar |
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