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以高品质在真正的世界级临床试验中建立声誉：Endeavor在中国临床试验的案例分析TopQualityWorkWinsCredibilityinTrueGlobalClinicalTrials-ACaseStudyofEndeavor

ClinicalProgramsinChina阜外心血管病医院介入导管室徐波StoryFlow1.MedtronicglobalEndeavorclinicalprogramoverview,tohighlightE-five,PROTECT,China

EndeavorRegistry,threestudiesChinahasbeenparticipatingin2.MoreinformationonE-five,FWH’sperformanceinE-five3.MoreinformationonPROTECT,FWH’sperfo

rmanceinPROTECT(APnewslettersnapshotandGlobalnewslettersnapshotreflectingrecognitiononFWH’sperformance)4.Summariz

ewhatFWHhasdonerightintheaboveglobaltrialstoestablishagoodreputationonclinicalstudy5.IntroducingChinaE

ndeavorRegistry(CER),usewhatFWHhasdonerightinE-fiveandPROTECTtoencouragesitesparticipatinginCERtospeeduppatie

ntenrollmentwhileensuringdataqualityRandomizedClinicalStudyOrganizationAnatomyStudyManagementTeamStudySitesSponsorCRAs*/MonitorsRandomi

zationSystemDataManagement&StatisticalAnalysisCoreLabsCEC*CRA:ClinicalResearchAssociateCEC:ClinicalEventCommitteeClinicalStudyProcessPrestudyprepara

tionSiteInitiationTrainingPatientEnrollmentStudyCloseoutSolveDataQueriesGenerateStudyReport&PublicationPICRandomizationProcedureandFollow-upCRFDataEn

tryENDEAVORClinicalProgramUpdatePhaseIFIM48monthresultsDouble-blindRandomizedTrial36monthresultsContinued

AccessSafety24monthresultsConfirmatoryTrialvs.Cypher24monthresultsConfirmatoryTrialvs.TaxusEnrollmentcompletedSingleArmTrial30daysresultsReal-World

PerformanceandSafetyEvaluation–EnrollmentcompletedEndeavorvs.CypherSafetyStudyEnrollingENDEAVORI(100patients)ENDEAVORII

(1200patients)ENDEAVORIICARegistry(300patients)ENDEAVORIII(436patients)ENDEAVORIV(1548patients)ENDEAVORJapan(99patients)E-F

iveRegistry(8000patients)PROTECT(8800patients)ChinaEndeavorRegistry(2200patients)Real-WorldPerformanceandSafetyEvaluation–Enrolling

PhaseIFIM48monthresultsDouble-blindRandomizedTrial36monthresultsContinuedAccessSafety24monthresultsConfir

matoryTrialvs.Cypher24monthresultsConfirmatoryTrialvs.Taxus12monthresultsSingleArmTrial9monthresultsReal-WorldPerformanceandSafetyEvaluation–Enrol

lmentcompletedEndeavorvs.CypherSafetyStudyEnrollingReal-WorldPerformanceandSafetyEvaluation–EnrollingPros

pective,MulticenterRegistryAssessingSafetyinaRealWorldPatientPopulationE-FiveRegistryPrimaryEndpoint:MACEat12month

sSecondaryEndpoints:MACEat30daysand6mo,Stentthrombosis,proceduresuccessrate;devicesuccessrate;lesion

successrateDrugTherapy:ASAandClopidogrel>3monthsZotarolimusDose:10gpermmstentlengthSingleandMultipleCoronaryArteryLe

sionsStentDiameters:2.25-4.0mmStentLength:8/9-30mmN=8,000patients200sitesEurope,AsiaPacific,Israel,SouthAm

ericaClinical/MACE30d6mo2yr*12mo*Limitednumberofcentersandspecificpatientsubset.E-fiveStudyOrganizationAnatomyMedtronicClinicalDepartmentStudyS

itesSponsorMedtronicCRAs/MonitorsE-CRFSystemDataManagement&StatisticalAnalysisCoreLabsCECE-FiveRegistry(

Recent)MI(%)NonQ-waveMIQwaveMIPriorCABG(%)UnstableAngina(%)DiabetesMellitus(%)PriorPCI(%)PriorMI(%)Age(years)MaleGender(%)n=8318PatientsPatient

Demographicsoftotalregistry76.763.30±11.0632.112.221.425.37.532.721.834.0E-FiveRegistryn=8318patientsand10343lesionsLA

D(%)46.6B2/CLesions(%)60.3RVD(mm)2.93±0.47LesionLength(mm)18.50±10.60Pre-procedureMLD(mm)0.50±0.41Pre-procedureDS(%)82.84±13.51Post-pr

ocedureDS(%)2.41±8.24BaselineAngiographyoftotalregistry(visualmeasurement)E-FiveRegistry21.2(Recent)MI(%)12.2NonQ-wa

veMI25.3QwaveMI7.0PriorCABG(%)31.2UnstableAngina(%)34.4DiabetesMellitus(%)23.9PriorPCI(%)35.9PriorMI(%)62.95±11.46Age

(years)76.9MaleGender(%)n=1989patientsPatientDemographics1989patientsE-FiveRegistryn=1989patientsand2449lesionsLAD(%)47.9B2/CLesions(%)61.7RVD(m

m)2.93±0.45LesionLength(mm)18.19±9.90Pre-procedureMLD(mm)0.53±0.41Pre-procedureDS(%)81.93±13.99Post-procedureDS(%)2.01±6.33BaselineAngiographyof1989p

atients(visualmeasurement)18.19±9.90LesionLength(mm)1.35±0.53Stent:LesionLength28.8Longlesions(>20mm)(%)5.921.016.234.718.04.

2MinimumEndeavorStentDiametersimplanted2.25mm(%)2.5mm(%)2.75mm(%)3.0mm(%)3.5mm(%)4.0mm(%)23.17±11.93TotalStentLength(mm)n=1989p

atientsand2449lesionsE-FiveRegistryProcedureCharacteristicsof1989patientsE-FiveRegistryClinicalOutcomesDefinition•MACEisdefinedasdeath,

MI(Qwaveandnon-Qwave),emergentcardiacbypasssurgery,ortargetlesionrevascularization(repeatPTCAorCABG).•

TLRisdefinedasanyclinicallydrivenrepeatpercutaneousinterventionofthetargetlesionorbypasssurgeryofthetargetvessel.•T

VFisdefinedastargetvesselrevascularization(definedbelow),recurrentQorNonQ-Wavemyocardialinfarction,orcardiacdeathth

atcouldnotbeclearlyattributedtoavesselotherthanthetargetvessel.Targetvesselfailurewillbereportedwhen:1.RecurrentMIoccursinterritorynotcle

arlyotherthanthatofthetargetvessel.2.Cardiacdeathnotclearlyduetoanon-targetvesselendpoint.3.Targetvesselrevascularizationisdetermined.E-Fiv

eRegistry30daysn=198912monthsn=1989Death(all)-%(n)0.8(16)2.9(55)Cardiac0.7(14)2.0(38)MI(all)-%(n)0.8(15)1.3(25)QWave0.2(4)0.4(8)NonQwave0.6(11)0.9

(17)Death(cardiac)+MI(all)-%(n)1.4(27)3.0(57)StentThrombosis(all)-%(n)0.8(16)1.1(20)0-30days0.8(16)0.8(16)31-360days00.2(4)TLR-%

(n)0.5(10)3.8(71)TVR(non-TL)-%(n)0.1(1)1.1(20)TVR-%(n)0.5(10)4.6(87)MACE-%(n)1.7(33)7.0(133)TVF-%(n)1.6(31)6.8(129)ClinicalO

utcomesoutto12monthsE-FiveRegistryComplexSubsetsSamplesizen=1989Diabetics-%(n)InsulinDependent-%(n)NonInsulinDependent–%(n)34.4(684)9.2(182)25.2

(502)Lesions>20mm-%(n)34.4(685)RVD<2.75mm–%(n)46.1(916)RecentMI*-%(n)UnstableAngina-%(n)21.2(421)31.2(620)Bifurcations**-%(n)

19.3(384)•MyocardialInfarctionupto72hourspriortothePCIandstentingprocedure•**Lesioninvolvingmainandsidebranch,requiring+2Endeavorstent

sE-FiveRegistry30daysn=68212monthsn=649Death(all)-%(n)1.5(10)4.9(32)Cardiac1.2(8)3.5(23)MI(all)-%(n)1.0(7)1.7(11)QWave0.3(2)0.6(4)

NonQwave0.7(5)1.1(7)Death(cardiac)+MI(all)-%(n)1.9(13)4.5(29)StentThrombosis(all)-%(n)1.3(9)1.7(11)0-30days1.3(9)1.4(9)31-360days00.3(2)TLR-%(n)0

.9(6)4.8(31)TVR(non-TL)-%(n)0.1(1)0.9(6)TVR-%(n)0.9(6)5.5(36)MACE-%(n)2.3(16)9.6(62)TVF-%(n)2.1(14)8.

8(57)DiabeticsClinicalOutcomesoutto12monthsE-FiveRegistry30daysn=68212monthsn=649Death(all)-%(n)1.2(8)4.2(27)Cardiac0.%(6

)2.8(18)MI(all)-%(n)1.2(8)2.2(14)QWave0.1(1)0.6(4)NonQwave1.0(7)1.5(10)Death(cardiac)+MI(all)-%(n)2.1(14)4.5(29)StentThro

mbosis(all)-%(n)1.0(7)1.5(10)0-30days1.0(7)1.1(7)31-360days00.5(3)TLR-%(n)0.6(4)4.8(31)TVR(non-TL)-%(n)0.1(1)0.9(6)TVR-%(n)0

.6(4)5.4(35)MACE-%(n)2.6(18)9.7(63)TVF-%(n)2.3(16)8.8(57)Lesions>20mmClinicalOutcomesoutto12monthsE-FiveRegist

ry30daysn=91312monthsn=866Death(all)-%(n)1.1(10)3.5(30)Cardiac0.9(8)2.5(22)MI(all)-%(n)1.1(10)2.0(17)QWave0.2(

2)0.6(5)NonQwave0.9(8)1.4(12)Death(cardiac)+MI(all)-%(n)1.8(16)3.9(34)StentThrombosis(all)-%(n)1.1(10)1.5(13)0-30days1.1(10)

1.2(10)31-360days00.3(3)TLR-%(n)0.7(6)5.8(50)TVR(non-TL)-%(n)0.1(1)1.3(11)TVR-%(n)0.7(6)6.8(59)MACE-%(n)2.2(20)9.6(8

3)TVF-%(n)2.0(18)9.2(80)RVD<2.75mmClinicalOutcomesoutto12monthsE-FiveRegistry30daysn=61612monthsn=579Death(all)-%(n)1.0(6)2.6(15)Cardiac1.0(6)1

.7(10)MI(all)-%(n)0.6(4)0.9(5)QWave0.2(1)0.2(1)NonQwave0.5(3)0.7(4)Death(cardiac)+MI(all)-%(n)1.5(9)2.4(14)StentThrombosis(all)-%(n)0.8(5)1.2(7)0-

30days0.8(5)0.9(5)31-360days00.3(2)TLR-%(n)0.3(2)3.8(22)TVR(non-TL)-%(n)00.3(2)TVR-%(n)0.3(2)4.1(24)MACE-%(n)1.5(9)6.7(39)TVF-%(n)1.5(9)6.0(

35)UnstableAnginaClinicalOutcomesoutto12monthsE-FiveRegistry30daysn=42112monthsn=393Death(all)-%(n)2.1(9)5.3(

21)Cardiac1.7(7)4.3(17)MI(all)-%(n)1.2(5)2.5(10)QWave00.8(3)NonQwave1.2(5)1.8(7)Death(cardiac)+MI(all)-%(n)2.6(11)5.9(23)StentThrombosis(all)-%(n

)1.4(6)1.8(7)0-30days1.4(6)1.5(6)31-360days00.3(1)TLR-%(n)0.7(3)2.0(8)TVR(non-TL)-%(n)00.3(1)TVR-%(n)0.7(3)2.3(9)MACE-%(n)3.3(14)

7.9(31)TVF-%(n)2.9(12)7.1(28)RecentMIClinicalOutcomesoutto12monthsE-FiveRegistry30daysn=38412monthsn=359Death(all)-%(

n)1.0(4)4.2(15)Cardiac1.0(4)3.3(12)MI(all)-%(n)1.3(5)2.2(8)QWave0.3(1)0.3(1)NonQwave1.0(4)1.9(7)Death(cardiac)+MI(all)-%(n)2.1(8)4.5(16)

StentThrombosis(all)-%(n)1.3(5)1.7(6)0-30days1.3(5)1.4(5)31-360days00.3(1)TLR-%(n)0.5(2)4.7(17)TVR(non-TL)-%(n)01.9(7)TVR-%(n)

0.5(2)6.4(23)MACE-%(n)2.1(8)8.9(32)TVF-%(n)2.1(8)9.5(34)BifurcationlesionsClinicalOutcomesoutto12monthsE-FiveRegistry•InSummary:–

TheE-Fiveregistryenrolledpatientsthatrepresentthe“realworld”ofPCI–Therehavebeenindependenteventadjudication,performing10%monitori

ngtodetectunderreportingofevents–Thefirst2000patientshasprovidedinsightintothesafetyandefficacyoftheEndeavorDESinamorecomplexpatientpopulation•Conc

lusions:–TheEndeavorDrugElutingStentwasassociatedwithalowMACEandTLRinthefirst1989patientsstudiedoutto12months–Despitetherelativecomplexity

ofthispatientcohortthesafetyoutcomes–cardiacdeath,MIandstentthrombosiswerealsolow–TheseresultsareconsistentwiththeoutcomesreportedwiththeEndeavor

DESintrialsenrollingmoremoderatelesionsandpatientsConclusionFuWaiHospitalinE-Five•Thebestperformerinpatientenrollmentbasedonaveragepatientrecruite

dperweek:13+patientsperweek•Excellentcompliance–Completesourcedocumentavailable–Follow-upstrictlywithinp

rotocoltimeframe–AEreportingfollowingapplicablerequirements•Selectedsiteswereinvitedforanextendedtwo-yearfollow-upbasedonpa

tientenrollmentspeedandstudyquality,FWHisoneoftheonlythreehospitalsinAsiaPacificreceivedtheinvitationPROTECT-ST

UDYDESIGNProspective,multi-center,randomized,two-arm,open-labeltrialPatients:SingleandMultipleCoronaryArteryLesionsCy

pherStentN=44008,800patients200sitesClinicalFUProcedure30d1yr2yrs3yrs4yrs5yrsAnti-platelettherapyfor3–12monthsPrimaryendpointat3year

sPrimaryEndpoint:Overallstentthrombosisat3yearsdefinedasdefiniteandprobableaccordingtotheARCdefinitioncriteriaMainSecondaryEnd

point:compositeendpointoftotaldeathorcardiacdeathcombinedwiththenumberofpatientswithallnon-fatalMIaswellasthenumberofpatientswithlargenon-fatal

MIat3yearsAdditionalSecondaryEndpoints(at30Days,6Mo,1,1½,2,2½,3,4,5Yrs):TotalDeathandsubcategoriesofDeathLargeandallMI,Sten

tthrombosisdefinedasdefinite,probableandpossible,Compositescoreofclinicaloutcomes(death,myocardialinfarction,strokea

ndrevascularization),MajorAdverseCardiacandCerebralEvents(MACCE)Stroke(hemorrhagicinnaturewhileonclopidogrel),Bleedingcomplicationsin

general,TLR,TVR,non-TVR,Proceduralsuccess,Devicesuccess,Lesionsuccess6mo1½yr2½yrEndeavorStentN=4400A

SSUMPTIONSPRIMARYENDPOINT419631341.5%0.62.5%Power(1-)90%Power(1-)80%PatientsperarmENDEAVORHRCYPHERThestent-speci

ficoutcomeofthrombosisoffersbestpowertodetectdifferencesbetweendifferentDESWith4196ptsperarm,thetrialispoweredtodetecta1%absolutereductioni

nstentthrombosisratesPROTECTSAMPLESIZECALCULATIONPrimaryendpoint:3yearFreedomfromstentthrombosis(ARCdefiniteandprobable)•Ho:lEndeavo

r=lCypher•Ha:lEndeavor≠lCypherAssumptions•TreatmenteffecthazardratiolEndeavor/lCypher=0.6•Power:90%•Two-sidedalphaerror:5%•3interimanalysesThecalcu

latedsamplesizeis4196patientsperarm;Atotalof8800patientswillbeenrolledaccountingfor<10%losttofollow-up.PROTECTStudyOrganization

AnatomyMedtronicClinicalDepartment&CROStudySitesSponsorMedtronicCRAs*/MonitorsRandomizationSystemE-CRFsystemDataManagemen

t&StatisticalAnalysisCoreLabsCRA:ClinicalResearchAssociateCEC:ClinicalEventCommitteeCEC*PROTECTGlobalUpdateWaitingforMedtronicEuropetosendmet

helatestglobalnewsletterinwhichFuwaiwillberecognizedandthankedforitsstudyperformance.Thisslidewillbeupdat

edsoon…FuWaiHospitalinPROTECT•95patientsenrolledin15weeks•Studydataqualityrecognizedthroughtwostudycomplianc

eassessmentFWH’sClinicalResearchTeam•Cultivateresearchatmospherethroughcontinuousclinicalstudytrainingandparticipationinhighstan

dardclinicaltrials•ClearlydefinerolesandresponsibilitiestoensureaccountabilityClinicalStudyCathLabDirectorCathL

abOperatorsStudyCoordinatorappointedfromthephysiciangroupTechniciansforQCACDmakingDedicatedStudyF/UTeamCathLabNursesforDataEntryTopQualityWorkWinsCre

dibilityinTrueGlobalClinicalTrials•Ensurethatthewholeresearchteamreceivescomprehensivetrainingonanyspecificstudy•Dedicat

edstudycoordinatorandclearlydefinedrolesandresponsibilitiestoenforceaccountability•Followingtheglobalstandardongoodclinica

lpractice•ImpressivepatientenrollmentpaceprovidedstudydataqualityisnotcompromisedProspective,Multicen

terRegistryAssessingSafetyinaRealWorldChinesePatientPopulationChinaEndeavorRegistry(Endeavor-China)PrimaryEn

dpoint:MACEat12monthsSecondaryEndpoints:MACEat30daysand6mo,Stentthrombosis,proceduresuccessrate;devicesuccessrate;lesionsuccessrateDrugTherapy

:ASAandClopidogrel>3monthsZotarolimusDose:10gpermmstentlengthSingleandMultipleCoronaryArteryLesionsStentDiameters:2.25-4.0mmStentLength:8/9-3

0mmN=2,200patients32sitesacrossChinaClinical/MACE30d6mo2yr*12mo*Limitednumberofcentersandspecificpatientsubset.GoalsofEndeavorChi

naRegistry•通过入选“真实世界”中国病人以扩展对Endeavor支架的临床认识ToexpandtheclinicalknowledgebaseforEndeavorstentdeliverysystembyincluding‘realworld

’patientsinChina•评估在中国病人中对主要不良心脏事件高危患者临床事件的发生率，如糖尿病、小血管及长病变病人ToassesstheeventrateinChinesepatientsknowntohaveahigherriskofmajoradversecardiacevents,f

orexamplepatientswithdiabetesmellitus,smallvesselsandlonglesionsChinaEndeavorRegistrySampleSizeCalculation•TheprimaryendpointistheMajorAdverseC

ardiacEvents(MACE)rateat1yearpost-procedure.Thisendpointisdefinedasdeath,myocardialinfarction(Qwaveandnon-Qwave),emergentcardiacbypasssurg

ery,ortargetlesionrevascularization(repeatPTCAorCABG).•PreviousstudieshavesuggestedthattheMACErateatoneyearisapproximately11%.Underthisassumption,a

samplesizeof2200willprovide95%confidencethattherateofMACEat1yearwillnotexceed12.4%.•Thissamplesizeallowsfora10%rateoflo

sttofollow-up.ChinaEndeavorRegistry执行委员会(按姓氏字母顺序）陈纪言教授韩雅玲教授霍勇教授王伟民教授徐波主任临床事件仲裁委员会(按姓氏字母顺序）高润霖院士葛均波教授黄德嘉教授沈卫峰教授杨跃进教授ChinaEndeavorRegi

stryStudyProcessPrestudypreparationSiteInitiationTrainingPatientEnrollmentStudyCloseoutSolveDataQueriesGenerateStu

dyReport&PublicationPICProcedureandFollow-upCRFDataEntryChinaEndeavorRegistry•StudymanagementfollowingMedtronicUS/Europestandard•Monitoringofabout50

%ofpatients•DatamanagementandstatisticalanalysisoverseenbyMedtronicUS•Aimingfordatareleaseinmajorinternationalanddomesticconf

erences•Targetingonpublicationintoptierjournals研究进展StudyprogressbyMarch,2008•第一个病人入选：沈阳军总2007年11月FirstPat.In:Nov.2007bySYMilitary•入选720病人

,启动医院30家720patientsenrolledfrom30activatedhospitals•入选病人数最多,thetopenrollers：北京安贞医院96沈阳军总80（完成计划）北京朝阳医院50•

平均入选最快（/周),thefastestenroller(weekly)：广东省人民医院9北京安贞医院8沈阳军总7HotTopicsonChinaEndeavorRegistry•PICunsigned•Delayeddataentry•N

odedicatedcoordinatoroverseeingthestudy结语与同道共勉•“求乎上,得乎中;求乎中,得乎下;求乎下,无所得”只有在一开始就依照严格的临床试验标准来进行研究才能养成严谨的研究作风-以便在机会降临

时能够好好把握•在临床试验中遵从“又好又快”的游戏规则•用二十年建立起来的声誉可以在一个研究中毁于一旦;诚信为本,立足长远