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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-ACaseStudyofEn

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

stry,threestudiesChinahasbeenparticipatingin2.MoreinformationonE-five,FWH’sperformanceinE-five3.MoreinformationonPROTECT,FWH’sperformanceinPROTECT(A

PnewslettersnapshotandGlobalnewslettersnapshotreflectingrecognitiononFWH’sperformance)4.SummarizewhatFWHhasdonerightintheaboveglobaltrialstoesta

blishagoodreputationonclinicalstudy5.IntroducingChinaEndeavorRegistry(CER),usewhatFWHhasdonerightinE-fiveandPROTECTtoencouragesitesparticipat

inginCERtospeeduppatientenrollmentwhileensuringdataqualityRandomizedClinicalStudyOrganizationAnatomyStudyManagementTeamStudySitesSponsorCRAs*/Moni

torsRandomizationSystemDataManagement&StatisticalAnalysisCoreLabsCEC*CRA:ClinicalResearchAssociateCEC:ClinicalEventCommitteeClinicalS

tudyProcessPrestudypreparationSiteInitiationTrainingPatientEnrollmentStudyCloseoutSolveDataQueriesGenerateStud

yReport&PublicationPICRandomizationProcedureandFollow-upCRFDataEntryENDEAVORClinicalProgramUpdatePhaseIFIM48monthresultsDouble-blindRandomizedTrial

36monthresultsContinuedAccessSafety24monthresultsConfirmatoryTrialvs.Cypher24monthresultsConfirmatoryTrialvs.TaxusEnrollmentcompletedSingleArmTrial

30daysresultsReal-WorldPerformanceandSafetyEvaluation–EnrollmentcompletedEndeavorvs.CypherSafetyStudyEnrollingENDEAVORI(1

00patients)ENDEAVORII(1200patients)ENDEAVORIICARegistry(300patients)ENDEAVORIII(436patients)ENDEAVOR

IV(1548patients)ENDEAVORJapan(99patients)E-FiveRegistry(8000patients)PROTECT(8800patients)ChinaEndeavorRegistry(2200patients)Real-WorldPerfor

manceandSafetyEvaluation–EnrollingPhaseIFIM48monthresultsDouble-blindRandomizedTrial36monthresultsContinue

dAccessSafety24monthresultsConfirmatoryTrialvs.Cypher24monthresultsConfirmatoryTrialvs.Taxus12monthresultsSingleArmTrial9monthresultsRe

al-WorldPerformanceandSafetyEvaluation–EnrollmentcompletedEndeavorvs.CypherSafetyStudyEnrollingReal-WorldPerformanceandSafetyEvaluatio

n–EnrollingProspective,MulticenterRegistryAssessingSafetyinaRealWorldPatientPopulationE-FiveRegistryPrimaryEndpoint:MACEat12monthsSecondaryEn

dpoints:MACEat30daysand6mo,Stentthrombosis,proceduresuccessrate;devicesuccessrate;lesionsuccessrateDrugTh

erapy:ASAandClopidogrel>3monthsZotarolimusDose:10gpermmstentlengthSingleandMultipleCoronaryArteryLesionsStentDiamet

ers:2.25-4.0mmStentLength:8/9-30mmN=8,000patients200sitesEurope,AsiaPacific,Israel,SouthAmericaClinical/MACE30d6mo2yr*12mo*Limitednumb

erofcentersandspecificpatientsubset.E-fiveStudyOrganizationAnatomyMedtronicClinicalDepartmentStudySitesSponsorMedtronicCRAs/MonitorsE-CRF

SystemDataManagement&StatisticalAnalysisCoreLabsCECE-FiveRegistry(Recent)MI(%)NonQ-waveMIQwaveMIPriorC

ABG(%)UnstableAngina(%)DiabetesMellitus(%)PriorPCI(%)PriorMI(%)Age(years)MaleGender(%)n=8318PatientsPatientDemog

raphicsoftotalregistry76.763.30±11.0632.112.221.425.37.532.721.834.0E-FiveRegistryn=8318patientsand10343lesionsLAD(%)46.6B2/CLesions(%)60.3RVD(mm)2.9

3±0.47LesionLength(mm)18.50±10.60Pre-procedureMLD(mm)0.50±0.41Pre-procedureDS(%)82.84±13.51Post-procedureDS(

%)2.41±8.24BaselineAngiographyoftotalregistry(visualmeasurement)E-FiveRegistry21.2(Recent)MI(%)12.2NonQ-waveMI25.3QwaveMI7.0PriorCABG(%)31.2U

nstableAngina(%)34.4DiabetesMellitus(%)23.9PriorPCI(%)35.9PriorMI(%)62.95±11.46Age(years)76.9MaleGender(%)n=1989patientsPatientDemographics1989patie

ntsE-FiveRegistryn=1989patientsand2449lesionsLAD(%)47.9B2/CLesions(%)61.7RVD(mm)2.93±0.45LesionLength(m

m)18.19±9.90Pre-procedureMLD(mm)0.53±0.41Pre-procedureDS(%)81.93±13.99Post-procedureDS(%)2.01±6.33Ba

selineAngiographyof1989patients(visualmeasurement)18.19±9.90LesionLength(mm)1.35±0.53Stent:LesionLength28.8Longlesions(>20mm)(%)5.921.016.2

34.718.04.2MinimumEndeavorStentDiametersimplanted2.25mm(%)2.5mm(%)2.75mm(%)3.0mm(%)3.5mm(%)4.0mm(%)23.17±11.93TotalStentLength(mm)n=1989patient

sand2449lesionsE-FiveRegistryProcedureCharacteristicsof1989patientsE-FiveRegistryClinicalOutcomesDefinition•MACEisdef

inedasdeath,MI(Qwaveandnon-Qwave),emergentcardiacbypasssurgery,ortargetlesionrevascularization(repeatPTCAorCABG)

.•TLRisdefinedasanyclinicallydrivenrepeatpercutaneousinterventionofthetargetlesionorbypasssurgeryofthetargetvessel.•TVF

isdefinedastargetvesselrevascularization(definedbelow),recurrentQorNonQ-Wavemyocardialinfarction,orcardiacdeaththatcouldnotbeclearlya

ttributedtoavesselotherthanthetargetvessel.Targetvesselfailurewillbereportedwhen:1.RecurrentMIoccursinterritorynotclearlyotherthantha

tofthetargetvessel.2.Cardiacdeathnotclearlyduetoanon-targetvesselendpoint.3.Targetvesselrevascularizationisdetermined.E-FiveRegistry30daysn=

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(c

ardiac)+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)31-360day

s00.2(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)C

linicalOutcomesoutto12monthsE-FiveRegistryComplexSubsetsSamplesizen=1989Diabetics-%(n)InsulinDependent-%(n)NonInsulinDependen

t–%(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)•MyocardialInfarctionupto72hourspriortothePCIandstentingprocedur

e•**Lesioninvolvingmainandsidebranch,requiring+2EndeavorstentsE-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(car

diac)+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(n

on-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)DiabeticsClinicalOutcomesoutto12mo

nthsE-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)StentThrombosis(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-FiveRegistry30daysn=91312monthsn=866Dea

th(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(card

iac)+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(83)TVF-%(n)2.0(18)9.2(80)RVD<2.75mmClinicalOut

comesoutto12monthsE-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)QWave

0.2(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)Sten

tThrombosis(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)StentThrombos

is(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-Fiveregistryenrolledpatientstha

trepresentthe“realworld”ofPCI–Therehavebeenindependenteventadjudication,performing10%monitoringtodetectunderreportingofevents–Thefirst2000patie

ntshasprovidedinsightintothesafetyandefficacyoftheEndeavorDESinamorecomplexpatientpopulation•Conclusions:–TheEndeav

orDrugElutingStentwasassociatedwithalowMACEandTLRinthefirst1989patientsstudiedoutto12months–Despitetherelativecomplexityofthispati

entcohortthesafetyoutcomes–cardiacdeath,MIandstentthrombosiswerealsolow–TheseresultsareconsistentwiththeoutcomesreportedwiththeEndeavorDESintrialse

nrollingmoremoderatelesionsandpatientsConclusionFuWaiHospitalinE-Five•Thebestperformerinpatientenrollmentbasedonaveragepa

tientrecruitedperweek:13+patientsperweek•Excellentcompliance–Completesourcedocumentavailable–Follow-upstrictlywithinprotocoltimeframe–AEreportingfoll

owingapplicablerequirements•Selectedsiteswereinvitedforanextendedtwo-yearfollow-upbasedonpatientenrollmentspe

edandstudyquality,FWHisoneoftheonlythreehospitalsinAsiaPacificreceivedtheinvitationPROTECT-STUDYDESIGNProspective,multi-center,randomized,two-arm

,open-labeltrialPatients:SingleandMultipleCoronaryArteryLesionsCypherStentN=44008,800patients200sitesClinicalFUProcedure30d1yr2yrs3yrs4yrs5yrsAnti

-platelettherapyfor3–12monthsPrimaryendpointat3yearsPrimaryEndpoint:Overallstentthrombosisat3yearsdefinedasdefiniteandprobabl

eaccordingtotheARCdefinitioncriteriaMainSecondaryEndpoint:compositeendpointoftotaldeathorcardiacdeathcombinedwiththenumberofpatientswit

hallnon-fatalMIaswellasthenumberofpatientswithlargenon-fatalMIat3yearsAdditionalSecondaryEndpoints(at30Days,6Mo,1,1½,2,2½,3,4,5Yrs):TotalDea

thandsubcategoriesofDeathLargeandallMI,Stentthrombosisdefinedasdefinite,probableandpossible,Compositescoreofclinicaloutcomes(death,myo

cardialinfarction,strokeandrevascularization),MajorAdverseCardiacandCerebralEvents(MACCE)Stroke(hemorrhagicinnaturewhileonclopidogrel),Ble

edingcomplicationsingeneral,TLR,TVR,non-TVR,Proceduralsuccess,Devicesuccess,Lesionsuccess6mo1½yr2½yrEndeavorStentN=4400ASSUMPTIONSPRIMARYEN

DPOINT419631341.5%0.62.5%Power(1-)90%Power(1-)80%PatientsperarmENDEAVORHRCYPHERThestent-specificoutcomeofthrombosisoffer

sbestpowertodetectdifferencesbetweendifferentDESWith4196ptsperarm,thetrialispoweredtodetecta1%absolutereductio

ninstentthrombosisratesPROTECTSAMPLESIZECALCULATIONPrimaryendpoint:3yearFreedomfromstentthrombosis(ARCdefiniteandprobable)•Ho:lEn

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

ysesThecalculatedsamplesizeis4196patientsperarm;Atotalof8800patientswillbeenrolledaccountingfor<10%losttofollow-up.PR

OTECTStudyOrganizationAnatomyMedtronicClinicalDepartment&CROStudySitesSponsorMedtronicCRAs*/MonitorsRandomizationSystemE-CRFsystemDataManagement

&StatisticalAnalysisCoreLabsCRA:ClinicalResearchAssociateCEC:ClinicalEventCommitteeCEC*PROTECTGlobalUpdateWaitingforMedtro

nicEuropetosendmethelatestglobalnewsletterinwhichFuwaiwillberecognizedandthankedforitsstudyperformance.

Thisslidewillbeupdatedsoon…FuWaiHospitalinPROTECT•95patientsenrolledin15weeks•StudydataqualityrecognizedthroughtwostudycomplianceassessmentFWH’s

ClinicalResearchTeam•Cultivateresearchatmospherethroughcontinuousclinicalstudytrainingandparticipationinhighstandardc

linicaltrials•ClearlydefinerolesandresponsibilitiestoensureaccountabilityClinicalStudyCathLabDirectorCathLabOperatorsStudyCoordinatorappoin

tedfromthephysiciangroupTechniciansforQCACDmakingDedicatedStudyF/UTeamCathLabNursesforDataEntryTopQualityWorkWinsCredibilityinTrueG

lobalClinicalTrials•Ensurethatthewholeresearchteamreceivescomprehensivetrainingonanyspecificstudy•Dedicatedstudycoor

dinatorandclearlydefinedrolesandresponsibilitiestoenforceaccountability•Followingtheglobalstandardongoodclinicalpractice•

ImpressivepatientenrollmentpaceprovidedstudydataqualityisnotcompromisedProspective,MulticenterRegistryAssessin

gSafetyinaRealWorldChinesePatientPopulationChinaEndeavorRegistry(Endeavor-China)PrimaryEndpoint:MACEat12monthsSeco

ndaryEndpoints:MACEat30daysand6mo,Stentthrombosis,proceduresuccessrate;devicesuccessrate;lesionsuccessrateDrugTherapy:ASAandClopidogrel>3monthsZo

tarolimusDose:10gpermmstentlengthSingleandMultipleCoronaryArteryLesionsStentDiameters:2.25-4.0mmStentLength:8/9-30mmN=2,200patients32sitesacr

ossChinaClinical/MACE30d6mo2yr*12mo*Limitednumberofcentersandspecificpatientsubset.GoalsofEndeavorChinaRegistr

y•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‘realworl

d’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ToassesstheeventrateinChinesepatientsknow

ntohaveahigherriskofmajoradversecardiacevents,forexamplepatientswithdiabetesmellitus,smallvesselsandlonglesionsChinaEndeavorReg

istrySampleSizeCalculation•TheprimaryendpointistheMajorAdverseCardiacEvents(MACE)rateat1yearpost-pro

cedure.Thisendpointisdefinedasdeath,myocardialinfarction(Qwaveandnon-Qwave),emergentcardiacbypasssurgery,ortargetlesionrevascularization(repeatPTCAo

rCABG).•PreviousstudieshavesuggestedthattheMACErateatoneyearisapproximately11%.Underthisassumption,asamplesizeof2200willprovide95

%confidencethattherateofMACEat1yearwillnotexceed12.4%.•Thissamplesizeallowsfora10%rateoflosttofollow-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ChinaEndeavorRegistryStudyProcessPrestudypreparationSiteInitiationTrainingPatientE

nrollmentStudyCloseoutSolveDataQueriesGenerateStudyReport&PublicationPICProcedureandFollow-upCRFDataEntryChinaE

ndeavorRegistry•StudymanagementfollowingMedtronicUS/Europestandard•Monitoringofabout50%ofpatients•Datamanagementandstatisticalanalys

isoverseenbyMedtronicUS•Aimingfordatareleaseinmajorinternationalanddomesticconferences•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7HotTopics

onChinaEndeavorRegistry•PICunsigned•Delayeddataentry•Nodedicatedcoordinatoroverseeingthestudy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