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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,ChinaEndeavorRegistry,threestudiesChinahasbeenparticipatingin2.MoreinformationonE-five,FWH’sper

formanceinE-five3.MoreinformationonPROTECT,FWH’sperformanceinPROTECT(APnewslettersnapshotandGlobalnewsl

ettersnapshotreflectingrecognitiononFWH’sperformance)4.SummarizewhatFWHhasdonerightintheaboveglobaltrialstoest

ablishagoodreputationonclinicalstudy5.IntroducingChinaEndeavorRegistry(CER),usewhatFWHhasdonerightinE-fiveandPROTECTto

encouragesitesparticipatinginCERtospeeduppatientenrollmentwhileensuringdataqualityRandomizedClinicalSt

udyOrganizationAnatomyStudyManagementTeamStudySitesSponsorCRAs*/MonitorsRandomizationSystemDataManagement&St

atisticalAnalysisCoreLabsCEC*CRA:ClinicalResearchAssociateCEC:ClinicalEventCommitteeClinicalStudyProcessPrestud

ypreparationSiteInitiationTrainingPatientEnrollmentStudyCloseoutSolveDataQueriesGenerateStudyReport&PublicationPICRandomizationProcedurea

ndFollow-upCRFDataEntryENDEAVORClinicalProgramUpdatePhaseIFIM48monthresultsDouble-blindRandomizedTrial36monthresultsContinuedAccessS

afety24monthresultsConfirmatoryTrialvs.Cypher24monthresultsConfirmatoryTrialvs.TaxusEnrollmentcompletedSingleArmTrial30daysresultsReal-

WorldPerformanceandSafetyEvaluation–EnrollmentcompletedEndeavorvs.CypherSafetyStudyEnrollingENDEAVORI(100patients)ENDEAVORII(1200patients)ENDEAVORII

CARegistry(300patients)ENDEAVORIII(436patients)ENDEAVORIV(1548patients)ENDEAVORJapan(99patients)E-FiveRegistry(8000patie

nts)PROTECT(8800patients)ChinaEndeavorRegistry(2200patients)Real-WorldPerformanceandSafetyEvaluation–EnrollingPhaseIFIM48monthresultsDou

ble-blindRandomizedTrial36monthresultsContinuedAccessSafety24monthresultsConfirmatoryTrialvs.Cypher24

monthresultsConfirmatoryTrialvs.Taxus12monthresultsSingleArmTrial9monthresultsReal-WorldPerformanceandSafetyEval

uation–EnrollmentcompletedEndeavorvs.CypherSafetyStudyEnrollingReal-WorldPerformanceandSafetyEvaluation–EnrollingProspe

ctive,MulticenterRegistryAssessingSafetyinaRealWorldPatientPopulationE-FiveRegistryPrimaryEndpoint:MAC

Eat12monthsSecondaryEndpoints:MACEat30daysand6mo,Stentthrombosis,proceduresuccessrate;devicesuccessrate;lesio

nsuccessrateDrugTherapy:ASAandClopidogrel>3monthsZotarolimusDose:10gpermmstentlengthSingleandMultipleCoronaryArteryLesionsStentDiameters:2.25-4.0mmS

tentLength:8/9-30mmN=8,000patients200sitesEurope,AsiaPacific,Israel,SouthAmericaClinical/MACE30d6mo2yr*12mo*Limi

tednumberofcentersandspecificpatientsubset.E-fiveStudyOrganizationAnatomyMedtronicClinicalDepartmentStudySitesSponsor

MedtronicCRAs/MonitorsE-CRFSystemDataManagement&StatisticalAnalysisCoreLabsCECE-FiveRegistry(Recent)MI(%)NonQ-waveMIQwaveMIPriorCABG(%)Unstabl

eAngina(%)DiabetesMellitus(%)PriorPCI(%)PriorMI(%)Age(years)MaleGender(%)n=8318PatientsPatientDemographics

oftotalregistry76.763.30±11.0632.112.221.425.37.532.721.834.0E-FiveRegistryn=8318patientsand10343lesionsLAD(%)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-procedureDS(%)2.41±8.24BaselineAngiograp

hyoftotalregistry(visualmeasurement)E-FiveRegistry21.2(Recent)MI(%)12.2NonQ-waveMI25.3QwaveMI7.0PriorCABG(%)31.2UnstableAngina(%)34.4DiabetesMel

litus(%)23.9PriorPCI(%)35.9PriorMI(%)62.95±11.46Age(years)76.9MaleGender(%)n=1989patientsPatientDemographics1989patientsE-Five

Registryn=1989patientsand2449lesionsLAD(%)47.9B2/CLesions(%)61.7RVD(mm)2.93±0.45LesionLength(mm)18.19±9.90Pre-procedureML

D(mm)0.53±0.41Pre-procedureDS(%)81.93±13.99Post-procedureDS(%)2.01±6.33BaselineAngiographyof1989patients(visualmeasurement)18.19±9.90Lesio

nLength(mm)1.35±0.53Stent:LesionLength28.8Longlesions(>20mm)(%)5.921.016.234.718.04.2MinimumEndeavorStentDiameter

simplanted2.25mm(%)2.5mm(%)2.75mm(%)3.0mm(%)3.5mm(%)4.0mm(%)23.17±11.93TotalStentLength(mm)n=1989patientsand2449lesi

onsE-FiveRegistryProcedureCharacteristicsof1989patientsE-FiveRegistryClinicalOutcomesDefinition•MACEisdefinedasdeath,MI(Qwaveandnon-Q

wave),emergentcardiacbypasssurgery,ortargetlesionrevascularization(repeatPTCAorCABG).•TLRisdefinedasanyclinicallyd

rivenrepeatpercutaneousinterventionofthetargetlesionorbypasssurgeryofthetargetvessel.•TVFisdefinedast

argetvesselrevascularization(definedbelow),recurrentQorNonQ-Wavemyocardialinfarction,orcardiacdeaththatcouldnotbeclearlyattributedtoavesselotherthan

thetargetvessel.Targetvesselfailurewillbereportedwhen:1.RecurrentMIoccursinterritorynotclearlyotherthan

thatofthetargetvessel.2.Cardiacdeathnotclearlyduetoanon-targetvesselendpoint.3.Targetvesselrevascularizationisdetermin

ed.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)NonQ

wave0.6(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)31-3

60days00.2(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)Cli

nicalOutcomesoutto12monthsE-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)Bifurcatio

ns**-%(n)19.3(384)•MyocardialInfarctionupto72hourspriortothePCIandstentingprocedure•**Lesioninvolvingmainand

sidebranch,requiring+2EndeavorstentsE-FiveRegistry30daysn=68212monthsn=649Death(all)-%(n)1.5(10)4.9(32)Cardiac1.2(8)3.5(23)MI(a

ll)-%(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(1

1)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)T

VF-%(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(2

9)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=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(83)TVF-%(n)2.0(18)9.2(80)RVD<2.75mmClinicalOutcomesoutto12monthsE-FiveRegistry30daysn=61

612monthsn=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)UnstableAnginaClinicalOutcomesoutto12mont

hsE-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)NonQwa

ve1.2(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-T

L)-%(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-FiveRe

gistry•InSummary:–TheE-Fiveregistryenrolledpatientsthatrepresentthe“realworld”ofPCI–Therehavebeenindependenteventadjudic

ation,performing10%monitoringtodetectunderreportingofevents–Thefirst2000patientshasprovidedinsightintothesafetyand

efficacyoftheEndeavorDESinamorecomplexpatientpopulation•Conclusions:–TheEndeavorDrugElutingStentwasasso

ciatedwithalowMACEandTLRinthefirst1989patientsstudiedoutto12months–Despitetherelativecomplexityofthispatientcohortthesafetyoutcomes

–cardiacdeath,MIandstentthrombosiswerealsolow–TheseresultsareconsistentwiththeoutcomesreportedwiththeEndeavorDESintrialsenrollingmoremoderatele

sionsandpatientsConclusionFuWaiHospitalinE-Five•Thebestperformerinpatientenrollmentbasedonaveragepatientrecruit

edperweek:13+patientsperweek•Excellentcompliance–Completesourcedocumentavailable–Follow-upstrictlywithinprotocoltimeframe–AEreportingfollowing

applicablerequirements•Selectedsiteswereinvitedforanextendedtwo-yearfollow-upbasedonpatientenrollmentspeedandstudyquality,FWHisoneoftheonlyt

hreehospitalsinAsiaPacificreceivedtheinvitationPROTECT-STUDYDESIGNProspective,multi-center,randomized,two-arm,open-labeltrialPatie

nts:SingleandMultipleCoronaryArteryLesionsCypherStentN=44008,800patients200sitesClinicalFUProcedure30d1yr2yrs3yrs4yrs5yrsAnti-plateletth

erapyfor3–12monthsPrimaryendpointat3yearsPrimaryEndpoint:Overallstentthrombosisat3yearsdefinedasdefiniteandprobableaccordingtotheARCdef

initioncriteriaMainSecondaryEndpoint:compositeendpointoftotaldeathorcardiacdeathcombinedwiththenumber

ofpatientswithallnon-fatalMIaswellasthenumberofpatientswithlargenon-fatalMIat3yearsAdditionalSecondaryEndpoints(at30Days,6Mo,1,1

½,2,2½,3,4,5Yrs):TotalDeathandsubcategoriesofDeathLargeandallMI,Stentthrombosisdefinedasdefinite,probabl

eandpossible,Compositescoreofclinicaloutcomes(death,myocardialinfarction,strokeandrevascularization),MajorAdverseCardiacandCerebralEvents(MAC

CE)Stroke(hemorrhagicinnaturewhileonclopidogrel),Bleedingcomplicationsingeneral,TLR,TVR,non-TVR,Proceduralsuccess,Devicesuccess,Les

ionsuccess6mo1½yr2½yrEndeavorStentN=4400ASSUMPTIONSPRIMARYENDPOINT419631341.5%0.62.5%Power(1-)90%Power(1-)80%PatientsperarmENDEAVORHR

CYPHERThestent-specificoutcomeofthrombosisoffersbestpowertodetectdifferencesbetweendifferentDESWith4196ptspera

rm,thetrialispoweredtodetecta1%absolutereductioninstentthrombosisratesPROTECTSAMPLESIZECALCULATIONPrimaryendpoint:3yearF

reedomfromstentthrombosis(ARCdefiniteandprobable)•Ho:lEndeavor=lCypher•Ha:lEndeavor≠lCypherAssumptions•TreatmenteffecthazardratiolEndeavor/lCyp

her=0.6•Power:90%•Two-sidedalphaerror:5%•3interimanalysesThecalculatedsamplesizeis4196patientsperarm;Atotalof8800patientswillbeenrolledaccounti

ngfor<10%losttofollow-up.PROTECTStudyOrganizationAnatomyMedtronicClinicalDepartment&CROStudySitesSponsorMedtronicCRA

s*/MonitorsRandomizationSystemE-CRFsystemDataManagement&StatisticalAnalysisCoreLabsCRA:ClinicalResearchAs

sociateCEC:ClinicalEventCommitteeCEC*PROTECTGlobalUpdateWaitingforMedtronicEuropetosendmethelatestglobalnewsletterinwhichFuwaiwillberecogniz

edandthankedforitsstudyperformance.Thisslidewillbeupdatedsoon…FuWaiHospitalinPROTECT•95patientsenrolledin15weeks•Studydata

qualityrecognizedthroughtwostudycomplianceassessmentFWH’sClinicalResearchTeam•Cultivateresearchatmospherethroughcontinuousclinicalstudytrainingandpa

rticipationinhighstandardclinicaltrials•ClearlydefinerolesandresponsibilitiestoensureaccountabilityClinica

lStudyCathLabDirectorCathLabOperatorsStudyCoordinatorappointedfromthephysiciangroupTechniciansforQCACDmakingDedic

atedStudyF/UTeamCathLabNursesforDataEntryTopQualityWorkWinsCredibilityinTrueGlobalClinicalTrials•Ensurethatthewholeresearchteamreceivescomprehensi

vetrainingonanyspecificstudy•Dedicatedstudycoordinatorandclearlydefinedrolesandresponsibilitiestoenfo

rceaccountability•Followingtheglobalstandardongoodclinicalpractice•Impressivepatientenrollmentpaceprovidedstudydataq

ualityisnotcompromisedProspective,MulticenterRegistryAssessingSafetyinaRealWorldChinesePatientPopulationChinaEndeavo

rRegistry(Endeavor-China)PrimaryEndpoint:MACEat12monthsSecondaryEndpoints:MACEat30daysand6mo,Stentthrom

bosis,proceduresuccessrate;devicesuccessrate;lesionsuccessrateDrugTherapy:ASAandClopidogrel>3monthsZotarolimusDose:10gpermmstentlengthSingleandM

ultipleCoronaryArteryLesionsStentDiameters:2.25-4.0mmStentLength:8/9-30mmN=2,200patients32sitesacrossChinaClinical/MACE30d6mo2yr*12m

o*Limitednumberofcentersandspecificpatientsubset.GoalsofEndeavorChinaRegistry•通过入选“真实世界”中国病人以扩展对Endeavor支架的临床认识Toexpan

dtheclinicalknowledgebaseforEndeavorstentdeliverysystembyincluding‘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,fo

rexamplepatientswithdiabetesmellitus,smallvesselsandlonglesionsChinaEndeavorRegistrySampleSizeCalculation•Theprimaryendpointis

theMajorAdverseCardiacEvents(MACE)rateat1yearpost-procedure.Thisendpointisdefinedasdeath,myocardialinfarction(Qwavean

dnon-Qwave),emergentcardiacbypasssurgery,ortargetlesionrevascularization(repeatPTCAorCABG).•Previousstudieshavesuggestedthatt

heMACErateatoneyearisapproximately11%.Underthisassumption,asamplesizeof2200willprovide95%confidencethattherat

eofMACEat1yearwillnotexceed12.4%.•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ChinaEndeavorRegistryStudyProcessPrestudypreparationSiteInitiationTrainingP

atientEnrollmentStudyCloseoutSolveDataQueriesGenerateStudyReport&PublicationPICProcedureandFollow-upCRFDataEntryChinaEndeavorRegistry•Studymana

gementfollowingMedtronicUS/Europestandard•Monitoringofabout50%ofpatients•Datamanagementandstatisticalan

alysisoverseenbyMedtronicUS•Aimingfordatareleaseinmajorinternationalanddomesticconferences•Targetingonpublicationintoptierjournals研究进展S

tudyprogressbyMarch,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,thet

openrollers：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7HotTopicsonChinaEndeavorRegis

try•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