ACE研究將指導(dǎo)心血管疾病全面防治的新策略

ACE研究將指導(dǎo)心血管疾病全面防治的新策略目前一頁(yè)\總數(shù)二十三頁(yè)\編于九點(diǎn)ACETrialManagementCoordinatingCentreDiabetesTrialsUnit,UniversityofOxfordACEChineseProjectOfficeOxfordUniversity(Beijing)Science&TechnologyLimitedFunding&StudyMedicationBayerHealthCareChina&BayerScheringPharma目前二頁(yè)\總數(shù)二十三頁(yè)\編于九點(diǎn)StudyDesignDouble-blind,multi-centre,randomised,controlled,clinicaloutcometrialcomparingacarboseversusplacebo

InvestigatordesignedandledacademictrialIndependentdatacollection,analysisandreportingConductedinMainlandChinaandHongKong7,500patientsin~150cardiovascularcentresMinimumpatientfollowupfouryearsEventdriven(904adjudicatedprimaryevents)目前三頁(yè)\總數(shù)二十三頁(yè)\編于九點(diǎn)RuryHolman UK Diabetologist (Chair)DaYiHu China Cardiologist (Co-Chair)ChangYuPan China Diabetologist (Co-Chair)JiaLunChen China Diabetologist (Honouredadviser)JulianaChan HongKong DiabetologistJean-LouisChiasson Canada DiabetologistJunBoGe China CardiologistHertzelGerstein Canada DiabetologistJohnMcMurray UK CardiologistLarsRydén Sweden CardiologistMichalTendera Poland CardiologistJaakkoTuomilehto Finland EpidemiologistWenYingYang China DiabetologistJoanneKeenan UK DTUProjectManagerDieterNeuser Germany BayerProjectManagerThorstenPetruschke Germany BayerProjectManagerACESteeringCommittee目前四頁(yè)\總數(shù)二十三頁(yè)\編于九點(diǎn)MajorInclusionCriteriaConfirmedcardiovasculardisease(CVD)HistoryofmyocardialinfarctionPreviousunstableanginaCurrentstableanginaImpairedglucosetolerance(IGT)onanoralglucosetolerancetestwith:Fastingplasmaglucose<7.0mmol/l2-hourplasmaglucose≥7.8and≤11.1mmol/lMaleorfemale,aged50yearsormoreStabledrugtherapyforCVDwithnoplannedcoronary,cerebrovascularorperipheralarterialrevascularisationWritteninformedconsent目前五頁(yè)\總數(shù)二十三頁(yè)\編于九點(diǎn)MajorExclusionCriteriaHistoryofdiabetes(exceptgestationaldiabetes)Myocardialinfarction,unstableangina,strokeoraTIAintheprevious3monthsNYHAclassIIIorIVheartfailureHepaticdisease(ALT>3xULN)Severerenalimpairment

(eGFR<30ml/min/1.73m2)GastrointestinalproblemsoralphaglucosidaseinhibitorintolerancePregnancyorpossibilityofpregnancyThoughtbytheinvestigatortobeunsuitable目前六頁(yè)\總數(shù)二十三頁(yè)\編于九點(diǎn)ACEPrimaryEndpointComposite“hard”CVDendpointDefinedasthetimetothefirstoccurrenceafterrandomisationofanyof:CardiovasculardeathResuscitatedcardiacarrestNon-fatalmyocardialinfarctionNon-fatalstrokeAnEndpointAdjudicationCommittee,maskedtotherapyallocation,willreviewallpotentialCVDendpointsindependently.目前七頁(yè)\總數(shù)二十三頁(yè)\編于九點(diǎn)New-onsettype2diabetes,confirmedbytwosuccessivediagnosticplasmaglucosevaluesFPG≥7.0mmol/l

and/or2HPG≥11.1mmol/lACESecondaryEndpoint目前八頁(yè)\總數(shù)二十三頁(yè)\編于九點(diǎn)AllcausemortalityExtendedCVDendpointofcardiovasculardeath,resuscitatedcardiacarrest,non-fatalmyocardialinfarction,fatalornon-fatalstrokeandhospitalisationforheartfailureorforunstableangina.EachcomponentwillalsobeanalysedindividuallyEvidenceofnon-alcoholicfattyliverdisease(NAFLD)asjudgedbyALTchangesDevelopmentofimpairedrenalfunction(eGFR<60ml/minute/1.73m2)ordoublingofbaselinecreatinineHealthEconomicevaluationOtherSecondaryOutcomes目前九頁(yè)\總數(shù)二十三頁(yè)\編于九點(diǎn)SampleSizeEstimationAssumesAprimaryeventrateof3.5%peryearA20%relativereductioncomparedwithplaceboAn18monthaccrualperiodAlphaof5%For90%PowerThestudyrequires7,268patientswithaminimumof904adjudicatedprimaryeventsAtotalof7,500patientswillberecruitedtoallowforanoverall3%loss-to-followup目前十頁(yè)\總數(shù)二十三頁(yè)\編于九點(diǎn)DoubleBlindInterventionInadditiontooptimisedCVDtherapy:Randomisedto:Acarbose,50mgthreetimesaday

orMatchingplacebo,threetimesadayTabletstobetakenwithmealsUse‘Startlow,goslow’dosetitration目前十一頁(yè)\總數(shù)二十三頁(yè)\編于九點(diǎn)ACEStudyFlowChartMinimumof904adjudicatedprimaryeventsrequired7,500CVD

orACS目前十二頁(yè)\總數(shù)二十三頁(yè)\編于九點(diǎn)OptimisationofCardiovascularTherapyCVDtherapywillbeoptimisedduringthefour-week,single-blind,placeborun-inperiodtoensureitconformswithinternationalguidelinesfortreatingpatientswithestablishedCVDThatis:Antiplatelettherapy,unlesscontraindicatedornottoleratedAstatin,unlesscontraindicatedornottoleratedACEinhibitor,beta-blocker,and/orantihypertensivetherapyifconsideredindicatedbytheinvestigator目前十三頁(yè)\總數(shù)二十三頁(yè)\編于九點(diǎn)SafetyTheACEtrialwillbeconductedtoICH-GCPstandardsLiverfunctionwillbemonitoredannuallySeriousUnexpectedSuspectedAdverseReactions(SUSARs)willundergoexpeditedreportingAnIndependentDataSafetyMonitoringBoard(DSMB)willreviewunblindedsafetydataatleastsix-monthly目前十四頁(yè)\總數(shù)二十三頁(yè)\編于九點(diǎn)TheACEtrialisenrolling~150cardiovascularcentresinMainlandChinaandHongKingEachcentreisexpectedtorecruitapproximately50patients(minimumof35patients)Recruitmentiscompetitiveandwillclosewhen7,500patientshavebeenrandomisedTheACEtrialresultsareexpectedin2014Schedule目前十五頁(yè)\總數(shù)二十三頁(yè)\編于九點(diǎn)ClinicalCentreRequirementsQualifiedresearchstaffandappropriatefacilitiestosafelyandproperlyconductthetrialinaccordancewithICHGCPguidelinesProvenclinicaltrialexperienceorwillingnesstoacquirethenecessaryskillsAccesstoasufficienteligiblepatientstoensurearound50canbeenrolledandkeptinthetrialforaminimumfollowedupperiodoffouryearsAbletoperformOralGlucoseToleranceTests(OGTTs)andotherroutineclinicalmeasurementsIn