Endeavor 在中国临床试验的案例分析ppt课件

1、以高质量在真正的世界级临床实验中建立声誉：以高质量在真正的世界级临床实验中建立声誉： Endeavor 在中国临床实验的案例分析在中国临床实验的案例分析Top Quality Work Wins Credibility in True Global Clinical Trials - A Case Study of Endeavor Clinical Programs in China阜外心血管病医院介入导管室阜外心血管病医院介入导管室徐徐 波波Story FlowMedtronic global Endeavor clinical program overview, to highlight

2、 E-five, PROTECT, China Endeavor Registry, three studies China has been participating inMore information on E-five, FWHs performance in E-fiveMore information on PROTECT, FWHs performance in PROTECT (AP newsletter snapshot and Global newsletter snapshot reflecting recognition on FWHs performance)Sum

3、marize what FWH has done right in the above global trials to establish a good reputation on clinical studyIntroducing China Endeavor Registry (CER), use what FWH has done right in E-five and PROTECT to encourage sites participating in CER to speed up patient enrollment while ensuring data qualityRan

4、domized Clinical Study Organization AnatomyStudy Management TeamStudy SitesSponsorCRAs*/MonitorsRandomization SystemData Management & Statistical AnalysisCore LabsCEC*CRA: Clinical Research AssociateCEC: Clinical Event CommitteeClinical Study Process Pre study preparationSite Initiation Training

5、Patient EnrollmentStudy Close outSolve Data QueriesGenerate Study Report &PublicationPICRandomizationProcedure and Follow-upCRF Data EntryENDEAVOR Clinical Program UpdatePhase I FIM 48 month resultsDouble-blind Randomized Trial36 month resultsContinued Access Safety24 month resultsConfirmatory T

6、rial vs. Cypher24 month resultsConfirmatory Trial vs. TaxusEnrollment completedSingle Arm Trial30 days resultsReal-World Performance and Safety Evaluation Enrollment completedEndeavor vs. Cypher Safety StudyEnrollingENDEAVOR I (100 patients)ENDEAVOR II (1200 patients)ENDEAVOR II CA Registry(300 pati

7、ents)ENDEAVOR III(436 patients)ENDEAVOR IV(1548 patients)ENDEAVOR Japan(99 patients)E-Five Registry(8000 patients)PROTECT(8800 patients)China Endeavor Registry(2200 patients)Real-World Performance and Safety Evaluation EnrollingPhase I FIM 48 month resultsDouble-blind Randomized Trial36 month result

8、sContinued Access Safety24 month resultsConfirmatory Trial vs. Cypher24 month resultsConfirmatory Trial vs. Taxus12 month resultsSingle Arm Trial9 month resultsReal-World Performance and Safety Evaluation Enrollment completedEndeavor vs. Cypher Safety StudyEnrollingReal-World Performance and Safety

9、Evaluation EnrollingE-Five Registry*Limited number of centers and specific patient subset.E-five Study Organization AnatomyMedtronic Clinical DepartmentStudy SitesSponsorMedtronicCRAs/MonitorsE-CRF SystemData Management & Statistical AnalysisCore LabsCECE-Five Registry(Recent) MI (%)Non Q-wave M

10、IQ wave MIPrior CABG (%)Unstable Angina (%)Diabetes Mellitus (%)Prior PCI (%)Prior MI (%)Age (years)Male Gender (%)n = 8318 Patients76.763.3011.0625.37.532.721.834.0E-Five Registryn=8318 patients and 10343 lesionsLAD (%)46.6B2/C Lesions (%)60.3RVD (mm)2.930.47Lesion Length (mm)18.5010.60

11、Pre-procedure MLD (mm)0.500.41Pre-procedure DS (%)82.8413.51Post-procedure DS (%)2.418.24E-Five Registry21.2(Recent) MI (%)12.2Non Q-wave MI25.3Q wave MI7.0Prior CABG (%)31.2Unstable Angina (%)34.4Diabetes Mellitus (%)23.9Prior PCI (%)35.9Prior MI (%)62.9511.46Age (years)76.9Male Gender (%)n = 1989

12、patientsE-Five Registryn=1989 patients and 2449 lesionsLAD (%)47.9B2/C Lesions (%)61.7RVD (mm)2.930.45Lesion Length (mm)18.199.90Pre-procedure MLD (mm)0.530.41Pre-procedure DS (%)81.9313.99Post-procedure DS (%)2.016.3318.199.90Lesion Length (mm)1.350.53Stent: Lesion Length28.8Long lesions (20 mm) (%

13、)5.921.016.234.718.04.2 Minimum Endeavor Stent Diameters implanted 2.25 mm (%) 2.5 mm (%) 2.75 mm (%) 3.0 mm (%) 3.5 mm (%) 4.0 mm (%)23.1711.93Total Stent Length (mm)n=1989 patients and 2449 lesionsE-Five RegistryE-Five Registry Clinical Outcomes DefinitionMACE is defined as death, MI (Q wave and n

14、on-Q wave), emergent cardiac bypass surgery, or target lesion revascularization (repeat PTCA or CABG).TLR is defined as any clinically driven repeat percutaneous intervention of the target lesion or bypass surgery of the target vessel.TVF is defined as target vessel revascularization (defined below)

15、, recurrent Q or Non Q-Wave myocardial infarction, or cardiac death that could not be clearly attributed to a vessel other than the target vessel. Target vessel failure will be reported when:1. Recurrent MI occurs in territory not clearly other than that of the target vessel.2. Cardiac death not cle

16、arly due to a non-target vessel endpoint.3. Target vessel revascularization is determined.E-Five Registry30 daysn=198912 monthsn=1989Death (all) - % (n)0.8 (16)2.9 (55) Cardiac0.7 (14)2.0 (38)MI (all) - % (n)0.8 (15)1.3 (25) Q Wave0.2 (4)0.4 (8) Non Q wave0.6 (11)0.9 (17)Death (cardiac) + MI (all) -

17、 % (n)1.4 (27)3.0 (57)Stent Thrombosis (all) - % (n)0.8 (16)1.1 (20) 0-30 days 0.8 (16)0.8 (16) 31-360days 00.2 (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)Clinical Outcomes out to 12 monthsE-Fiv

18、e RegistryComplex SubsetsSample size n=1989Diabetics - % (n) Insulin Dependent - % (n) Non Insulin Dependent % (n)34.4 (684)9.2 (182)25.2 (502)Lesions 20mm - % (n)34.4 (685)RVD 20mm Clinical Outcomes out to 12 monthsE-Five Registry30 daysn=91312 monthsn=866Death (all) - % (n)1.1 (10)3.5 (30) Cardiac

19、0.9 (8)2.5 (22)MI (all) - % (n)1.1 (10)2.0 (17) Q Wave0.2 (2)0.6 (5) Non Q wave0.9 (8)1.4 (12)Death (cardiac) + MI (all) - % (n)1.8 (16)3.9 (34)Stent Thrombosis (all) - % (n)1.1 (10)1.5 (13) 0-30 days 1.1 (10)1.2 (10) 31-360days 00.3 (3)TLR - % (n)0.7 (6)5.8 (50)TVR (non-TL) - % (n)0.1 (1)1.3 (11)TV

20、R - % (n)0.7 (6)6.8 (59)MACE - % (n)2.2 (20)9.6 (83)TVF - % (n)2.0 (18)9.2 (80)RVD 2.75mm Clinical Outcomes out to 12 monthsE-Five Registry30 daysn=61612 monthsn=579Death (all) - % (n)1.0 (6)2.6 (15) Cardiac1.0 (6)1.7 (10)MI (all) - % (n)0.6 (4)0.9 (5) Q Wave0.2 (1)0.2 (1) Non Q wave0.5 (3)0.7 (4)De

21、ath (cardiac) + MI (all) - % (n)1.5 (9)2.4 (14)Stent Thrombosis (all) - % (n)0.8 (5)1.2 (7) 0-30 days 0.8 (5)0.9 (5) 31-360days 00.3 (2)TLR - % (n)0.3 (2)3.8 (22)TVR (non-TL) - % (n)0 0.3 (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)Unstable Angina Clinical Outco

22、mes out to 12 monthsE-Five Registry30 daysn=42112 monthsn=393Death (all) - % (n)2.1 (9)5.3 (21) Cardiac1.7 (7)4.3 (17)MI (all) - % (n)1.2 (5)2.5 (10) Q Wave00.8 (3) Non Q wave1.2 (5)1.8 (7)Death (cardiac) + MI (all) - % (n)2.6 (11)5.9 (23)Stent Thrombosis (all) - % (n)1.4 (6)1.8 (7) 0-30 days 1.4 (6

23、)1.5 (6) 31-360days 00.3 (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)Recent MI Clinical Outcomes out to 12 monthsE-Five Registry30 daysn=38412 monthsn=359Death (all) - % (n)1.0 (4)4.2 (15) Cardiac1.0 (4)3.3 (

24、12)MI (all) - % (n)1.3 (5)2.2 (8) Q Wave0.3 (1)0.3 (1) Non Q wave1.0 (4)1.9 (7)Death (cardiac) + MI (all) - % (n)2.1 (8)4.5 (16)Stent Thrombosis (all) - % (n)1.3 (5)1.7 (6) 0-30 days 1.3 (5)1.4 (5) 31-360days 00.3 (1)TLR - % (n)0.5 (2)4.7 (17)TVR (non-TL) - % (n)01.9 (7)TVR - % (n)0.5 (2)6.4 (23)MAC

25、E - % (n)2.1 (8)8.9 (32)TVF - % (n)2.1 (8)9.5 (34)Bifurcation lesions Clinical Outcomes out to 12 monthsE-Five RegistryIn Summary:The E-Five registry enrolled patients that represent the “real world of PCI There have been independent event adjudication, performing 10% monitoring to detect underrepor

26、ting of eventsThe first 2000 patients has provided insight into the safety and efficacy of the Endeavor DES in a more complex patient populationConclusions:The Endeavor Drug Eluting Stent was associated with a low MACE and TLR in the first 1989 patients studied out to 12 monthsDespite the relative c

27、omplexity of this patient cohort the safety outcomes cardiac death, MI and stent thrombosis were also lowThese results are consistent with the outcomes reported with the Endeavor DES in trials enrolling more moderate lesions and patientsFu Wai Hospital in E-Five The best performer in patient enrollm

28、ent based on average patient recruited per week: 13+ patients per week Excellent compliance Complete source document available Follow-up strictly within protocol timeframe AE reporting following applicable requirements Selected sites were invited for an extended two-year follow-up based on patient e

29、nrollment speed and study quality, FWH is one of the only three hospitals in Asia Pacific received the invitationPROTECT - STUDY DESIGN Prospective, multi-center, randomized, two-arm, open-label trialPatients: Single and Multiple Coronary Artery LesionsCypher StentN=44008,800 patients200 sitesClinic

30、al FUProcedure30d1yr2yrs3yrs4yrs5yrsAnti-platelet therapy for 312 months Primary endpoint at 3 yearsPrimary Endpoint: Overall stent thrombosis at 3 years defined as definite and probable according to the ARC definition criteria Main Secondary Endpoint: composite endpoint of total death or cardiac de

31、ath combined with the number of patients with all non-fatal MI as well as the number of patients with large non-fatal MI at 3 yearsAdditional Secondary Endpoints (at 30 Days, 6 Mo, 1, 1, 2, 2, 3, 4, 5 Yrs): Total Death and subcategories of Death Large and all MI, Stent thrombosis defined as definite

32、, probable and possible, Composite score of clinical outcomes (death, myocardial infarction, stroke and revascularization), Major Adverse Cardiac and Cerebral Events (MACCE)Stroke (hemorrhagic in nature while on clopidogrel), Bleeding complications in general, TLR, TVR, non-TVR, Procedural success,

33、Device success, Lesion success 6mo1yr2yrEndeavor StentN=4400ASSUMPTIONS PRIMARY ENDPOINT419631341.5%0.62.5%Power (1-)90%Power (1-)80%Patients per arm ENDEAVORHR CYPHERThe stent-specific outcome of thrombosis offers best power to detect differences between different DES With 4196 pts per arm, the tri

34、al is powered to detect a 1% absolute reduction in stent thrombosis ratesPROTECT SAMPLE SIZE CALCULATIONPrimary endpoint: 3 year Freedom from stent thrombosis (ARC definite and probable)Ho: l Endeavor = l Cypher Ha: l Endeavor l CypherAssumptions Treatment effect hazard ratio l Endeavor / l Cypher =

35、 0.6 Power: 90% Two-sided alpha error: 5% 3 interim analysesThe calculated sample size is 4196 patients per arm; A total of 8800 patients will be enrolled accounting for 10% lost to follow-up.PROTECT Study Organization AnatomyMedtronic Clinical Department& CROStudy SitesSponsorMedtronicCRAs*/Mon

36、itorsRandomization SystemE-CRF systemData Management & Statistical AnalysisCore LabsCRA: Clinical Research AssociateCEC: Clinical Event CommitteeCEC*PROTECT Global UpdateWaiting for Medtronic Europe to send me the latest global newsletter in which Fuwai will be recognized and thanked for its stu

37、dy performance.This slide will be updated soonFu Wai Hospital in PROTECT 95 patients enrolled in 15 weeks Study data quality recognized through two study compliance assessmentFWHs Clinical Research Team Cultivate research atmosphere through continuous clinical study training and participation in hig

38、h standard clinical trials Clearly define roles and responsibilities to ensure accountability Clinical StudyCath Lab DirectorCath Lab OperatorsStudy Coordinator appointed from the physician groupTechnicians for QCA CD makingDedicated Study F/U TeamCath Lab Nurses for Data EntryTop Quality Work Wins

39、Credibility in True Global Clinical Trials Ensure that the whole research team receives comprehensive training on any specific study Dedicated study coordinator and clearly defined roles and responsibilities to enforce accountability Following the global standard on good clinical practice Impressive

40、 patient enrollment pace provided study data quality is not compromisedChina Endeavor Registry (Endeavor-China)*Limited number of centers and specific patient subset.Goals of Endeavor China Registry 经过入选“真实世界中国病人以扩展对Endeavor支架的临床认识 To expand the clinical knowledge base for Endeavor stent delivery sy

41、stem by including real world patients in China 评价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 To assess the event rate in Chinese patients known to have a higher risk of major adverse cardiac events, for example patients with diabetes mellitus, small vessels and long lesionsChina Endeavor Registry Sam

42、ple Size Calculation The primary endpoint is the Major Adverse Cardiac Events (MACE) rate at 1 year post-procedure. This endpoint is defined as death, myocardial infarction (Q wave and non-Q wave), emergent cardiac bypass surgery, or target lesion revascularization (repeat PTCA or CABG). Previous studies have suggested that the MACE rate at one year is approximately 11%. Under this assumptio