1、Story Flow,Medtronic global Endeavor clinical program overview, to highlight 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 a
2、nd Global newsletter snapshot reflecting recognition on FWHs performance)Summarize 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 partic
3、ipating in CER to speed up patient enrollment while ensuring data quality,Randomized Clinical Study Organization Anatomy,CRA: Clinical Research AssociateCEC: Clinical Event Committee,Clinical Study Process,Pre study preparation,Site Initiation Training,Patient Enrollment,Study Close out,Solve Data Q
4、ueries,Generate Study Report &Publication,PIC,Randomization,Procedure and Follow-up,CRF Data Entry,ENDEAVOR Clinical Program Update,Phase I FIM 48 month results,Double-blind Randomized Trial36 month results,Continued Access Safety24 month results,Confirmatory Trial vs. Cypher24 month results,Confirm
5、atory Trial vs. TaxusEnrollment completed,Single Arm Trial30 days results,Real-World Performance and Safety Evaluation Enrollment completed,Endeavor vs. Cypher Safety StudyEnrolling,Real-World Performance and Safety Evaluation Enrolling,Prospective, Multicenter Registry AssessingSafety in a Real Wor
6、ld Patient Population,E-Five Registry,Primary Endpoint: MACE at 12 monthsSecondary Endpoints: MACE at 30 days and 6 mo, Stent thrombosis, procedure success rate; device success rate; lesion success rateDrug Therapy: ASA and Clopidogrel 3 monthsZotarolimus Dose: 10 g per mm stent length,Single and Mu
7、ltiple Coronary Artery LesionsStent Diameters: 2.25-4.0 mmStent Length: 8/9-30 mm,N = 8,000 patients200 sitesEurope, Asia Pacific, Israel, South America,Clinical/MACE,30d,6mo,2yr*,12mo,*Limited number of centers and specific patient subset.,E-five Study Organization Anatomy,E-Five Registry,(Recent)
8、MI (%),Non Q-wave MI,Q wave MI,Prior CABG (%),Unstable Angina (%),Diabetes Mellitus (%),Prior PCI (%),Prior MI (%),Age (years),Male Gender (%),n = 8318 Patients,Patient Demographics of total registry,E-Five Registry,Baseline Angiography of total registry (visual measurement),E-Five Registry,21.2,(Re
9、cent) MI (%),12.2,Non Q-wave MI,25.3,Q wave MI,7.0,Prior CABG (%),31.2,Unstable Angina (%),34.4,Diabetes Mellitus (%),23.9,Prior PCI (%),35.9,Prior MI (%),62.9511.46,Age (years),76.9,Male Gender (%),n = 1989 patients,Patient Demographics 1989 patients,E-Five Registry,Baseline Angiography of 1989 pat
10、ients (visual measurement),18.199.90,Lesion Length (mm),1.350.53,Stent: Lesion Length,28.8,Long lesions (20 mm) (%),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 (%),23.1711.93,Total Stent Length (mm),n=1989 patients
11、 and 2449 lesions,E-Five Registry,Procedure Characteristics of 1989 patients,E-Five Registry Clinical Outcomes,DefinitionMACE is defined as death, MI (Q wave and non-Q wave), emergent cardiac bypass surgery, or target lesion revascularization (repeat PTCA or CABG).TLR is defined as any clinically dr
12、iven repeat percutaneous intervention of the target lesion or bypass surgery of the target vessel.TVF is defined as target vessel revascularization (defined below), recurrent Q or Non Q-Wave myocardial infarction, or cardiac death that could not be clearly attributed to a vessel other than the targe
13、t 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 clearly due to a non-target vessel endpoint.3. Target vessel revascularization is determined.,E-Five Registry,Clinical Outcomes out to 12 mo
14、nths,E-Five Registry,Complex Subsets,Myocardial Infarction up to 72 hours prior to the PCI and stenting procedure* Lesion involving main and side branch, requiring +2 Endeavor stents,E-Five Registry,Diabetics Clinical Outcomes out to 12 months,E-Five Registry,Lesions 20mm Clinical Outcomes out to 12
15、 months,E-Five Registry,RVD 2.75mm Clinical Outcomes out to 12 months,E-Five Registry,Unstable Angina Clinical Outcomes out to 12 months,E-Five Registry,Recent MI Clinical Outcomes out to 12 months,E-Five Registry,Bifurcation lesions Clinical Outcomes out to 12 months,E-Five Registry,In Summary:The
16、E-Five registry enrolled patients that represent the “real world” of PCI There have been independent event adjudication, performing 10% monitoring to detect underreporting of eventsThe first 2000 patients has provided insight into the safety and efficacy of the Endeavor DES in a more complex patient
17、 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 complexity of this patient cohort the safety outcomes cardiac death, MI and stent thrombosis were also lowThese results are consistent
18、 with the outcomes reported with the Endeavor DES in trials enrolling more moderate lesions and patients,Conclusion,Fu Wai Hospital in E-Five,The best performer in patient enrollment based on average patient recruited per week: 13+ patients per weekExcellent compliance Complete source document avail
19、able Follow-up strictly within protocol timeframe AE reporting following applicable requirementsSelected sites were invited for an extended two-year follow-up based on patient enrollment speed and study quality, FWH is one of the only three hospitals in Asia Pacific received the invitation,PROTECT -
20、 STUDY DESIGN Prospective, multi-center, randomized, two-arm, open-label trial,Patients: Single and Multiple Coronary Artery Lesions,Cypher StentN=4400,8,800 patients200 sites,Clinical FU,Procedure,30d,1yr,2yrs,3yrs,4yrs,5yrs,Anti-platelet therapy for 312 months Primary endpoint at 3 years,Primary E
21、ndpoint: 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 death combined with the number of patients with all non-fatal MI as well as the number of patients with large n
22、on-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, probable and possible, Composite score of clinical outcomes (death, myocardial infarction, stroke and revas
23、cularization), Major Adverse Cardiac and Cerebral Events (MACCE)Stroke (hemorrhagic in nature while on clopidogrel), Bleeding complications in general, TLR, TVR, non-TVR, Procedural success, Device success, Lesion success,6mo,1yr,2yr,Endeavor StentN=4400,ASSUMPTIONS PRIMARY ENDPOINT,4196,3134,1.5%,0
24、.6,2.5%,Power (1-)90%,Power (1-)80%,Patients per arm,ENDEAVOR,HR,CYPHER,The stent-specific outcome of thrombosis offers best power to detect differences between different DES With 4196 pts per arm, the trial is powered to detect a 1% absolute reduction in stent thrombosis rates,PROTECT SAMPLE SIZE C
25、ALCULATION,Primary 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 = 0.6 Power: 90% Two-sided alpha error: 5% 3 interim analysesThe calculated sample size is 419
26、6 patients per arm; A total of 8800 patients will be enrolled accounting for 3 monthsZotarolimus Dose: 10 g per mm stent length,Single and Multiple Coronary Artery LesionsStent Diameters: 2.25-4.0 mmStent Length: 8/9-30 mm,N = 2,200 patients32 sites across China,30d,6mo,2yr*,12mo,*Limited number of
27、centers and specific patient subset.,Goals of Endeavor China Registry,通过入选“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 system by including real world patients in China 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 To assess the event rate in Chinese
28、patients known to have a higher risk of major adverse cardiac events, for example patients with diabetes mellitus, small vessels and long lesions,China Endeavor Registry Sample Size Calculation,The primary endpoint is the Major Adverse Cardiac Events (MACE) rate at 1 year post-procedure. This endpoi
29、nt 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 assumption, a sample size of 2200 will pro
30、vide 95% confidence that the rate of MACE at 1 year will not exceed 12.4%. This sample size allows for a 10% rate of lost to follow-up.,China Endeavor Registry,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,China Endeavor Registry Study Process,Pre study preparatio
31、n,Site Initiation Training,Patient Enrollment,Study Close out,Solve Data Queries,Generate Study Report &Publication,PIC,Procedure and Follow-up,CRF Data Entry,China Endeavor Registry,Study management following Medtronic US/Europe standardMonitoring of about 50% of patientsData management and statist
32、ical analysis overseen by Medtronic USAiming for data release in major international and domestic conferencesTargeting on publication in top tier journals,研究进展Study progress by March, 2008,第一个病人入选：沈阳军总 2007年11月 First Pat. In: Nov. 2007 by SY Military入选720病人, 启动医院30家720 patients enrolled from 30 acti
33、vated hospitals入选病人数最多, the top enrollers： 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), the fastest enroller (weekly)： 广东省人民医院 9 北京安贞医院 8 沈阳军总 7,Hot Topics on China Endeavor Registry,PIC unsignedDelayed data entryNo dedicated coordinator overseeing the study,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,
