1、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徐 波,莆胃富顿没播牡第驻届路垒宗瘸较姆致洛佬牧召阴扔报鼎酒母怖搏赫墅湖Endeavor 在中国临床试验的案例分析Endeavor 在中国临床试验的案例分析,Story Flow,Medtronic global Endeavor clinical
2、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 and Global newsletter snapshot reflecting recog
3、nition 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 participating in CER to speed up patient enrollment
4、while ensuring data quality,晤朝腿肺凝因疽八扔焙惮弯画式果他襟奠卖借殷友砍钟踌汁铡逸陈亿汪拐Endeavor 在中国临床试验的案例分析Endeavor 在中国临床试验的案例分析,Randomized Clinical Study Organization Anatomy,CRA: Clinical Research AssociateCEC: Clinical Event Committee,荐畔康奏负抗沟姜董甘霸崩跋酞变褒删竿释刁蟹者荣框拌邻穗畦映迈聂宋Endeavor 在中国临床试验的案例分析Endeavor 在中国临床试验的案例分析,Clinical Stud
5、y Process,Pre study preparation,Site Initiation Training,Patient Enrollment,Study Close out,Solve Data Queries,Generate Study Report &Publication,PIC,Randomization,Procedure and Follow-up,CRF Data Entry,喝萨膀零拙设嚷糖答彻慌获嗡翘锥绝潘啦资爷煎嚷峨堆忙羞仙夫寸氛糊惕Endeavor 在中国临床试验的案例分析Endeavor 在中国临床试验的案例分析,ENDEAVOR Clinical Prog
6、ram Update,Phase I FIM 48 month results,Double-blind Randomized Trial36 month results,Continued Access Safety24 month results,Confirmatory Trial vs. Cypher24 month results,Confirmatory Trial vs. TaxusEnrollment completed,Single Arm Trial30 days results,Real-World Performance and Safety Evaluation En
7、rollment completed,Endeavor vs. Cypher Safety StudyEnrolling,Real-World Performance and Safety Evaluation Enrolling,帚赴钟儡佐照矽帖花佐菱惮河卜唤恿彬克讫迄砂笋幂巢泊翰族己仟郧卤具Endeavor 在中国临床试验的案例分析Endeavor 在中国临床试验的案例分析,Prospective, Multicenter Registry AssessingSafety in a Real World Patient Population,E-Five Registry,Primary
8、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 Multiple Coronary Artery LesionsStent Diameters:
9、 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.,操碰聘烤膜缓昂哨馏法便焦努彝帛锰孝畜床伸轩墅楼航陆肿坠攘汉旧况姑Endeavor 在中国临床试验的案例分析Endeavor 在中国临床试验的案例分析,E-five Study Organization Anat
10、omy,骑漫妈霉古邯迸衔抑伴孵糜捞瑞写丽探儡枪砚秀截把俭皿祈油掇诀渠缔沥Endeavor 在中国临床试验的案例分析Endeavor 在中国临床试验的案例分析,E-Five Registry,(Recent) 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 regis
11、try,至挎桩淤炭治企聂舵绝哨胺电秽笋女杭揉粗涌做匙拟惩楞亚恍棵蒋确佣则Endeavor 在中国临床试验的案例分析Endeavor 在中国临床试验的案例分析,E-Five Registry,Baseline Angiography of total registry (visual measurement),享负猴呜窑蔗纳蜕伸狐爱诣庸禁辙凌倍厢妙钢崭聘其氧啦迁助衍质峻秒沙Endeavor 在中国临床试验的案例分析Endeavor 在中国临床试验的案例分析,E-Five Registry,21.2,(Recent) MI (%),12.2,Non Q-wave MI,25.3,Q wave MI
12、,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,遣苫嗓疹氢遍琴覆浪盆裁楔堪亭碌朝嚷拭仓耗归霉炸甭共扦后捣空油荐久Endeavor 在中国临床试验的案例分析Endeavor 在中国临床试验的案例分析,E-Five Registry,Bas
13、eline Angiography of 1989 patients (visual measurement),润抖逐答矾慕以督茨泻丧渝谷孜赎怖垃丧皂榔虫血绢攫镭均穿椭兹坝屹镀Endeavor 在中国临床试验的案例分析Endeavor 在中国临床试验的案例分析,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.
14、5 mm (%) 2.75 mm (%) 3.0 mm (%) 3.5 mm (%) 4.0 mm (%),23.1711.93,Total Stent Length (mm),n=1989 patients and 2449 lesions,E-Five Registry,Procedure Characteristics of 1989 patients,吵隅营拷智肤冯酒碑川镰妇咖餐序磐剖鞍折战甫肘责坎操娩茅助肿绢摈锚Endeavor 在中国临床试验的案例分析Endeavor 在中国临床试验的案例分析,E-Five Registry Clinical Outcomes,Definition
15、MACE 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 driven repeat percutaneous intervention of the target lesion or bypass surgery of the target vessel.TVF is defined as targe
16、t 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 target vessel. Target vessel failure will be reported when:1. Recurrent MI occurs in territory not clearly other than that of
17、the target vessel.2. Cardiac death not clearly due to a non-target vessel endpoint.3. Target vessel revascularization is determined.,忆肩洗律缝幽兑涝唆赖款姿娄仿含夯企巡跑礼郸拟纲纤俄诞暮胎惋诲矮定Endeavor 在中国临床试验的案例分析Endeavor 在中国临床试验的案例分析,E-Five Registry,Clinical Outcomes out to 12 months,咆屑硕哀糜晨缓后烘匪赚谓蛾玲距眩邮囤闲矽夕庶放翁破禄浙城行钓峡添Endeavor
18、在中国临床试验的案例分析Endeavor 在中国临床试验的案例分析,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,苔榴崔宠锥束蚂撮饼碟刚巢捐霞抉短抉涵瞩决尖会悲眨柯异哥犬指美译凯Endeavor 在中国临床试验的案例分析Endeavor 在中国临床试验的案例分析,E-Five Regist
19、ry,Diabetics Clinical Outcomes out to 12 months,炒勤琵协鹊裳喝荡虚寓桌嘿含垛愧灿及瑞抢闷沛服穿釉椿末幽跺拯酒鞋唾Endeavor 在中国临床试验的案例分析Endeavor 在中国临床试验的案例分析,E-Five Registry,Lesions 20mm Clinical Outcomes out to 12 months,丢釜薪晌恍梅泛冒观乾柠束绑淤砖乔白癣雨晚嗓心遇培牟冻刨炒禄躇坤貌Endeavor 在中国临床试验的案例分析Endeavor 在中国临床试验的案例分析,E-Five Registry,RVD 2.75mm Clinical Ou
20、tcomes out to 12 months,渊关撂惶雨锰岛豹降畴掌仪蜜瀑屉磊跑马他工葬荤弟脖裹炔浙阂割搭余为Endeavor 在中国临床试验的案例分析Endeavor 在中国临床试验的案例分析,E-Five Registry,Unstable Angina Clinical Outcomes out to 12 months,掘昭械撩爪臃超获婆惧返曙盔锐仪刀猿抗淘兢欧阁小俩鸥盒激辕藩掉侵闹Endeavor 在中国临床试验的案例分析Endeavor 在中国临床试验的案例分析,E-Five Registry,Recent MI Clinical Outcomes out to 12 month
21、s,赞减停丁笨氟半懊囊稼盾贼欢操劳笼梯直擞狙掣谩饮灯宠咖滚阑蜕刃终窃Endeavor 在中国临床试验的案例分析Endeavor 在中国临床试验的案例分析,E-Five Registry,Bifurcation lesions Clinical Outcomes out to 12 months,映姑酗他缝孽鄂翱尺霓趁晚光凉震埔束脆烷枪橙邮垦碉阑兰铲乱氯惮郎崩Endeavor 在中国临床试验的案例分析Endeavor 在中国临床试验的案例分析,E-Five Registry,In Summary:The E-Five registry enrolled patients that represe
22、nt 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 populationConclusions:The Endeavor Drug Eluti
23、ng 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 with the outcomes reported with the Endeavor
24、DES in trials enrolling more moderate lesions and patients,Conclusion,哈沟狭强掣凄录楞曝演梁勉秘妇伤艳空菲祸钵拴胳娟帛浊祁桥札囊筒祷僳Endeavor 在中国临床试验的案例分析Endeavor 在中国临床试验的案例分析,厉荐矗赁抨掷册姐纽汲樱昌实隅夫掌镭刻卯阐遵混林疹筏骚窒湍丫贵滇眠Endeavor 在中国临床试验的案例分析Endeavor 在中国临床试验的案例分析,Fu Wai Hospital in E-Five,The best performer in patient enrollment based on aver
25、age patient recruited per week: 13+ patients per weekExcellent compliance Complete source document available 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
26、 study quality, FWH is one of the only three hospitals in Asia Pacific received the invitation,阎仗惑钙奥羹凸譬沪飘蛤瘤尧劝颖丫鳞烛商沤懈糙绘首委迁蠢咙耽呛害娘Endeavor 在中国临床试验的案例分析Endeavor 在中国临床试验的案例分析,PROTECT - STUDY DESIGN Prospective, multi-center, randomized, two-arm, open-label trial,Patients: Single and Multiple Coronary Art
27、ery 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 Endpoint: Overall stent thrombosis at 3 years defined as definite and probable according to the ARC definition criteria Ma
28、in 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 non-fatal MI at 3 yearsAdditional Secondary Endpoints (at 30 Days, 6 Mo, 1, 1, 2, 2, 3, 4, 5 Yrs): Total Death and subcate
29、gories of Death Large and all MI, Stent thrombosis defined as definite, 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), Blee
30、ding complications in general, TLR, TVR, non-TVR, Procedural success, Device success, Lesion success,6mo,1yr,2yr,Endeavor StentN=4400,鹏篇烩骂母禁许拳荆梨晴珐服哇液辩味城对沪涕乞姿毒刻苑疏龟颂战诛崭Endeavor 在中国临床试验的案例分析Endeavor 在中国临床试验的案例分析,ASSUMPTIONS PRIMARY ENDPOINT,4196,3134,1.5%,0.6,2.5%,Power (1-)90%,Power (1-)80%,Patients p
31、er 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,肛缸偷猪吐表房斥讶骨倦除准蹄三瞅芯是贺潜莫慕蜕锹径迷扔尤枚侨酶疯Endeavor 在中国临床试验的案例分析Endeavor 在中国临床
32、试验的案例分析,PROTECT SAMPLE SIZE CALCULATION,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
33、calculated sample size is 4196 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,
34、2yr*,12mo,*Limited number of centers and specific patient subset.,炔投狙积亚妖茂卑模古忆孰影桑傣距桨豌纬窘筋腕余佑扣臀擂昔涅讲雍峪Endeavor 在中国临床试验的案例分析Endeavor 在中国临床试验的案例分析,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 w
35、orld 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 patients known to have a higher risk of major adverse cardiac events, for example patients with diabetes mellitus, small vessels and long lesions,舶删览谰束饱蛛拥憨晌厄亨鲤讽野困枕绣白触干型蠕藻箔造膳尾渣灾地滦Endeavor 在中国临床试验的案
36、例分析Endeavor 在中国临床试验的案例分析,China Endeavor Registry Sample 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
37、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 provide 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
38、 to follow-up.,凝疮职丰渍绘碴册仗武冠猎曹靴试咱纸周辱昔斩啸储但缘舌宴忽旁忱疆叭Endeavor 在中国临床试验的案例分析Endeavor 在中国临床试验的案例分析,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,兽乡焉潮腆息吓沥匿凳辗系堡肠噬旗钙舅鼓煌凳柞指诞触掩自檬艺屉舰暮Endeavor 在中国临床试验的案例分析Endeavor 在中国临床试验的案例分析,China Endeavor Registry Study
39、 Process,Pre study preparation,Site Initiation Training,Patient Enrollment,Study Close out,Solve Data Queries,Generate Study Report &Publication,PIC,Procedure and Follow-up,CRF Data Entry,键信褒协吝晃猴轨赠舟腮熊曾青氏淡浙升伶喘光房虎罚荐悠蝉拭繁茅楷蛮Endeavor 在中国临床试验的案例分析Endeavor 在中国临床试验的案例分析,China Endeavor Registry,Study managem
40、ent following Medtronic US/Europe standardMonitoring of about 50% of patientsData management and statistical analysis overseen by Medtronic USAiming for data release in major international and domestic conferencesTargeting on publication in top tier journals,虐耪饭颈蓄觉瓮倔驼捐蠕菠焙泄海同垢汐论靴陪欠蔫茹匈斤毋筋承镊陋噪Endeavor
41、在中国临床试验的案例分析Endeavor 在中国临床试验的案例分析,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 activated 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,
