Endeavor在中国临床试验的案例分析学习教案

1、会计学1Endeavor在中国临床试验的案例分析在中国临床试验的案例分析第1页/共42页CRAs*/MonitorsRandomization SystemData Management & Statistical AnalysisCore LabsCEC*CRA: Clinical Research AssociateCEC: Clinical Event Committee第2页/共42页Pre study preparationSite Initiation TrainingPatient EnrollmentStudy Close outSolve Data QueriesGe

2、nerate Study Report &PublicationPICRandomizationProcedure and Follow-upCRF Data Entry第3页/共42页Phase I FIM 48 month resultsDouble-blind Randomized Trial36 month resultsContinued Access Safety24 month resultsConfirmatory Trial vs. Cypher24 month resultsConfirmatory Trial vs. TaxusEnrollment complet

3、edSingle 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 patients)ENDEAVOR III(436 patients)ENDEAVOR IV(1548 patients)ENDEAVOR Japan(99 pa

4、tients)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 resultsContinued Access Safety24 month resultsConfirmatory Trial vs. Cypher24 month

5、 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 Evaluation Enrolling第4页/共42页30d6mo2yr*12mo*Limited number of centers and spec

6、ific patient subset.第5页/共42页CRAs/MonitorsE-CRF SystemData Management & Statistical AnalysisCore LabsCEC第6页/共42页(Recent) MI (%)Non Q-wave MIQ wave MIPrior CABG (%)Unstable Angina (%)Diabetes Mellitus (%)Prior PCI (%)Prior MI (%)Age (years)Male Gender (%)n = 8318 Patients76.763.3011.0632.112.221.4

7、25.37.532.721.834.0第7页/共42页n=8318 patients and 10343 lesionsLAD (%)46.6B2/C Lesions (%)60.3RVD (mm)2.930.47Lesion Length (mm)18.5010.60Pre-procedure MLD (mm)0.500.41Pre-procedure DS (%)82.8413.51Post-procedure DS (%)2.418.24第8页/共42页21.2(Recent) MI (%)12.2Non Q-wave MI25.3Q wave MI7.0Prior CABG (%)31

8、.2Unstable Angina (%)34.4Diabetes Mellitus (%)23.9Prior PCI (%)35.9Prior MI (%)62.9511.46Age (years)76.9Male Gender (%)n = 1989 patients第9页/共42页n=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 (%)

9、81.9313.99Post-procedure DS (%)2.016.33第10页/共42页18.199.90Lesion Length (mm)1.350.53Stent: Lesion Length28.8Long 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 (%)23.1711.93Total Stent Length (mm)n=1

10、989 patients and 2449 lesions第11页/共42页第12页/共42页30 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) - % (n)1.4 (27)3.0 (57)Stent Thrombosis (all) - % (n)0.8 (1

11、6)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 months第13页/共42页Complex SubsetsSample size n=1989Diabetics - % (n) Ins

12、ulin 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 months第16页/共42页30 daysn=91312 monthsn=866Death (all) - % (n)1.1 (10)3.5 (30) Cardiac0.9 (8)2.5 (22)MI (all) - % (n)1.1 (10)2.0 (17) Q Wave0.2 (2)0.6 (5) N

13、on 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)TVR - % (n)0.7 (6)6.8 (59)MACE - % (n)2.2 (20)9.6 (83)TVF - % (n)2.0 (18

14、)9.2 (80)RVD 2.75mm Clinical Outcomes out to 12 months第17页/共42页30 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)Death (cardiac) + MI (all) - % (n)1.5 (9)2.4 (14)Stent Thrombosis (all) - % (n

15、)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 Outcomes out to 12 months第18页/共42页30 daysn=42112 monthsn=393Death (all) - % (n)2.

16、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)1.5 (6) 31-360days 00.3 (1)TLR - % (n)0.7 (3)2.0 (8)TVR (non-TL) - % (n)00.3 (1)T

17、VR - % (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 months第19页/共42页30 daysn=38412 monthsn=359Death (all) - % (n)1.0 (4)4.2 (15) Cardiac1.0 (4)3.3 (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 (ca

18、rdiac) + 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)MACE - % (n)2.1 (8)8.9 (32)TVF - % (n)2.1 (8)9.5 (34)Bifurcation lesions Clinical Outcomes

19、out to 12 months第20页/共42页第21页/共42页第22页/共42页第23页/共42页Patients: Single and Multiple Coronary Artery LesionsCypher StentN=44008,800 patients200 sitesClinical FUProcedure30d1yr2yrs3yrs4yrs5yrsAnti-platelet therapy for 312 months Primary endpoint at 3 yearsPrimary Endpoint: Overall stent thrombosis at 3

20、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 non-fatal MI at 3 yearsAdditional Second

21、ary 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 revascularization), Major Adverse Cardiac an

22、d Cerebral Events (MACCE)Stroke (hemorrhagic in nature while on clopidogrel), Bleeding complications in general, TLR, TVR, non-TVR, Procedural success, Device success, Lesion success 6mo1yr2yrEndeavor StentN=4400第24页/共42页419631341.5%0.62.5%Power (1- )90%Power (1- )80%Patients per arm ENDEAVORHR CYPH

23、ERThe 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第25页/共42页第26页/共42页CRAs*/MonitorsRandomization SystemE-CRF systemData Management & Statistical AnalysisCore LabsCRA: Clinical Research AssociateCEC: Clinical Event CommitteeCEC*第27页/共42页第28页/共42页第29页/共42页第30页/共42页 Cultivate research atmosphere