General Report on Clinical Trial of. Sirolimus-eluting Coronary Stent System

Transcription

1 General Report on Clinical Trial of AFFINITY Sirolimus-eluting Coronary Stent System PRODUCT NAME: Sirolimus-eluting Coronary Stent System TRADE NAME: AFFINITY Sirolimus-eluting Coronary Stent System SPECIFICATION: Diameter mm, length mm EXECUTANT: Umbra Medical Corp. Inverness, Florida USA MEDICAL 1. Beijing Anzhen of the Capital INSTITUTIONS University of Medical Sciences RESPONSIBLE 2. Xijing of the Fourth Military Medical FOR THE University CLINICAL TRIAL: 3. Gansu Province People TYPE OF THE Clinical Validation CLINICAL TRIAL: DATE:

2 Declaration 1. The medical institution that responsible for clinical trial should perform clinical trial and fill in the report impartially and objectively with a serious and responsible attitude. 2. The type of this clinical trial is clinical validation. 2

3 1. Test method and analysis method of the clinical trial ⑴ Objective: The objective of this clinical trial was to validate the safety and efficacy of sirolimuseluting coronary stent system produced by Umbra Medical Corp. in the treatment of coronary artery disease. ⑵Test method: According to the requirement in clinical proposal, the trial was designed as a multicentered clinical study. A total of 35 patients were involved in the study. Percutaneous coronary intervention (PCI) was performed and the patients were followedup for 30 days, 3 months and 6 months. A second angiography was performed in nearly 19 patients 6 months later. The primary endpoint in this study was target vessel failure (TVF), which was defined as revascularization in target vessel, recurrent myocardial infarction, or cardiac death that can not be excluded from target vessel origin within 6 months. Secondary endpoint: main adverse cardiac event (MACE), including death, myocardial infarction (Q wave and non-q wave), acute coronary artery bypass or target lesion revascularization within 6 months after the surgery, binary angiographic restenosis 6 months after treatment ( 50% diameter stenosis), minimum lumen diameter (MLD) in the stent and segment 6 months after treatment, target lesion revascularization (TLR) 6 months after treatment, and target vessel revascularization (TVR) 6 months after treatment. Attainment of final diameter stenosis <50% and no death, myocardial infarction or target vessel revascularization by means of percutaneous intervention means that the treatment was successful. ⑶Statistical method Synthetic performance of the drug stent was examined from three aspects in the clinical trial, including its performance during surgery, quality of life (safety) of the patients after implantation during hospital stay and post-discharge and therapeutic effect (efficacy) during the observation period. Summary description on qualitative data was expressed with frequency and percentage, while summary description on continuous data was expressed with observation number, mean value and standard deviation. Control group: In the present study, history information about the clinical trial on Cypher 3

4 drug stent was used for control analysis. T test was performed on statistical data using SPSS software so as to determine whether significant difference existed between the population mean value and certain specified value of a variable. Mean value of the data from the clinical trial on Cypher drug stent was specified value for T test in the present study. Null hypothesis (H 0 ) of one sample T test assumed that there was no significant difference between population mean value and specified test value. T distribution associated probability value was calculated using SPSS software. If the associated probability value was smaller than or equal to significance value 0.05, H 0 was rejected, and it was considered that there was significant difference between population mean value and control value. On the contrary, if the associated probability value was bigger than significance value 0.05, H 0 was accepted, and it was considered that there was no significant difference between population mean value and control value. 2. Contents of the clinical evaluation Sirolimus-eluting coronary stent system was evaluated from three aspects in the clinical trial, including clinical application performance, postoperative safety and efficacy. Evaluations on clinical application performance included pushability, crossability through diseased region, covering ability, supporting force, and withdraw performance. The above evaluations were ranked as excellent, good, general, and poor according to the influence on degree of smoothness during surgery. Safety evaluations were consisted of statistical analysis on ratio of main cardiac events and complications. Adverse events included death, myocardial infarction (Q wave and non-q wave), acute bypass surgery, revascularization of target lesion 6 months after surgery, binary restenosis rate in angiography, and revascularization of target vessel 6 months after surgery. Main complications included stent thrombus, subacute thrombus, advanced stage thrombus, and cerebrovascular event. Efficacy evaluations were consisted of statistical analysis on surgery success rate, no cardiac event rate 6 months after surgery, no in-stent restenosis rate 6 months after surgery, vascular diameter of target lesion 6 months after surgery, and vascular lumen loss of target lesion 6 months after surgery. At last, efficacy after drug stent implantation was synthetically evaluated. 3. Results of the clinical trial ⑴Basic information of patients and stent 3

5 An sirolimus-eluting coronary stent system produced by Umbra Medical Corp., which was AFFINITY sirolimus-eluting stent, was implanted into each diseased region. Basic information of patients: 33 males and 2 females aged years old and averaged 55 years old. Total number of clinical cases: 35 patients who were involved in 6 months ±2 weeks follow-up, and among them 19 patients underwent a second coronary arteriongraphy after 6 months± 2 weeks. Disease condition of the patients: 17% myocardial infarction (MI), 20% hypertension, 3% hyperlipoidemia, average ejection fraction of 65%, 28% grade III or IV, 39% application of GPIIb/IIIa inhibitor, 40% left anterior descending coronary artery (LAD) implantation, 28% left circumflex coronary artery (LCX) implantation, 34% right coronary artery (RCA ) implantation, average reference vascular diameter (RVD) of 3.06mm, and average diameter stenosis (DS) of 87%. Detailed information of the patients was shown in table 1. ⑵Data of clinical trial The results of clinical trial on sirolimus-eluting coronary stent system were shown in table 2-table 4. Table 2 was evaluation table of clinical application performance, which recorded evaluations from the patients on application of stent in each surgery. Table 3 was a survey table of follow-up 6 months±15 days after surgery. Table 4 was statistical analysis on angiography 6 months±15 days after surgery. Cases of drop out and their reasons were listed in: There was no drop out. 4. Adverse events and side effects found in the clinical trial and treatment There was no adverse event or side effect during surgery and 6 months follow-up after surgery. 5. Efficacy analysis of the clinical trial (1) Clinical application performance Clinical trial of drug stent began from the s evaluation on its application performance during surgery, which included pushability, crossability through diseased region, covering ability, supporting force, and withdraw performance. The above 4

6 evaluations were ranked as excellent, good, general, and poor according to the influence of product on degree of smoothness during surgery. Statistical analysis was shown in table 5. Table 5 showed that sirolimus-eluting coronary stent system had good overall application performance (pushability, crossability through diseased region, covering ability, supporting force, and withdraw performance). Overall excellent rate was 92%, good rate was 7.4%, and there was no general or poor, which can meet the requirements of clinical application. ⑵Safety evaluation Safety evaluations were consisted of statistical analysis on rate of various endpoints (adverse cardiac events) and complications that occurred during observation period, so as to evaluate quality of life after surgery. The incidence of various adverse events that occurred during hospital stay, 1, 3, and 6 months observation period was summarized in table 6. Incidence of hospitalization, various adverse cardiac events and complications during follow-up observation period was summarized in table 7. Data from three famous clinical trials (TIM, RAVEL and SIRIUS) of Cypher drug stent, which were organized by Johnson & Johnson CORDIS company, were listed behind as control. Contrast analysis on the results in table 7 showed that sirolimus-eluting coronary stent system produced by Umbra Medical did not cause thrombosis when being implanted and there was no cardiac event during hospital stay or follow-up period. The results of hospital stay and follow-up showed that incidence of both main adverse cardiac events (MACE) and main complications was 0. Its safety had attained the level of similar products from abroad, compared with marketed Cypher drug stent. ⑶Efficacy evaluation on the clinical trial Data of efficacy evaluation on drug stent mainly came from the morphological results of a second angiography 6 months after surgery and were consisted of statistical analysis on surgery success rate, no cardiac event rate within 6 months after surgery, binary restenosis rate, target vessel diameter 6 months after surgery, and target vessel lumen loss 6 months after surgery, etc. Statistical data on efficacy of sirolimus-eluting coronary stent system produced by Umbra Medical Corp. in 35 PCI clinical tests were summarized in table 8. The success rate of 35 surgeries was 100%. The data of postoperative follow-up suggested that no adverse event rate was 100% during hospital stay and post-discharge. 6-months follow-up indicated that binary restenosis rate was 0%, in-stent lumen loss was only-0.01±0.168mm, and in-lesion lumen loss was 0.03±0.141mm. 5

7 The above efficacy data and data from the clinical trial on Cypher drug stent (RAVEL trial and SIRIUS trial) were listed in table 9 for comparison purpose. In-stent lumen loss was -0.01±0.16. Compared with that in Cypher RAVEL trial, which was -0.01±0.33, the associated P value was 0.71 (>0.05), indicating no significant difference. Compared with Cypher SIRIUS trial, which was 0.17±0.44,the associated P value was (<0.05), indicating a significant difference. In-lesion lumen loss was 0.03±0.14. Compared with that in Cypher RAVEL trial, which was 1.1±2.5, the associated P value was (<0.05), indicating a significant difference. Compared with that in Cypher SIRIUS trial, which was 0.24±0.47, the associated P value was (<0.05), indicating a significant difference. Most efficacy indices of sirolimus-eluting stent system produced by Umbra Medical had advantages over those found in RAVEL trial and SIRIUS trial of Cypher drug stent, a marketed product, suggesting that it had similar material, structure, function and application method with that of Cypher drug stent, offered similar good therapeutic effect and had reached the level of same kind of products from abroad. Predicted objectives of the present clinical validation had been obtained. 6. Conclusion of the clinical trial Clinical trial and validation on coronary artery stenting had been performed in 35 patients. Excellent rate in application performance of sirolimus-eluting coronary stent system produced by Umbra Medical Corp. was averagely 92% while good rate was averagely 7.4%, and there was no general or poor condition, indicating that it can meet the requirements of clinical application. The results of hospital stay and follow-up showed that incidence of main adverse cardiac events (MACE) was 0, incidence of main complications was 0, surgery success rate was 100%, and binary restenosis rate was 0%. In-stent lumen loss was -0.01±0.16 and in-lesion lumen loss was 0.03±0.14, having no statistical difference compared with marketed Cypher drug stent. In summary, the safety and efficacy of sirolimus-eluting coronary stent system produced by Umbra Medical Corp. had reached the level of same kind product from abroad. 7. Indications, applicability, contraindications, and announcements 7.1 Indications (1) Acute vascular occlusion and almost vascular occlusion in percutaneous coronary intervention; (2) Localized stenosis with reference vessel diameter larger than 2.5mm and primary 6

8 stent implantation aiming at reducing restenosis; (3) Obvious vessel dissection and (or) laceration; (4) Restenosis after percutaneous coronary intervention (PCI); (5) Significant residual stenosis after simple balloon dilation (>30%); (6) Acute coronary artery syndrome associated diseases 2. Applicability It was applicable to coronary artery disease that treated with percutaneous coronary intervention (PCI) in order to improve blood flow and reduce in-stent restenosis. 3. Contraindication Use of the AFFINITY Stent is contraindicated in the following patient types: Patients with a hypersensitivity to sirolimus or its structurally related compounds. Patients with a known hypersensitivity to polymethacrylates or polyolefn copolymers. Coronary artery Stenting is contraindicated for use in: Patients in whom antiplatelet and/or anticoagulation therapy is contraindicated. Patients judged to have a lesion that prevents complete inflation of an angioplasty balloon or proper placement of the Stent or delivery catheter 4. Announcements (1) The product was disposable; (2) The product was sterile and free of pyrogens. Use was forbidden if the package was found damaged; (3) The product must be used within the expiry date; (4) It was required to understand the usage and function of the product so as to ensure efficacy and safety. (5) The product must be operated by professional medical staff. (6) The product must be stored in a shady, dry, clean, and drafty place that be free of active gases and with relative humidity of less than 70% and temperature of lower than 30%. 8. Problems and suggestions The body size of specification on overwrap was too small and not clear enough so that not easy to be identified during surgery. The paper for overwrap was thin and therefore easy to be folded. It was suggested that the packing and printing should be improved in scale production. 7

9 9. Participants in clinical trial Clinical hospital Anzhen Anzhen Anzhen Anzhen Anzhen Anzhen Anzhen Anzhen Anzhen Xijing Xijing Xijing Xijing Xijing Xijing Personnel involved in clinical trial Lv Shuzheng Chen Yundai Ge Changjiang Wu Xiaofan Song Jiutao Lin Yuan Yuan Fei Chen Xin Jin Zeyu Lu Anlin Wang Haichang Li Weijie Li Chengxiang Guo Wenyi Dai Zhengxue Duty Department director Deputy department director Department director Deputy department director Professional title Professor Associate professor Associate chief Chief Associate chief Associate chief Associate chief Associate chief Department Clinical hospital Xijing Xijing Gansu Gansu Personnel involved in clinical trial Cheng Hexiang Yuan Yuan Xu Yixian Yang Zheng Duty Department director Professional title Associate chief Associate chief Associate chief Department 8

10 Gansu Gansu Gansu Gansu Gansu Gansu Zheng Yunyan Jiao Jian Gao Fentang Wang Xiaohuan Zhu Hongmei Gao Qiaozhen primary nurse Nurse-in-charge 9

11 Table 1 AFFINITY Sirolimus-eluting Stent Basic Information About the Clinical Cases No Patient name Chen Guqiang Yin Zhongqiu Qiao Jianzhong age gender Clinical diagnosis Specification 48 Male CAD, UAP, EH3 Grade Male CAD, UAP Male CAD, EAP He Yingxi 53 Male CAD Liu Yongfa 54 Male CAD, AMI Shen Qing 62 Male CAD, UAP Hai Decun 59 Male CAD, OMI, hyperlipoidemia Gu Xiang 52 Male CAD, OMI, EH3 Grade Ren Yongli Chen Yuhai Lu Huanliang Song Xiaojun Zhang Weijie Zhang Weijie 67 Male CAD, OMI, EH Male CAD,EAP Male 42 Male 65 Male 65 Male 15 Chang Jun 36 Male 16 Chang Jun 36 Male 17 Niu Xinhua 34 Male, grade 2 hypertension, grade 2 hypertension

12 No Patient name Xie Xinmao Wang Zhizhong Wang Zhizhong Li Yaorong Wang Fuxiang Yang Qingwen Jin Anquan Chen Xingren Mao Bingcheng age gender Clinical diagnosis Specification 53 Male 61 Male 61 Male 49 Male 86 Male 69 Male 40 Male 48 Male 56 Male 27 Zi Landi 42 Male 28 Wang Peihua 57 Female 29 Zi Landi 42 Male 30 Tian Liqiang 54 Male 31 Wu Yimin 72 Female 32 Zhao Hong 65 Male 33 Pu Haoran 50 Male Lu Changan Huang Jishou 73 Male, grade 3 hypertension Coronary artery disease, old inferior wall myocardial infarction, primary hypertension Coronary artery disease, old inferior wall myocardial infarction Male Coronary artery disease,stable

13 Poor General Good Excellent Poor General Good Excellent Poor General Good Excellent Poor General Good Excellent Poor General Good Excellent No. Pushability Crossability through diseased region Table2 AFFINITY Sirolimus-eluting Stent Evaluation Table of Clinical Application Performance Covering ability Supporting force Withdraw performance

14 Table 3 AFFINITY Sirolimus-eluting Stent Statistical Table of Clinical Follow-up 30 days after surgery 3 months after surgery 6 months after surgery Serial number Death al Myocardi n ss infarctio Acute bypa surgery on Target lesi ation Revasculariz sel Target ves ation Revasculariz Death al Myocardi ss infarction Acute bypa surgery on Target lesi ation Revasculariz sel Target ves ation Revasculariz Death al Myocardi n ss infarctio Acute bypa surgery on Target lesi ation Revasculariz sel Target ves ation Revasculariz hy Angiograp s restenosi

15 30 days after surgery 3 months after surgery 6 months after surgery Serial number Death al Myocardi n ss infarctio Acute bypa surgery on Target lesi ation Revasculariz sel Target ves ation Revasculariz Death al Myocardi ss infarction Acute bypa surgery on Target lesi ation Revasculariz sel Target ves ation Revasculariz Death al Myocardi n ss infarctio Acute bypa surgery on Target lesi ation Revasculariz sel Target ves ation Revasculariz hy Angiograp s restenosi

16 Table 4 AFFINITY Sirolimus-eluting Stent _Statistical Table of Angiography Data Before implantation After implantation 6-month angiography Item Reference In-stent In-stent lumen In-stent minimum In-lesion minimum minimum In-lesion minimum In-lesion lumen Lumen lumen diameter lumen diameter lumen diameter lumen lumen diameter diameter loss stenosis(%) diameter loss Serial (RLD) (MLD) (mm) (MLD) (mm) diameter (MLD) (mm) (mm) (mm) number (mm) (MLD) (mm)

17 Before implantation After implantation 6-month angiography Item Reference In-stent In-stent lumen In-stent minimum In-lesion minimum minimum In-lesion minimum In-lesion lumen Lumen lumen diameter lumen diameter lumen diameter lumen lumen diameter diameter loss stenosis(%) diameter loss Serial (RLD) (MLD) (mm) (MLD) (mm) diameter (MLD) (mm) (mm) (mm) number (mm) (MLD) (mm)

18 Table 5 AFFINITY Sirolimus-eluting Stent Statistical Table of Application Performance Items Performance Excellent (%) Good (%) General (%) Poor (%) Pushability 89% 11% 0 0 Crossability through diseased region 91% 9% 0 0 Covering ability 100% Supporting force 94% 6% 0 0 Withdraw performance 91% 9% 0 0

19 Table 6 AFFINITY Sirolimus-eluting Stent Evaluation Table of Clinical Safety Items Time Duration of hospital stay 30 days after surgery 3 months after surgery 6 months after surgery Incidence of adverse cardiac events Death Myocardial infarction Acute bypass surgery Target lesion Revascularization Target vessel Revascularization Subacute obstruction Incidence of thrombus at implantation Incidence of 6 month advanced stage thrombus Incidence of 6 month cerebrovascular events Main hemorrhage complications

20 Item Time Incidence of main cardiac adverse events Table 7 Statistical Table of Clinical Safety of Intravascular Drug (Sirolimus)-eluting Stent System AFFINITY Duration of stay AFFINITY 6 months after surgery Cypher FIM Trial hospital - ization Cypher FIM Trial return visit Cypher RAVEL Trial hospital - ization Cypher RAVEL Trial return visit Cypher SIRIUS Trial hospital - ization Cypher SIRIUS Trial return visit % 3.3% 2.5% 7.5% 2.4% 6.0% Death % % 0.2% 1.1% Myocardial infarction % 0 2.5% 1.7% 2.3% 0.8% Acute bypass surgery Target lesion Revascularizat % 0 2.5% 0.2% 4.7% ion Target vessel Revascularizat ion % 3.3% 0.8% % complication % 3.3% 0 1.6% 0.2% 5.1% Subacute obstruction Incidence of stent thrombus Incidence of advanced stage thrombus Incidence of cerebrovascul ar event Main hemorrhage complications % % % % 3.3% 0 0.8% 0.2% 0.9% % 3.6%

21 Table 8 AFFINITY Sirolimus-eluting Stent Evaluation Table of Clinical Efficacy Item Statistical Data remarks Surgery success rate 100% In-stent minimum lumen diameter (MLD) after implantation In stent diameter stenosis (DS%) after implantation In-lesion minimum lumen diameter (MLD) after implantation In-lesion diameter stenosis (DS%) after implantation 6 month in-stent minimum lumen diameter (MLD) 6 month in stent diameter stenosis (DS%) 6 month in-stent lumen loss (mm) 6 month in-lesion minimum lumen diameter (MLD) 6 month in-lesion lumen diameter stenosis (DS%) 6 month in-lesion lumen loss (mm) 2.8±0.3 (7.7±0.05)% 2.76±0.29 (9.78±3.2)% 2.89±0.35 (4.3±4.1)% -0.01± ±0.33 (11.5±5.2) % 0.03±0.141 Duality retenosis rate 0 6 month No-TLR rate 100% 6 month No-TVR 100% 6 month No-MACE 100% 1. Surgery success rate: (number of successful surgeries/total cases) 100% 2. MLD: Minimum lumen diameter 3. DS%: (1-MLD/RLD) 100%, RLD: Reference lumen diameter 4. 6 month lumen loss: MLD value at implatation-6 month MLD value 5. Duality retenosis rate: n1/n 100%, n1: number of cases with 6 month DS% that exceeded 50%, n: total cases.

22 Table 9 Evaluation Table on Clinical Efficacy of Sirolimus-eluting Stent System Item Trial Clinical trial on AFFINITY DES Clinical trial on Cypher RAVEL Cypher SIRIUS Clinical trial Surgery success rate 100% 96.7% 97.9% In-stent minimum lumen diameter (MLD) after implantation In stent diameter stenosis (DS%) after implantation In-lesion minimum lumen diameter (MLD) after implantation In-lesion diameter stenosis (DS%) after implantation 6 month in-stent minimum lumen diameter (MLD) 2.8± ± ±0.4 (7.7±0.05)% (11.9±5.9)% (5.4±8.2)% 2.76± ± ±0.45 (9.78±3.2)% (24.5±8.6) % (16.1±9.7)% 2.89± ± ± month in stent diameter stenosis (4.3±4.1)% (14.7±6.9)% (10.4±16.5)% (DS%) 6 month in-stent lumen loss (mm) -0.01± ± ± month in-lesion minimum lumen diameter (MLD) 6 month in-lesion lumen diameter stenosis (DS%) 6 month in-lesion lumen loss (mm) 2.73± ± ±0.61 (11.5±5.2) % (25.3±9.6) % (23.6±16.4) % 0.03± ± ±0.47 Duality retenosis rate % 6 month No-TLR rate 100% 97.4% 15% 6 month No-TVR 100% 96.6% 92.7% 6 month No-MACE 100% 89.9% 91.7%

23 Attachment Explanation of Problems Related with the Proposed Clinical Trial 1. Rationale for proposal of the clinical trial The material, structure, drug, function and application of drug stent produced by Umbra Medical were similar with those of Sirolimus Cypher drug stent from Johnson & Johnson CORDIS company. The present clinical trial on drug stent was a clinical validation. The proposal was established according to that of the clinical trial on Cypher drug stent organized by CORDIS company in aspects including methods, endpoint, observation period, study population, drug treatment, indications and contraindications. The proposal of this clinical trial complied with the requirements in Specification for clinical trial on medical equipment, and it was similar with the clinical trial on Cypher drug stent in objective, methods, endpoint, study population, drug treatment, main indications and contraindications. 2. Set up of control group In the present clinical trial, the clinical trial on Cypher drug stent was used as control group for the purpose of comparison. The present clinical trial did not use naked stent made of same kind metal as control, since Cypher drug stent had been marketed for 3 years and lots of clinical practices had demonstrated that drug stent was better than naked metal stent for general indications of coronary artery stenting. Common naked stent made of stainless steel had been substituted on current market, therefore using it as control had no clinical significance. In addition, performing clinical trial with substituted product did not comply with ethic norms. The data of clinical trial on Cypher drug stent had been completely published by U.S Food and Drug Administration and the information was relatively complete. Therefore, it was not necessary to repeat the study on Cypher drug stent and history information about it was used as control. 3. Study population and experimental baseline A same experimental baseline with the data of control group was the prerequisite for valid comparison with Cypher drug stent. Therefore, the clinical trial on Cypher drug stent organized by CORDIS company was taken as reference of the proposal in aspects including methods, endpoint, observation period, study population, drug treatment, indications and contraindications. Johnson & Johnson CORDIS company had organized three clinical trials before and after the

24 marketing of Cypher drug stent. The first clinical trial was the first investigation on drug stent in human beings (FIM trial) and of extremely high risk. It was only performed in 30 patients in two clinical centers in Holland and Spain. It was only limited to vessel diameter of mm and single stent length of 18mm and belonged to feasibility study. The second one was RAVEL trial that performed in 19 clinical centers in European and Latin America. 238 patients with in-situ coronary artery lesion were included (lesion length <18mm, diameter mm) and observed by angiography for 6 months. This clinical trial belonged to safety and efficacy study. The third one was SIRIUS trial in which the extent of clinical indications was extended. The trial was extended to more complicated long lesion, small vessel lesion, diabetic, multi-branch lesion. Furthermore, the stent was extended to coverage of mm and length of 8-33mm. The present clinical trial aimed to screen study cases on the basis of safe and effective indications as well as contraindications that demonstrated in three clinical trials on Cypher drug stent. Therefore, specified study population in the proposal of this clinical trial was: Patients with in-situ coronary artery lesion whose stenosis was 70%. Only 1 stent was implanted into each lesion. Stent length was 12-36mm and diameter was 2.5mm-4.0mm (ocular estimate). 4. Selection of number of cases for statistical analysis The present clinical trial was different in nature, compared with RAVEL trial and SIRIUS trial. The clinical trial on Cypher drug stent was an innovative and high risk clinical trial that belonged to need to be performed in large-scale. Sirolimus-eluting stent system produced by Umbra Medical was an imitation of Cypher drug stent and its clinical trial belonged to validation study. From the perspective of statistics, analysis on observation data from approximately 30 cases by commonly used SPSS software was enough to possess statistical significance. For the above reasons, three clinical centers and Umbra Medical considered that clinical validation on cases can obtain the objective of this clinical trial. 5. Observation period of the clinical trial Observation period of the clinical trial was 6 months, which was consistent with RAVEL clinical trial that performed before the registration of Cypher drug stent. Main basis for the establishment of clinical observation period: The main reasons for intravascular restenosis after implantation of coronary artery stent were unavoidable injury to inner vessel wall and physiological reaction of human body to metallic foreign body during implantation. The latter stimulated the proliferation of smooth muscle cells on inner vessel wall and platelet aggregation to repair injured inner vessel wall and enclose the metal stent. This process usually lasted for 3 months and led to a second vascular stenosis especially in the first month. Effective drug release from the stent was

25 concentrated in the first month after implantation, which was almost 0 three months later. 6 Selection of statistical analysis method The data from clinical trial on Cypher drug stent indicated a normal distribution, so that it can be treated with normal distribution hypothesis. It was known that statistical test of normal distribution offered statistical significance to the analysis result of small sample data. Therefore, statistical analysis on the data of this clinical trial was performed using differential t-test. Since the control group was known data of the clinical trial on Cypher drug stent, it was one sample t test. Specified test value was mean value of data of the clinical trial on Cypher drug sten. Commonly used SPSS software in domestic and foreign clinical trials was chosen. Statistical analysis on the results of the clinical trial was performed in the form of table. Summary description on qualitative data was expressed with frequency and percentage. Summary description on quantitative data was expressed with observation number, mean value, and standard deviation. General Director of the project: Lǚ Shuzheng 02/07/2005