spirit iii clinical trial of the xience v® everolimus eluting coronary stent system (eecss)

Conditions: Stents; Coronary Artery Disease; Total Coronary Occlusion; Coronary Artery Restenosis; Stent Thrombosis; Vascular Disease; Myocardial Ischemia; Coronary Artery Stenosis

Summary: this study is divided into 5 arms: 1. randomized clinical trial (rct): prospective, randomized, active-controlled, single blind, parallel two-arm multi-center clinical trial in the united states (us) comparing xience v® everolimus eluting coronary stent system (css) (2.5, 3.0, 3.5 mm diameter stents) to the food and drug administration (fda) approved commercially available active control taxus® express2™ paclitaxel eluting coronary stent (taxus® express2™ pecs) system 2. us 2.25 mm non-randomized arm using 2.25 mm diameter xience v® everolimus eluting css 3. us 4.0 mm non-randomized arm using 4.0 mm diameter xience v® everolimus eluting css 4. us 38 mm non-randomized arm using 38 mm in length xience v® everolimus eluting css 5. japanese non-randomized arm using xience v® everolimus eluting css (2.5, 3.0, 3.5, 4.0 mm diameter stents) in japan the taxus® express2™ paclitaxel eluting coronary stent system is manufactured by boston scientific.

the purpose of the spirit iii clinical trial is to evaluate the safety and efficacy of the xience v® everolimus eluting coronary stent system (xience v® eecss). the xience v® eecs (xience v® arm) will be compared to an active control group represented by the fda approved commercially available boston scientific taxus® express2™ paclitaxel-eluting coronary stent (taxus® express2™ pecs) system (taxus® arm). the spirit iii clinical trial consists of a randomized clinical trial (rct) in the us which will enroll approximately 1,002 subjects (2:1 randomization xience v® eecs : taxus® express2™ pecs) with a maximum of two de novo native coronary artery lesion treatment within vessel sizes \>= 2.5 mm and \<= 3.75 mm. the spirit iii clinical trial also consists of three concurrent us non-randomized arms (2.25 mm diameter stent, 4.0 mm diameter stent and 38 mm length stent arms) and one japanese non-randomized arm as follows: 1. 105 subjects with a maximum of two de novo native coronary artery lesion within vessel sizes \> 2.25 mm and \< 2.5 mm and lesion length \<= 22 mm will be enrolled concurrently in the us 2.25 mm non-randomized treatment arm 2. 80 subjects with a maximum of two de novo native coronary artery lesion within vessel sizes \> 3.75 mm and \>= 4.25 mm and lesion length \<= 28 mm will be enrolled concurrently in the us 4.0 mm non-randomized treatment arm 3. 105 subjects with a maximum of two de novo native coronary artery lesion within vessel sizes \> 3.0 mm and \ 24 mm and \< 32 mm will be enrolled concurrently in the us 38 mm non-randomized treatment arm. 4. 88 japanese subjects with a maximum of two de novo native coronary artery lesions within vessel sizes \>= 2.5 mm and \<= 4.25 mm and lesion length \<= 28 mm will be enrolled concurrently in the non-randomized japanese arm. all subjects in the rct and the four non-randomized arms will be screened per the protocol required inclusion/exclusion criteria. the data collected will be compared to data from the subjects enrolled into the taxus® arm of us rct. subjects enrolled in the us rct will be sub-grouped based on whether they will have an angiographic and/or an intravascular ultrasound (ivus) follow-up at 240 days as follows: group a: angiographic and ivus follow-up at 240 days (n=240) group b: angiographic follow-up at 240 days (n=324) group c: no angiographic or ivus follow-up (n=438) all subjects will have clinical follow-up at 30, 180, 240 and 270 days (data collected through 270 days will be submitted as the primary data set for us and japanese market approval), and 1, 2, 3, 4, and 5 years (for annual reports). all subjects enrolled into three us non-randomized arms (n=105 for 2.25 mm arm, n=80 for 4.0 mm arm and n=105 for 38 mm stent arm) will have clinical follow-up at 30, 180, 240, and 270 days, and angiographic follow-up at 240 days. no ivus follow-up is required for subjects enrolled in these arms. all subjects enrolled into the japanese non-randomized arm (n=88) will have clinical follow-up at 30, 180, 240, and 270 days, and angiographic and ivus follow-up at 240 days. all subjects who receive a bailout stent will be assigned to group a follow-up subgroup (angiographic and ivus follow-up at 240 days after the index procedure), regardless of their primary assignment at randomization. at sites without ivus capability, subjects receiving bailout stent will be assigned to group b follow-up subgroup (angiographic follow-up at 240 days after the index procedure). angiographic follow-up is required for all bailout subjects at 240 days. data from the us rct will be submitted to the fda as the primary data set for product approval for rvd \>= 2.5 mm and \ =2.5 mm and \ 2.25 mm and \ 3.75 mm and \ 3.0 mm and \ 24 mm and \<= 32 mm), respectively in the us. a pharmacokinetic substudy will be carried out in a minimum of 5 pre-determined sites in the us and a minimum of 5 pre-determined sites in japan. in the us, the pharmacokinetics (pk) of everolimus, as delivered by the xience v® eecs will be analyzed in a subset of 15 subjects (minimum) with single vessel/lesion treatment, and up to 20 subjects with dual vessel/lesion treatment, respectively. in japan, a minimum of 10 subjects with single vessel/lesion treatment and up to 20 subjects with dual vessel/lesion treatment will have a pk measurements performed. these subsets will include subjects receiving overlapping stents.

Eligibility criteria:
inclusion criteria: * target lesion(s) must be located in a native epicardial vessel with visually estimated diameter between \>= 2.25 mm and \<= 4.25 mm and a lesion length \<= 32 mm * the target lesion(s) must be in a major artery or branch with a visually estimated stenosis of \>= 50% and \ = 1 * non-study, percutaneous intervention for lesions in a non-target vessel is allowed if done \>= 90 days prior to the index procedure (subjects who received brachytherapy will be excluded from the trial) exclusion criteria: * located within an arterial or saphenous vein graft or distal to a diseased (vessel irregularity per angiogram and \> 20% stenosed lesion by visual estimation) arterial or saphenous vein graft * lesion involving a bifurcation \>= 2 mm in diameter or ostial lesion \> 50% stenosed by visual estimation or side branch requiring predilatation * located in a major epicardial vessel that has been previously treated with brachytherapy * located in a major epicardial vessel that has been previously treated with percutaneous intervention \< 9 months prior to index procedure * total occlusion (timi flow 0), prior to wire passing * the target vessel contains thrombus * another significant lesion (\> 40% diameter stenosis \[ds\]) is located in the same epicardial vessel as the target lesion

Keywords: everolimus