A prospective evaluation of the safety and efficacy of the TAXUS Element paclitaxel-eluting coronary stent system for the treatment of de novo coronary artery lesions: design and statistical methods of the PERSEUS clinical program

Abstract

Background: Paclitaxel-eluting stents decrease angiographic and clinical restenosis following percutaneous coronary intervention compared to bare metal stents. TAXUS Element is a third-generation paclitaxel-eluting stent which incorporates a novel, thinner-strut, platinum-enriched metal alloy platform. The stent is intended to have enhanced radiopacity and improved deliverability compared to other paclitaxel-eluting stents. The safety and efficacy of the TAXUS Element stent are being evaluated in the pivotal PERSEUS clinical trials.

Methods/design: The PERSEUS trials include two parallel studies of the TAXUS Element stent in single, de novo coronary atherosclerotic lesions. The PERSEUS Workhorse study is a prospective, randomized (3:1), single-blind, non-inferiority trial in subjects with lesion length < or = 28 mm and vessel diameter > or = 2.75 mm to < or = 4.0 mm which compares TAXUS Element to the TAXUS Express2 paclitaxel-eluting stent system. The Workhorse study employs a novel Bayesian statistical approach that uses prior information to limit the number of study subjects exposed to the investigational device and thus provide a safer and more efficient analysis of the TAXUS Element stent. PERSEUS Small Vessel is a prospective, single-arm, superiority trial in subjects with lesion length < or = 20 mm and vessel diameter > or = 2.25 mm to <2.75 mm that compares TAXUS Element with a matched historical bare metal Express stent control.

Discussion: The TAXUS PERSEUS clinical trial program uses a novel statistical approach to evaluate whether design and metal alloy iterations in the TAXUS Element stent platform provide comparable safety and improved procedural performance compared to the previous generation Express stent. PERSEUS trial enrollment is complete and primary endpoint data are expected in 2010. PERSEUS Workhorse and Small Vessel are registered at http://www.clinicaltrials.gov, identification numbers NCT00484315 and NCT00489541.

Figure 1

PERSEUS WH and PERSEUS SV Study Schematic.

Figure 2

Strength and flexibility of the TAXUS Element stent compared to TAXUS Express and TAXUS Liberté stents. (A) Stent integrity, as measured by an accelerated life test of the bending fatigue of a stent in a simulated overlapped stent configuration, showing number of bend cycles before stent fracture. The test is conducted by mounting one end of a nominally deployed stent to a fixed mandrel while the other end is mounted to a mandrel suspended in a flexible membrane. The membrane mounted end of the stent is translated perpendicular to the longitudinal axis of the stent to impart a repeatable bend in the stent. (B) Conformability - a measure of the torque required to bend the stent to a specific curvature, which is directly related to flexibility of the stent. Lower required bending moment indicates increased flexibility. N = 15 for each stent type. Bars represent ± 1 standard deviation.

Figure 3

(A) Express, Liberté, and Element stent architecture; (B) Radiographic comparison of Element and Express stents. Radiographic image was generated using a General Electric OEC 9800 Digital Imaging System at operating conditions of 51 kV and 11.66 mA. No anatomical simulating phantom was used during imaging.

Figure 4

Fibrin deposition around stent struts following TAXUS stent implantation in porcine coronary arteries. Swine coronary arteries were implanted with overlapping bare metal or TAXUS Express, TAXUS Liberté, or TAXUS Element paclitaxel-eluting stents and examined at 30, 90, and 180 days using light microscopy. Peristrut fibrin deposition was evaluated by study pathologists and scored on a 0-3 scale where 0 = no visible fibrin, 1 = mild fibrin present, 2 = moderate fibrin present, 3 = extensive fibrin present. Trichrome stained sections, 200× plate magnification. See Seifert et al., 2007 for more detailed methods [29]. (A) Example specimens at 180 days showing peristrut fibrin deposition histology. Number of specimens in each category is shown as n/N. (B) Number of specimens with extensive fibrin deposition (score 3) at each timepoint. There were no significant differences among control bare metal stents in any of the studies.