SPIRIT IV trial design: A large-scale randomized comparison of everolimus-eluting stents and paclitaxel-eluting stents in patients with coronary artery disease

Abstract

In the 300-patient SPIRIT II and 1002-patient SPIRIT III randomized trials, the everolimus-eluting stent (EES) compared to the paclitaxel-eluting stent (PES) resulted in reduced angiographic late loss (a primary end point in both trials), noninferior rates of 9-month target vessel failure (a primary end point in SPIRIT III), and reduced rates of target lesion revascularization and major adverse cardiac events (secondary end points). However, neither trial was powered for superiority for clinical end points, and the routine performance of angiographic follow-up may have artificially exaggerated the absolute benefits of EES. The relative efficacy of these 2 stents in patients with diabetes mellitus also remains controversial. We therefore designed a large-scale randomized trial without angiographic follow-up to further assess the differences between these 2 stent platforms. SPIRIT IV is an ongoing prospective, active-controlled, single-blinded, multicenter clinical trial in which 3690 patients with native coronary artery disease have been randomized 2:1 to EES versus PES. Patients with up to 3 de novo native coronary artery lesions (maximum 2 lesions per epicardial vessel) with length <or=28 mm and reference vessel diameter >or=2.5 to <or=4.25 mm were enrolled at 66 US clinical sites. Clinical follow-up at 30, 180, and 270 days; 1 year; and then yearly for up to 5 years is underway. The primary end point is the rate of ischemia-driven target lesion failure at 1 year, a composite measure of safety and efficacy consisting of cardiac death, target vessel myocardial infarction, or ischemia-driven target lesion revascularization, with the trial powered for sequential noninferiority and superiority testing. SPIRIT IV is the largest randomized comparison of 2 DES with completed enrollment. The absence of routine angiographic follow-up will allow an accurate assessment of the absolute differences in the clinical safety and efficacy profile between these devices. The magnitude of the study will also permit significant insights to be gained into the relative performance of the 2 stents in important subgroups, including patients with diabetes mellitus.