Novel Approaches for Preventing or Limiting Events (NAPLES III) Trial: Randomised Comparison of Bivalirudin Versus Unfractionated Heparin in Patients at High Risk of Bleeding Undergoing Elective Coronary Stenting Throught The Femoral Approach. Rationale and Design

Purpose Bivalirudin (Angiox, The Medicine's Company, Parsippany, NJ), a synthetic direct thrombin inhibitor, when compared with standard antithrombotic therapy (including unfractionated heparin [UFH] alone or plus a glycoprotein IIb/IIIa inhibitor) determines a significant decrease of major and minor bleeding and similar protection against ischemic events both in elective and in urgent percutaneous coronary intervention (PCI). There is a lack of prospective clinical trial assessing the safety and the efficacy of bivalirudin compared with UFH alone in the subset of biomarker negative patients at high risk of bleeding undergoing to elective PCI through the femoral approach. Methods This is a single-center, investigator-driven, randomized, double-blind, controlled trial (www.clinicaltrial.gov registration: NCT01465503). Consecutive patients at high bleeding risk (score >= 10 according to Nikolsky et al.) undergoing elective PCI through the femoral approach will be screened for eligibility. Included patients will be randomized (ratio 1.1) to bivalirudin (Bivalirudin group) and UFH (UFH group). The primary endpoint will be the rate of major bleeding (REPLACE 2 criteria). We expect a major bleeding rate >= 5 % in the UFH group versus a <= 3 % event rate in the Bivalirudin group. Aiming for a 0.05 alpha and 0.80 power, a total of 662 patients will be needed. This number will be increased by about 25 % (leading to a total of approximate to 830 patients) because of uncertainty about expected endpoint rates. Conclusions The present trial will give important information on what is the best anticoagulation regimen when performing PCI through the femoral approach in patients at high risk for bleeding.