NCT01465503

Novel Approaches in Preventing and Limiting Events III Trial (NAPLES III): Bivalirudin in High-risk Bleeding Patients

Bivalirudin in Patient at High Risk of Bleeding Undergoing Percutaneous Coronary Interventions.

• Status: Completed
• Phase: Phase 3
• Study type: Interventional
• Enrollment: 837 (actual)
• Sponsor: Clinica Mediterranea · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

Bleeding occurring during percutaneous coronary interventions (PCI has now emerged as one of the most common complication of PCI and adversely affect in-hospital, short- and long-term outcome.As bivalirudin proved its effectiveness in decreasing haemorrhagic events during PCI, its administration may be advocated in subjects deemed at high risk of bleeding.Objective of the present trial is to compare the safety and effectiveness of procedural use of bivalirudin in comparison to unfractionated heparin (UFH) in patients undergoing PCI deemed at high risk of procedural bleeding.

Detailed description

Antithrombotic and antiplatelet therapies have been the focus of extensive clinical investigations over the past 2 decades. In PCI settings all therapies inhibiting coagulation and primary hemostasis may limit ischaemic event rates, but are associated with an increased risk of bleeding. Retrospective and registry data indicates that haemorrhage is associated with mortality in patients undergoing PCI, emphasizing the potential importance of minimizing bleeding, as well as ischemic events, bleeding has now emerged as one of the most common complication of PCI. Major bleeding and blood transfusion have been strongly associated with increased rates of in-hospital and late mortality, MI and repeat revascularization after PCI. Also minor bleeding, although represent a complication significantly less dangerous than major haemorrhages, are associated with prolonged hospitalization, increased cost and adversely affect short- and long-term outcome. UFH is the most commonly used anticoagulant drug during PCI. Bleeding events during PCI may be in part due to the use of this drug. Bivalirudin (The Medicine's Co., Parsippany, NJ) is a synthetic direct thrombin inhibitor approved for patients with stable and unstable coronary syndromes undergoing PCI. Favourable properties of bivalirudin may minimize bleeding. Several clinical and procedural factors have been evaluated to identify patients exposed to a higher risk of hemorrhages. Nikolsky et al. have developed a risk score (validated on REPLACE-1 and REPLACE-2 data) based on clinical variable useful to predict the incidence of major peri-procedural bleeding after contemporary PCI using the femoral approach. The clinical variables considered into this algorithm are age \>55 years (integer score 4 for every 10 years over 55), female gender (integer score 3), eGFR \<60 ml/min/1.73 m2 (integer score 2), pre-existing anaemia (integer score 2), and administration of low-molecular weight heparin within 48 hours (integer score 2). Global risk score 0-1 anticipated a major bleeding rate of 1.3%; a risk score 2-6 was associated with a 1.8% risk of major bleeding; a risk score 7-9 associated with a 2.7% risk if major bleeding, whereas a risk score \>=10 was associated with a 5% rate of major bleeding. Our hypothesis is that bivalirudin, compared with UFH, may provide significant benefits in term of bleeding in the selected population of patients deemed at high risk of bleeding. Our aim is thus to prove, in a double-centres, randomized, blind controlled trial enrolling patients undergoing PCI via the femoral approach, the efficacy in term of haemorrhagic events and, secondarily, the effectiveness and safety of bivalirudin by means of the study drug vs UFH. Sample size estimation: in this high risk population we expect a rate of major and minor bleeding of \>5% for the UFH group vs a 3% event rate in the bivalirudin group. Aiming for a 0.05 alpha and 0.80 power, a total of 662 patients will need to be enrolled (331 patients per group). This will be increased by about 25% (leading to a total of 830 patients) because of considerable uncertainty about expected end-point rates.

Conditions

• Bleeding

Interventions

Type	Name	Description
DRUG	Bivalirudin	Patients randomized to Bivalirudin group will be treated by bivalirudin before and during the procedure. Bivalirudin will be given as bolus of 0.75 mg/kg prior to the start of the intervention, followed by infusion of 1.75 mg/kg per hour for the duration of the procedure.The infusion will be lowered to 1.0 mg/kg per hour in patients with eGFR \<30 ml/min/1.73 m2.
DRUG	Unfractionated Heparin	Patients randomized to the Control group will receive unfractionated heparn (UFH) before and during the procedure. UFH bolus will be of 70 UI/kg. If the activated clotting time measured 5 minutes after the study drug administration is lower than 270 seconds, an additional bolus of the randomised drug (UFH 20 U/kg) will be given.

Timeline

• Start date: 2008-01-01
• Primary completion: 2012-12-01
• Completion: 2013-12-01
• First posted: 2011-11-04
• Last updated: 2014-04-08

Locations

2 sites across 1 country: Italy