Phase-III Trial Begins to Evaluate Angiomax in Patients Undergoing Peripheral Endovascular Procedures

October 9, 2013—The Medicines Company reported enrollment of the first patient in a phase-III clinical trial comparing the anticoagulant Angiomax (bivalirudin) to unfractionated heparin (UFH) in patients undergoing peripheral endovascular intervention (PEI). The trial’s Principal Investigator is Barry Katzen, MD, who is Founder and Medical Director of Baptist Cardiac and Vascular Institute in Miami, Florida.

According to the company, the ENDOMAX trial of endovascular interventions with Angiomax is a randomized, double-blind, clinical trial to study pharmacology in patients undergoing PEI, which is performed in approximately 500,000 patients in the United States each year. Angiomax is currently approved for use in patients undergoing percutaneous coronary intervention (PCI). The Medicines Company intends to pursue labeling expansion in the PEI setting.

In the company’s press release, Dr. Katzen commented, “ENDOMAX is examining clinical endpoints critical to improving outcomes in PEI patients, including bleeding, amputations, stroke, and mortality. Angiomax has been studied extensively in preventing clotting during PCI of the heart vasculature; however, ENDOMAX is a new opportunity to look at the similar procedures in the peripheral vasculature.”

According to The Medicines Company, the primary objective of the study is to demonstrate that anticoagulation with Angiomax results in fewer major bleeding complications (at 48 hours postprocedure) compared with UFH in patients undergoing PEI. The secondary objective is to identify the potential benefits of Angiomax therapy on other clinically important events such as death, myocardial infarction, stroke and/or transient ischemic attack, amputation, unplanned repeat revascularization, and minor bleeding, as well as potential economic benefits that may result from improved clinical outcomes.

The trial will compare Angiomax bolus and infusion to a bolus of UFH in a 1:1, double-blind, randomized design. The Medicines Company anticipates enrolling approximately 3,900 patients undergoing an endovascular procedure, such as carotid artery stenting or lower extremity intervention, including those for critical limb ischemia or claudication. The trial is statistically powered to determine whether Angiomax demonstrates superiority to heparin for a primary endpoint of bleeding assessed at 48 hours postprocedure. 

Secondary endpoints of death, myocardial infarction, stroke, amputation, and urgent revascularization will also be assessed at 30 days and 1 year. At 1-year, mortality and amputation data will be collected. Health economic outcomes including length of stay, time to sheath removal, and time to ambulation will be assessed. 

The Medicines Company advised that Angiomax for injection is a direct thrombin inhibitor with a naturally reversible mechanism of action and a 25-minute half-life. In the United States, Angiomax is indicated in patients undergoing PCI with provisional use of glycoprotein IIb/IIIa inhibitor and in patients with, or at risk of, heparin-induced thrombocytopenia and thrombosis syndrome undergoing PCI. In addition, Angiomax is indicated for use as an anticoagulant in patients with unstable angina undergoing percutaneous transluminal coronary angioplasty. Angiomax is intended for use with aspirin. Angiomax is not approved for use in patients with acute coronary syndromes who are not undergoing PCI or percutaneous transluminal coronary angioplasty.