ecallantide and Blood-Loss--Surgical

Ecallantide is a recombinant peptide in the same class as aprotinin that inhibits plasma kallikrein, a major component of the contact coagulation and inflammatory cascades. Therefore, ecallantide was expected to reduce blood loss associated with cardiac surgery requiring cardiopulmonary bypass.. This prospective multinational, randomized, double-blind trial enrolled patients undergoing cardiac surgery using cardiopulmonary bypass for procedures associated with a high risk of bleeding. Patients were randomly assigned to ecallantide (n = 109) or tranexamic acid (high dose, n = 24; low dose, n = 85). Efficacy was assessed from the volume of packed red blood cells administered within the first 12 hours after surgery.. The study was terminated early after the independent data safety and monitoring board observed a statistically significantly higher 30-day mortality in the ecallantide group (12%) than in the tranexamic acid groups (4%, P = .041). Patients receiving ecallantide received more packed red blood cells within 12 hours of surgery than tranexamic acid-treated patients: median = 900 mL (95% confidence interval, 600-1070) versus 300 mL (95% confidence interval, 0-523) (P < .001). Similar differences were seen at 24 hours and at discharge. Patients treated with the higher tranexamic acid dose received less packed red blood cells, 0 mL (95% confidence interval, 280-600), than the group treated with the lower dose, 400 mL (95% confidence interval, 0-400) (P = .008). No deaths occurred in the higher dose tranexamic acid group.. Ecallantide was less effective at reducing perioperative blood loss than tranexamic acid. High-dose tranexamic acid was more effective than the low dose in reducing blood loss.

Topics: Aged; Blood Loss, Surgical; Cardiac Surgical Procedures; Cardiopulmonary Bypass; Double-Blind Method; Early Termination of Clinical Trials; Erythrocyte Transfusion; Europe; Female; Hemostatics; Humans; Male; Middle Aged; Peptides; Postoperative Hemorrhage; Prospective Studies; Risk Assessment; Risk Factors; Time Factors; Tranexamic Acid; Treatment Outcome; United States

Plasma kallikrein plays a major role in the contact (kallikrein-kinin) cascade producing bradykinin. Bradykinin is a vasodilator, which increases vascular permeability, activates inflammation and produces pain. Plasma kallikrein is also crosslinked to the coagulation system and the complement cascade.. Ecallantide (DX-88) is a potent and specific inhibitor of plasma kallikrein. Ecallantide is a recombinantly produced and engineered small protein based on the first Kunitz domain of human tissue factor pathway inhibitor. It was identified through phage display technology.. The search terms 'ecallantide', 'DX-88' and 'hereditary angioedema' were entered into Pubmed/Medline, ClinicalTrials and Google.. At present, the drug is being studied for two major indications. First, the results for the treatment of hereditary angioedema are promising. Second, a prospective randomised multi-centre trial for the reduction of blood loss during on-pump cardiothoracic surgery will be terminated in October 2008.

Topics: Angioedemas, Hereditary; Blood Loss, Surgical; Cardiac Surgical Procedures; Clinical Trials as Topic; Humans; Kallikreins; Peptides; Serine Proteinase Inhibitors