title: A phase 2 prospective, randomized, double-blind trial comparing the effects of tranexamic acid with ecallantide on blood loss from high-risk cardiac surgery with cardiopulmonary bypass (CONSERV-2 Trial).
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors: Cubist Pharmaceuticals, Inc. 65 Hayden Avenue, Lexington, MA 02421, USA. paula.bokesch@cubist.com
authors: Paula M
authors: PM
authors: Bokesch
authors: Gabor
authors: G
authors: Szabo
authors: Ryszard
authors: R
authors: Wojdyga
authors: Hilary P
authors: HP
authors: Grocott
authors: Peter K
authors: PK
authors: Smith
authors: C David
authors: CD
authors: Mazer
authors: Santosh
authors: S
authors: Vetticaden
authors: Alistair
authors: A
authors: Wheeler
authors: Jerrold H
authors: JH
authors: Levy
mesh_terms: D000368:Aged; D016063:Blood Loss, Surgical / Q000401:mortality / Q000517:prevention & control*; D006348:Cardiac Surgical Procedures / Q000009:adverse effects* / Q000401:mortality; D002315:Cardiopulmonary Bypass / Q000009:adverse effects* / Q000401:mortality; D004311:Double-Blind Method; D057239:Early Termination of Clinical Trials; D017707:Erythrocyte Transfusion; D005060:Europe; D005260:Female; D006490:Hemostatics / Q000008:administration & dosage* / Q000009:adverse effects; D006801:Humans; D008297:Male; D008875:Middle Aged; D010455:Peptides / Q000008:administration & dosage* / Q000009:adverse effects; D019106:Postoperative Hemorrhage / Q000209:etiology / Q000401:mortality / Q000517:prevention & control*; D011446:Prospective Studies; D018570:Risk Assessment; D012307:Risk Factors; D013997:Time Factors; D014148:Tranexamic Acid / Q000008:administration & dosage* / Q000009:adverse effects; D016896:Treatment Outcome; D014481:United States
chemical_list: D006490:Hemostatics; D010455:Peptides; C511194:ecallantide; D014148:Tranexamic Acid