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)

J Thorac Cardiovasc Surg. 2012 May;143(5):1022-9. doi: 10.1016/j.jtcvs.2011.06.001. Epub 2011 Jul 2.

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.

Trial registration: ClinicalTrials.gov NCT00888940.

Publication types

  • Clinical Trial, Phase II
  • Comparative Study
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Blood Loss, Surgical / mortality
  • Blood Loss, Surgical / prevention & control*
  • Cardiac Surgical Procedures / adverse effects*
  • Cardiac Surgical Procedures / mortality
  • Cardiopulmonary Bypass / adverse effects*
  • Cardiopulmonary Bypass / mortality
  • Double-Blind Method
  • Early Termination of Clinical Trials
  • Erythrocyte Transfusion
  • Europe
  • Female
  • Hemostatics / administration & dosage*
  • Hemostatics / adverse effects
  • Humans
  • Male
  • Middle Aged
  • Peptides / administration & dosage*
  • Peptides / adverse effects
  • Postoperative Hemorrhage / etiology
  • Postoperative Hemorrhage / mortality
  • Postoperative Hemorrhage / prevention & control*
  • Prospective Studies
  • Risk Assessment
  • Risk Factors
  • Time Factors
  • Tranexamic Acid / administration & dosage*
  • Tranexamic Acid / adverse effects
  • Treatment Outcome
  • United States

Substances

  • Hemostatics
  • Peptides
  • ecallantide
  • Tranexamic Acid

Associated data

  • ClinicalTrials.gov/NCT00888940