Efficacy Study of Recombinant Protein (Ecallantide) to Reduce Blood Loss During Primary Coronary Bypass Grafting or Valve Repair/Replacement
Blood Loss, Surgical
About this trial
This is an interventional prevention trial for Blood Loss, Surgical
Eligibility Criteria
Inclusion Criteria:
- Men and women ≥18 to ≤85 years of age
- Elective primary coronary artery bypass grafting (CABG), single valve repair, or single valve replacement requiring CPB and full sternotomy
- No plan to use desmopressin acetate (DDAVP), atrial natriuretic hormone, E-aminocaproic acid (EACA), tranexamic acid, or aprotinin during or postoperatively
- Female participants must be non-lactating and not pregnant
- If of childbearing potential, female participants must agree to use adequate contraception for 1 month after receiving study drug
Exclusion Criteria:
- Concomitant surgery including but not limited to atrial septal defect repair, multiple valve replacement, carotid endarterectomy, and combined CABG and valve procedure
- Planned hypothermic CPB using temperatures less than 28 degrees Celsius
- Weight <55 kilograms (kg)
Major end organ dysfunction, defined as:
Cardiac:
- Left ventricular ejection fraction (LVEF) < 30% by left ventriculography, echocardiogram, or catheterization (within 90 days prior to screening)
- Use of positive IV inotropic agents within 12 hours prior to surgery
- Preoperative use of intra-aortic balloon pump (IABP), left ventricular assist device (LVAD), or extracorporeal membrane oxygenation (ECMO)
- Renal: Serum creatinine > 1.5 milligrams per deciliter (mg/dL)
- Hepatic: Aspartate aminotransferase (AST) or alanine transferase (ALT) > 2.5 x upper limit normal
Hematologic:
- Preoperative hematocrit (Hct) < 30%
- Platelet count < 100,000/mm^3
- Planned transfusion during surgical procedure
- History or family history of bleeding or clotting disorder (for example, von Willebrand's Disease, idiopathic thrombocytopenia purpura (ITP), thrombotic thrombocytopenia purpura (TTP), hematologic malignancy)
- Prothrombin time (PT) or activated partial thromboplastin time
- (aPTT) > 1.5 x normal range; if receiving unfractionated heparin preoperatively, then abnormal preoperative PT/aPTT permitted
- Serious intercurrent illness or active infection
- Previous exposure to ecallantide
- Known allergy to ecallantide or any of its components, fentanyl, midazolam, isoflurane, propofol, morphine, heparin, or protamine
- Autologous blood donation ≤ 30 days month prior to surgery
- Known substance abuse within 6 months prior to surgery
- Receipt of an investigational drug or device within 30 days prior to participation in the current study
Administration of:
- Eptifibatide < 12 hours prior to surgery
- Tirofiban hydrochloride (HCl) < 12 hours prior to surgery
- Enoxaparin sodium or other low- molecular-weight heparin < 24 hours prior to surgery
- Clopidogrel <5 days prior to surgery
- Warfarin <5 days prior to surgery (Warfarin must be discontinued 5 days prior to surgery and PT must be < 18 seconds)
- Ticlopidine <7 days prior to surgery
- Abciximab <24 hours prior to surgery
Sites / Locations
- St. Vincent's Hospital
- Mayo Clinic Hospital
- University of Colorado
- Massachusetts General Hospital
- Brigham and Women's Hospital
- Caritas St. Elizabeth's Medical Center
- Beth Israel Deaconess Medical Center
- Mayo Clinic
- SUNY Upstate Medical University
- Duke University Medical Center
- Gaston Memorial Hospital
- Cleveland Clinic
- Hospital of the University of Pennsylvania
- The Methodist Hospital
- Texas Heart Institute
Arms of the Study
Arm 1
Arm 2
Arm 3
Experimental
Experimental
Placebo Comparator
Ecallantide - Low Dose Regimen
Ecallantide - High Dose Regimen
Placebo
Participants received a maximum of 15 milligrams (mg) ecallantide in stages. Intravenous (IV) infusion of 0.6 milligrams per milliliter (mg/mL) ecallantide was administered at 2.92 milliliters per minute (mL/min) for 20 minutes. The infusion rate was then reduced to 0.583 mL/min for 160 minutes, or until the end of cardiopulmonary bypass (CPB), whichever came first. At the termination of the initial infusion, a second infusion of 0.4 mg/mL ecallantide was started at 38 milliliters per hour (mL/hr) for 4 hours.
Participants received a maximum of 91 mg ecallantide in stages. IV infusion of 0.6 mg/mL ecallantide was administered at 2.92 mL/min for 20 minutes. The infusion rate was then reduced to 0.583 mL/min for 160 minutes, or until the end of CPB, whichever came first. At the termination of the initial infusion, an infusion of normal saline was started at 38 milliliters per hour (mL/hr) for 4 hours.
Participants received placebo in stages. IV infusion placebo was administered at 2.92 mL/min for 20 minutes. The infusion rate was then reduced to 0.583 mL/min for 160 minutes, or until the end of CPB, whichever came first. At the termination of the initial infusion, a second infusion of placebo was started at 38 mL/hr for 4 hours.