outcomes and safety trial investigating ecallantide's effect on reducing surgical blood loss volume in subjects at high risk of bleeding exposed to cardio-pulmonary bypass during cardiac surgery

Conditions: Bloodloss; Surgical Procedures, Operative

Summary: a phase 2 randomized double-blind active-controlled study in subjects exposed to cardio-pulmonary bypass during cardiac surgery at high risk of bleeding


Eligibility criteria:
inclusion criteria: * written informed consent (by study subject) prior to any study-related procedure not part of normal medical care; * male or female between the ages of 18 and 85 years old, inclusive; and * planned cardiac surgery using cardio-pulmonary bypass, for one of the following procedures: any repeat sternotomy; surgery to repair or replace more than one valve; combined cabg plus repair or replacement of at least one valve * if female, subject is non-lactating, and is either:not of childbearing potential, defined as postmenopausal for at least one year or surgically sterile due to bilateral tubal ligation, bilateral oophorectomy, or hysterectomy;of childbearing potential but is not pregnant as confirmed by negative pregnancy test at time of screening (based on the β-subunit of hcg), and is practicing the barrier method of birth control along with one of the following methods: oral or parenteral contraceptives for three months prior to study drug administration, a vasectomized partner, or abstinence from sexual intercourse. exclusion criteria: * planned primary cabg, single valve repair or replacement surgery, or any off pump procedure; * body weight \<55 kg; * planned hypothermia (\<28ºc); * planned transfusion in the peri-operative or post-operative periods; * planned transfusion of pre-operatively donated autologous blood; * female subjects who are pregnant or lactating; * planned use of desmopressin, lysine analogs (other than study medication), atrial natriuretic hormone or recombinant activated factor vii; * planned use of corticosteroids in the pump prime solution; * ejection fraction \<30% within 90 days prior to surgery; * evidence of a myocardial infarction within 5 days prior to surgery; * history of stroke or transient ischemic attack within 3 months prior to surgery; * hypotension or heart failure requiring the use of inotropes or mechanical devices within 24 hours prior to surgery; * serum creatinine \>2.0 mg/dl within 48 hours prior to surgery; * serum hepatic enzymes (aspartate aminotransferase or alanine aminotransferase) above 2.5 times the upper limit of normal for the applicable laboratory; * hematocrit \<32% within 48 hours prior to surgery; * platelet count below the normal range for the applicable laboratory within 14 days prior to surgery; * history of, or family history of, bleeding or clotting disorder (e.g. von willebrand's disease, idiopathic thrombocytopenia purpura) or thrombophilia such as anti-thrombin iii deficiency or factor v leiden mutation; * history of heparin-induced thrombocytopenia; * prothrombin time (pt) and/or activated partial thromboplastin time (aptt) \>1.5 x normal range unless subject received heparin within 24 hours of test; * serious intercurrent illness or active infection (e.g. endocarditis, sepsis, active malignancy requiring treatment); * any previous exposure to ecallantide; * receipt of an investigational drug or device 30 days prior to participation in the current study; * any other condition that, in the opinion of the investigator, may compromise the safety or compliance of the subject or would preclude the subject from successful completion of the study; * inability to comply with the protocol for the duration of the study; * known allergy to any agent expected to be used in the intra-operative or post-operative periods; and * administration of: eptifibatide within 6 hours prior to surgery, tirofiban hydrochloride within 6 hours prior to surgery, (enoxaparin sodium or other low-molecular-weight heparin \<24 hours prior to surgery), prasugrel within 10 days prior to surgery, clopidogrel within 3 days prior to surgery, ticlopidine within 7 days prior to surgery, abciximab within 5 days prior to surgery, (bivalirudin, argatroban or lepirudin within 6 hours prior to surgery), (fondaparinux within 72 hours prior to surgery), chlorpromazine within 7 days prior to surgery (prophylactic use permitted for the prevention of deep vein thrombosis.) * planned use of heparin bonded bypass circuits; * known allergy or hypersensitivity to tranexamic acid or any of the other ingredients; * disturbance of color sense; * evidence of hematuria or any acute thromboses or thromboembolic diseases such as deep vein thrombosis, pulmonary embolism, or vertebral vein thrombosis.