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

CONSERV - 2 (Clinical Outcomes and Safety Trial to Investigate Ecallantide's Effect on Reducing Surgical Blood Loss Volume) - A Phase 2 Randomized Double-Blind Active-Controlled Study in Subjects Exposed to Cardio-pulmonary Bypass During Cardiac Surgery at High Risk of Bleeding

A Phase 2 Randomized Double-Blind Active-Controlled Study in Subjects Exposed to Cardio-pulmonary Bypass During Cardiac Surgery at High Risk of Bleeding

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.