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
Condition: Bloodloss; Surgical Procedures, Operative
MeSH terms: Blood Loss, Surgical
Intervention: Ecallantide; Cyklokapron(R)
Intervention description: 2.25 mg/L pump prime, 0.13 mg/kg loading dose, 2.25 mg/L constant infusion; 1000-mg loading dose followed by a continuous infusion of 400 mg/hr with an additional 500 mg added to the pump prime
Intervention MeSH terms: Ecallantide; Tranexamic Acid
Phase: Phase 2
Study type: Interventional
Primary purpose: Prevention
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 243.0
Sex: All
Minimum age: 18 Years
Maximum age: 85 Years
Healthy volunteers: No

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.