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

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

Official Title
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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

Conditions
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Bloodloss, Surgical Procedures, Operative

Intervention / Treatment
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* Drug: Ecallantide
* Drug: Cyklokapron(R)


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 85 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: ecallantide<br> | Drug: Ecallantide<br>* 2.25 mg/L pump prime, 0.13 mg/kg loading dose, 2.25 mg/L constant infusion<br>|
| Active Comparator: Cyklokapron(R)<br> | Drug: Cyklokapron(R)<br>* 1000-mg loading dose followed by a continuous infusion of 400 mg/hr with an additional 500 mg added to the pump prime<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cumulative Volume of Packed Red Blood Cells Transfused |  | 12 hours after the end of surgery | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Treatment-emergent Adverse Events. |  | Over the duration of the study. |