A Dose-ranging Safety and Efficacy Study of Ecallantide to Reduce Surgical Blood Loss Volume

Study Overview
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Brief Summary
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The purpose of this study is to assess the efficacy and identify the optimal dose(s) of ecallantide in reducing blood loss in subjects undergoing coronary artery bypass surgery including the use of cardio pulmonary bypass.

Official Title
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CONSERV-1 (Clinical Outcomes and Safety Trial to Investigate Ecallantide's Effect on Reducing Surgical Blood Loss Volume) A Phase 2 Randomized Placebo-controlled Dose-ranging Study in Subjects Exposed to Cardio-pulmonary Bypass During Primary Coronary Artery Bypass Graft Surgery

Conditions
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Bloodloss, Surgical Procedures, Operative

Intervention / Treatment
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* Drug: ecallantide
* Drug: placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Written informed consent (by study subject or appropriate legal representative) prior to any study-related procedure not part of normal medical care Planned primary CABG surgery including the use of cardio-pulmonary bypass. Exclusion Criteria: Planned concomitant surgery including ASD repair, valve replacement, carotid endarterectomy, CABG combined procedures or any repeat sternotomy; 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, 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 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 or thrombophilia; History of heparin-induced thrombocytopenia; Prothrombin time and/or activated partial thromboplastin time >1.5 X normal range; Serious intercurrent illness or active infection; Any previous exposure to ecallantide; Receipt of an investigational drug or device 30 days prior to participation in the current 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 HCl within 6 hours prior to surgery, *Enoxaparin sodium or other low-molecular-weight heparin <24 hours prior to surgery, Clopidogrel within 5 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, Prasugrel within 10 days prior to surgery [*Prophylactic use permitted for the prevention of deep 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 Low Dose<br>target steady state concentration of 0.15 mg/L | Drug: ecallantide<br>* infusion administered IV over the duration of the surgical procedure<br>|
| Experimental: Ecallantide Medium Dose<br>target steady state concentration of 0.75 mg/L | Drug: ecallantide<br>* infusion administered IV over the duration of the surgical procedure<br>|
| Experimental: Ecallantide High Dose<br>target steady state concentration of 2.25 mg/L | Drug: ecallantide<br>* infusion administered IV over the duration of the surgical procedure<br>|
| Placebo Comparator: Placebo<br>placebo | Drug: placebo<br>* solution for IV infusion over the duration of the surgical>> procedure<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 at 12 Hours Post Surgery |  | Start of surgery up to 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. |