Efficacy Study of Recombinant Protein (Ecallantide) to Reduce Blood Loss During Primary Coronary Bypass Grafting or Valve Repair/Replacement

• Cumulative chest tube drainage at 24 hours postoperatively or until chest tube removal [ Time Frame: 24 hours ] [ Designated as safety issue: No ]
• Safety and tolerability of DX-88 (ecallantide) [ Time Frame: 28 days ] [ Designated as safety issue: Yes ]
• Pharmacokinetics of DX-88 (ecallantide) [ Time Frame: 12 hours ] [ Designated as safety issue: No ]

• Cumulative chest tube drainage at 24 hours postoperatively or until chest tube removal
• Safety and tolerability of DX-88 (ecallantide)
• Pharmacokinetics of DX-88 (ecallantide)

The purpose of this study is to evaluate two different dose regimens of ecallantide to determine whether either or both dose regimens reduce blood loss, measured by chest tube drainage, compared to placebo during cardiopulmonary bypass surgery.

This is a placebo-controlled trial. Patients are randomized to intravenous administration of high dose ecallantide, low dose ecallantide, or placebo.

The study is designed to evaluate the potential for transfusion reduction in patients receiving ecallantide undergoing cardiopulmonary bypass during primary coronary bypass graft, isolated valve repair, or isolated valve replacement surgery by measuring thoracic drainage. This study is designed to provide data determining the effect of kallikrein inhibition or kallikrein plus plasmin inhibition, compared to placebo, in reducing chest tube drainage. These data are anticipated to support the dose selection in subsequent larger studies to demonstrate the safety and efficacy of ecallantide. Efficacy, safety and pharmacokinetics of ecallantide will be evaluated in this study.

• Drug: ecallantide
  solution for IV infusion over the duration of the surgical procedure
  Other Name: DX-88
• Drug: placebo
  solution for IV infusion over the duration of the surgical procedure

• Experimental: 1
  DX-88 (ecallantide) - low dose regimen
  Intervention: Drug: ecallantide
• Experimental: 2
  DX-88 (ecallantide) - high dose regimen
  Intervention: Drug: ecallantide
• Placebo Comparator: 3
  Placebo
  Intervention: Drug: placebo

Inclusion Criteria:

• Men and women age 18 to 79
• Elective primary CABG, single valve repair, or single valve replacement requiring CPB and sternotomy
• No plan to use desmopressin acetate (DDAVP), atrial natriuretic hormone, EACA, tranexamic acid or aprotinin during or postoperatively
• Female patients must be non-lactating and not pregnant
• If of childbearing potential, female patients must agree to use adequate contraception for 1 month after receiving study drug

Exclusion Criteria:

• Concomitant surgery
• Planned hypothermic CPB using temperatures less than 28C
• Weight < 55 kg
• Major end organ dysfunction
• Serious intercurrent illness or active infection
• Previous exposure to DX-88 (ecallantide)
• Known allergy to ecallantide or any of its components, fentanyl, midazolam, isoflurane, propofol, morphine, heparin or protamine
• Autologous blood donation ≤ 30 days month prior to surgery
• Known substance abuse
• Receipt of an investigational drug or device within 30 days prior to surgery
• Administration prior to surgery of Eptifibatide, Tirofiban HCl, enoxaparin sodium or other low molecular weight heparin, Clopidogrel, Warfarin, Ticlopidine, Abciximab