Efficacy Study of Recombinant Protein (Ecallantide) to Reduce Blood Loss During Primary Coronary Bypass Grafting or Valve Repair/Replacement
Condition: Blood Loss, Surgical
MeSH terms: Hemorrhage; Blood Loss, Surgical
Intervention: Ecallantide; Placebo
Intervention MeSH terms: Ecallantide
Phase: Phase 2
Study type: Interventional
Primary purpose: Prevention
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 75.0
Sex: All
Minimum age: 18 Years
Maximum age: 85 Years
Healthy volunteers: No

Summary:

      The primary objective of this study was to assess the efficacy and safety of 2 dose levels of
      ecallantide versus placebo in reducing blood loss following cardiopulmonary bypass (CPB), as
      measured by chest tube drainage during the first 12 hours postoperatively or until the chest
      tube was removed, whichever came first, in patients undergoing primary coronary artery bypass
      grafting (CABG), single valve repair, or single valve replacement.

      The secondary objective was to compare the efficacy of all ecallantide-treated participants
      (pooled high and low-doses) to placebo and to compare the high-dose to the low-dose
      ecallantide group. Other secondary objectives were to evaluate pharmacokinetics and antibody
      formation.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Men and women ≥18 to ≤85 years of age

          -  Elective primary coronary artery bypass grafting (CABG), single valve repair, or
             single valve replacement requiring CPB and full sternotomy

          -  No plan to use desmopressin acetate (DDAVP), atrial natriuretic hormone,
             E-aminocaproic acid (EACA), tranexamic acid, or aprotinin during or postoperatively

          -  Female participants must be non-lactating and not pregnant

          -  If of childbearing potential, female participants must agree to use adequate
             contraception for 1 month after receiving study drug

        Exclusion Criteria:

          -  Concomitant surgery including but not limited to atrial septal defect repair, multiple
             valve replacement, carotid endarterectomy, and combined CABG and valve procedure

          -  Planned hypothermic CPB using temperatures less than 28 degrees Celsius

          -  Weight <55 kilograms (kg)

          -  Major end organ dysfunction, defined as:

               -  Cardiac:

                    -  Left ventricular ejection fraction (LVEF) < 30% by left ventriculography,
                       echocardiogram, or catheterization (within 90 days prior to screening)

                    -  Use of positive IV inotropic agents within 12 hours prior to surgery

                    -  Preoperative use of intra-aortic balloon pump (IABP), left ventricular
                       assist device (LVAD), or extracorporeal membrane oxygenation (ECMO)

               -  Renal: Serum creatinine > 1.5 milligrams per deciliter (mg/dL)

               -  Hepatic: Aspartate aminotransferase (AST) or alanine transferase (ALT) > 2.5 x
                  upper limit normal

               -  Hematologic:

                    -  Preoperative hematocrit (Hct) < 30%

                    -  Platelet count < 100,000/mm^3

                    -  Planned transfusion during surgical procedure

                    -  History or family history of bleeding or clotting disorder (for example, von
                       Willebrand's Disease, idiopathic thrombocytopenia purpura (ITP), thrombotic
                       thrombocytopenia purpura (TTP), hematologic malignancy)

                    -  Prothrombin time (PT) or activated partial thromboplastin time

                    -  (aPTT) > 1.5 x normal range; if receiving unfractionated heparin
                       preoperatively, then abnormal preoperative PT/aPTT permitted

          -  Serious intercurrent illness or active infection

          -  Previous exposure to 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 within 6 months prior to surgery

          -  Receipt of an investigational drug or device within 30 days prior to participation in
             the current study

          -  Administration of:

               -  Eptifibatide < 12 hours prior to surgery

               -  Tirofiban hydrochloride (HCl) < 12 hours prior to surgery

               -  Enoxaparin sodium or other low- molecular-weight heparin < 24 hours prior to
                  surgery

               -  Clopidogrel <5 days prior to surgery

               -  Warfarin <5 days prior to surgery (Warfarin must be discontinued 5 days prior to
                  surgery and PT must be < 18 seconds)

               -  Ticlopidine <7 days prior to surgery

               -  Abciximab <24 hours prior to surgery