Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of MDCO-2010 in Patients Undergoing Elective Coronary Artery Bypass Graft Surgery
Condition: Coronary Artery Bypass Graft; Cardiopulmonary Bypass
Intervention: MDCO-2010; Placebo
Intervention description: MDCO-2010 solution for infusion. Dosage: Pump priming dose; Loading dose infusion over 6 minutes; Maintenance infusion for duration of surgery; Commercially available NaCl
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Single Group Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 32.0
Sex: All
Minimum age: 18 Years
Maximum age: 80 Years
Healthy volunteers: No
Keywords: cardiac surgery; coronary artery bypass graft; cardiopulmonary bypass; haemostasis modulator; blood loss; direct inhibitor of plasmin and plasma kallikrein; CABG; CPB

Summary:

      The purpose of this study is to demonstrate that periprocedural infusion of escalating doses
      of MDCO-2010 is safe and tolerated in patients undergoing elective CABG surgery, to
      characterize the single dose pharmacokinetics of MDCO-2010, to investigate the effect of
      MDCO-2010 on pharmacodynamics (biomarkers of fibrinolysis and coagulation parameters), and to
      investigate the effect on exploratory clinical endpoints of bleeding, transfusion
      requirements and reexploration.
    

Eligibility criteria:

        Inclusion Criteria

          -  Men, aged 18 to 80 years or

          -  Post-menopausal women, aged up to 80 years. Postmenopausal status defined as ≥ 1 year
             since last menstruation in women with no medical history of hysterectomy or women with
             a medical history of bilateral oophorectomy

          -  Planned elective, isolated primary CABG surgery with more than 1 graft, including the
             use of cardiopulmonary bypass

          -  Written informed consent prior to any study-related procedure not part of normal
             medical care

        Exclusion Criteria

        Patients may not meet any of the following exclusion criteria:

          -  Planned concomitant surgery including atrial septal defect (ASD) repair, valve
             replacement, carotid endarterectomy, aortic surgery, any combined procedure or any
             repeat sternotomy

          -  Planned Off-pump CABG

          -  Body weight < 55 kg or > 110 kg

          -  Planned hypothermia < 28°C

          -  Major surgical procedures within 30 days of entry

          -  Placement of drug-eluting stent (DES) within 12 months or of bare-metal stent (BMS)
             within 6 weeks of entry in a vessel which is not intended to be grafted

          -  Ejection fraction < 35%

          -  Preoperative coagulation abnormalities

               -  Platelet count < 100,000/cubic mm, or

               -  INR > 1.5 or Quick < 40%, or

               -  activated partial thromboplastin time (aPTT) > 1.5 x upper limit of normal (ULN)

          -  Preoperative Hb < 11 g/dL for male patients or < 10 g/dL for female patients

          -  Patient refusal to receive donor blood products if necessary

          -  Administration of thienopyridines within 5 days prior to surgery Administration of
             warfarin within 5 days prior to surgery

          -  Administration of tirofiban or eptifibatide within 24 hours or administration of
             abciximab within 5 days prior to surgery

          -  Administration of fondaparinux within 24 hours prior to surgery

          -  Creatinine clearance (calculated using Cockroft-Gault equation) < 60 mL/min

          -  Planned intraoperative use of tranexamic acid or of ε-aminocaproic acid

          -  History of stroke or transient ischemic attack within 3 months prior to entry

          -  Known heparin-induced thrombocytopenia

          -  Known history of thrombophilia, eg, deep vein thrombosis (DVT) with pulmonary embolism

          -  Active liver disease

          -  Any condition requiring chronic immunosuppressive medication

          -  Receipt of an investigational drug or device 30 days prior to entry

          -  Any other condition which, in the opinion of the investigator, would prevent a
             patient's participation in the study