RiaSTAP vs. Conventional Transfusion in Patients Having Heart Valve Surgery
Condition: Heart Valve Disease; Coronary Artery Disease
MeSH terms: Coronary Artery Disease; Heart Valve Diseases
Intervention: Human fibrinogen concentrate; apheresis platelets
Intervention description: 4 g IV once, within 30 minutes of ACT < 155 seconds, post CPB, with evidence of significant microvascular bleeding; A single apheresis platelet unit will be administered as an initial therapy within 30 minutes of ACT <155 seconds post CPB with evidence of significant microvascular bleeding.
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 26.0
Sex: All
Minimum age: 18 Years
Maximum age: 85 Years
Healthy volunteers: No
Keywords: Hemostasis; Cardiopulmonary bypass (heart-lung machine); Fibrinogen; platelet

Summary:

      Heart surgery involving valve replacement often involves the use of the heart-lung machine
      for over 90 minutes, and bleeding tendency is frequently seen. Conventionally, platelet
      transfusion has been the primary therapy to treat bleeding after this type of procedure. More
      recently, perioperative supplementation of purified fibrinogen (RiaSTAP, CSL Behring) was
      shown to reduce bleeding and blood product use (plasma or platelets) after heart surgery. The
      objective of this trial is to demonstrate the clinical equivalency and economic utility of
      using fibrinogen concentrate, RiaSTAP for the mitigation of post-operative bleeding in
      patients in lieu of platelet transfusion.

      Purified fibrinogen concentrate has been approved by FDA, and it has been used for the
      treatment of acute bleeding episodes in patients with low fibrinogen due to hereditary causes
      (e.g., afibrinogenemia). Compared to the transfusion of platelets which may be associated
      with volume overload, bacterial/viral infection, immunological effects and excess blood
      clotting, purified fibrinogen has several advantages. First, it contains no liquid plasma
      allowing for low volume infusion. Several viral inactivation/reduction steps are used to
      prepare the fibrinogen concentrate, increasing its viral safety. No antibodies or white blood
      cells are contained in the fibrinogen concentrate; therefore transfusion reactions are rare.
      Although platelet transfusion is widely used after heart surgery, there has been no
      randomized study to endorse this practice. In this study, patients undergoing heart valve
      replacement will be randomized to receive either platelet (1 unit) transfusion or fibrinogen
      concentrate (4g) after heparin anticoagulation is reversed. Subjects will be treated only if
      there is evidence of significant microvascular bleeding. Fifteen minutes after the initial
      treatment, subjects will be reevaluated for bleeding. If bleeding continues, subjects will be
      treated with blood transfusion per institutional standard of care.

      The primary endpoints for this study are the hemostatic condition of the surgical field and
      24-hour total of blood product transfusion.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Willing and able to provide written informed consent

          -  Age >17 and < 86 years

          -  Patients undergoing planned cardiopulmonary bypass (CPB) for:

               1. combined coronary artery bypass grafting and valve replacement/repair surgery

               2. single valve replacement surgery

               3. mitral valve repair surgery

             3. or double valve surgery (aortic and mitral)

          -  Presence of clinically relevant microvascular bleeding after protamine administration
             (hemostasis assessment score of 2-3)

          -  Patients should fulfill the following parameters prior to the study intervention:

               -  Body temperature > 35.0°C

               -  Blood pH > 7.2

               -  Hb > 7.0 mg/dL

               -  Activated clotting time (ACT) < 155 seconds

               -  CPB time > 60 minutes

        Exclusion Criteria:

          -  Replacement of aorta

          -  Planned valve replacement without median sternotomy

          -  Previous valve replacement surgery (previous coronary artery bypass graft (CABG)
             acceptable)

          -  History or suspicion of a congenital or acquired coagulation disorder such as
             hemophilia, von Willebrand disease, and liver disease

          -  Hemodialysis dependent renal failure

          -  Liver dysfunction (aspartate aminotransferase (AST) or alanine aminotransferase (ALT)
             increased ≥ 2-fold above the upper limit of local laboratory normal ranges)

          -  Known allergy/anaphylaxis to fibrinogen concentrate or apheresis platelet units

          -  Clopidogrel administration within 5 days of surgery

          -  Coumadin (warfarin) administration within 5 days of surgery

          -  Participation in another clinical study in the 4 weeks preceding surgery

          -  Any indication that a potential subject did not comprehend the study restrictions,
             procedures, or consequences therein an informed consent cannot be convincingly given

          -  Life expectancy less than 48 hours