Albumin in Cardiac Surgery
Condition: C.Surgical Procedure; Cardiac
Study type: Interventional
Phase: Phase 4

Summary: 
      Colloid solutions are widely used for volume replacement therapy because of their high
      oncotic pressure, which could reduce interstitial fluid shifting. Human albumin is the only
      colloid solution of biologic origin with a molecular weight of 60 kDa. As the most abundant
      plasma protein, it has physiological importance in the well-being of the endothelial
      glycocalyx. Older studies in septic patients, however, did not show any benefit of albumin
      over saline solution. Crystalloid solutions, such as Ringer's acetate, do not impair neither
      renal function nor coagulation, but their volume expanding effect is questionable.

      For several reasons (use of heart-lung machine, systemic inflammation, coagulation
      disturbances), patients undergoing cardiac surgery need especially large amounts of fluids.
      However, there are no large trials comparing albumin solutions to crystalloid solutions
      cardiac surgery.

      This double-blinded trial will randomize according to a power analysis 1250 cardiac surgery
      patients (=625+625) at Meilahti hospital to use either 4% Albumin or Ringer's acetate
      solutions for both priming of the heart-lung machine and perioperative volume replacement
      therapy. The primary efficacy and safety endpoint of this study is the incidence of major
      adverse events (MAE), defined as a composite endpoint of all-cause mortality, acute
      myocardial infarction, acute heart failure or low output syndrome, resternotomy, stroke,
      certain arrhythmias, major bleeding, infections compromising post-procedural rehabilitation,
      acute kidney injury within 90 days postoperatively. The secondary outcomes are total number
      of MAEs, major adverse cardiac events (MACE), perioperative fluid balance, blood product
      transfusions, blood loss, acute kidney injury, days alive without mechanical
      ventilation/outside ICU/at home in 90 days as well as 90-day mortality. Blood samples for
      biochemical analyses will be collected at four perioperative time points.

      This trial will provide data about efficacy and safety of 4% albumin in cardiac surgery
      patients. The biochemical mechanisms of albumin will be assessed.
    

Detailed description: 
      The use of cardiopulmonary bypass (CPB) between two study solutions: albumin solution with
      the final concentration of 4% and Ringer's acetate solution. The trial consists of two phases
      as follows. For each patient, one and the same study solution will used in both phases of the
      trial according to randomization.

      In the first phase of the trial, the study solution will be used for priming of the CPB
      tubing. The CPB priming volume comprises only of the study solution. See the Blinding section
      below for more details.

        -  Albumin group (trial group): A mixture of 20% (200 mg/mL) albumin solution (Albuman® 200
           g/L, Sanquin, the Netherlands) with Ringer's acetate solution (see below) in the final
           albumin concentration of 4%.

        -  Ringer group (conventional group): Ringer's acetate solution (Ringer-acetate®, Baxter;
           pH 6.0, contents Na+ 131 mmol/L, Cl- 112 mmol/L, acetate 30 mmol/L) alone.

      In the second phase of the trial, during surgery and the first 24 hours of ICU treatment,
      study solution will be used up to 3200 mL for volume replacement therapy. Ringer's acetate
      solution is used thereafter, i.e. if more than 3200 mL are needed for volume replacement
      therapy during the second study phase. The volume replacement therapy is not protocolled but
      will be based on the clinical decision.

      Albumin group (trial group):4% (40 mg/mL) albumin(Albuman®, Sanquin, the Netherlands)

      •Ringer group (conventional group): Ringer's acetate solution (Ringer-acetate®, Baxter; pH
      6.0, contents Na+ 131 mmol/L, Cl- 112 mmol/L, acetate 30 mmol/L) The trial will end after the
      first 24 hours of ICU treatment or when the patient leaves the ICU if the latter occurs
      within the first postoperative 24 hours. After the study period, fluids are administered
      according to the local clinical practice.

      The use of blood products, excluding albumin, is not protocolled, but will be based on the
      clinical decision.

      For physiological basic need of fluid, Ringer's acetate solution will be given throughout the
      study period, i.e. during surgery and postoperatively, as a background infusion of 0.5
      ml/kg/h, rounded to the nearest multible of 10 ml.
    

Intervention name(s): Albumin solution; Ringers acetate solution
Intervention type(s): Drug; Drug
Intervention description(s): Albumin solution will used for priming of the CPB(cardio-pulmonary bypass) tubing. : A mixture of 20% (200 mg/mL) albumin (Albuman® 200 g/L, Sanquin, the Netherlands) with Ringer's acetate solution in the final albumin concentration of 4%.
During surgery and the first 24 hours of ICU treatment, albumin 4% solution will be used up to 3200 mL for volume replacement therapy. Ringer's acetate solution is used thereafter, i.e. if more than 3200 mL are needed for volume replacement therapy.The volume replacement therapy is not determined but will be based on the clinical decision.; The Ringers acetate solution will be used for priming of the CPB tubing. The CPB priming volume comprises only of Ringer´s solution.
During surgery and the first 24 hours of ICU treatment,Ringer´s acetate solution will be used up to 3200 mL for volume replacement therapy. Ringer's acetate solution is used thereafter, i.e. if more than 3200 mL are needed for volume replacement therapy during the second study phase. The volume replacement therapy is not determined but will be based on the clinical decision.
Other intervention name(s): Albumin
Intervention MeSH terms: Pharmaceutical Solutions
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Treatment
Keywords: human serum albumin solution; Cardiopulmonary Bypass