Collagen-thrombin Matrix Efficacy During Cardiac Surgery: a Prospective Randomized Controlled Trial
Condition: Coronary Artery Disease
MeSH terms: Coronary Artery Disease
Study type: Interventional
Phase: Phase 4

Summary: 
      In this prospective open-label randomized trial, 160 patients with elective off-pump coronary
      artery bypass (OPCAB) surgery were enrolled. After primary suture of aortocoronary
      anastomosis, if an area of hemorrhage was identified, patients were randomized to receive
      Floseal® or Collastat® (n=80), respectively. The selected agent was applied with compression
      of the target area for 1 min. If hemostasis was not achieved, the agent was re-applied for a
      further 1 min, and was repeated up to 5 min, after which rescue treatment was applied,
      including any conventional surgical methods.
    

Detailed description: 
      [Patients] A total of 160 patients were enrolled over a 24-month period in a prospective
      randomized controlled trial between March 2018 and Feburary 2020. The Institutional Review
      Board (IRB) at our site approved the study prior to patient enrollment (Severance Hospital,
      South Korea, IRB number; 1-2017-0094), and the study was performed in accordance with the
      ethical standards as laid down in the 1964 Declaration of Helsinki and its later amendments.
      Informed consent was obtained prior to the operative procedure. The inclusion criteria for
      enrollment eligibility specified patients aged 19 years or older, undergoing elective OPCAB
      surgery with multi-vessel coronary artery disease. Patients were excluded if they were
      pregnant or had a known sensitivity to any components of the bovine thrombin preparations or
      the porcine or bovine origin materials. The patients who were taking antithrombotic or
      antiplatelet agents for more than one week, except for aspirin, or who had hematologic
      disease were also excluded from this study.

      [Procedure and scoring system according to hemostatic status] Baseline complete blood count
      with differential, activated partial thromboplastin time (aPTT), prothrombin time,
      electrolyte, and hepatic or renal panel were drawn within 24 hours prior to surgery. Patient
      enrollment occurred in the operating room when an aortocoronary bypass was finally
      determined. After full median sternotomy, heparin (0.7-1.0 mg/kg) was administered to achieve
      the target activated clotting time (ACT; >300 sec). In all patients, a saphenous vein or
      radial artery grafts were anastomosed to the aorta using the Heartstring device (MAQUET
      Holding B.V. & Co. KG, Rastatt, Germany). After identification of an aortocoronary
      anastomosis site, patients were offered the allocated treatment regimen for one of the 2
      hemostatic agents, Floseal® or Collastat®, using the sealed envelope system. The selected
      agent was prepared immediately prior to use after randomization, and was delivered to the
      site of bleeding via a single-barrel syringe, and light compression was applied with a wet
      gauze until the bleeding stopped.

      We defined the scoring system according to hemostasis status including the following details.
      At first, the bleeding site was characterized as oozing or pulsatile. The hemostasis status
      was graded using the 3 steps method (0: no bleeding, 1: oozing, and 2: active bleeding). The
      treatment was applied with pressure to the target area for 1 min. If hemostasis was achieved
      within this time, the time to hemostasis was recorded as 1 min. If hemostasis was not
      achieved, the treatment was re-applied for a further 1 min. if hemostasis was not achieved
      after 5 min, conventional surgical suture was performed.

      Protamine was administered at the end of the OPCAB procedure. The pericardium was loosely
      closed after the surgery, the midline sternotomy was closed in layers, and 2 mediastinal
      drains were left in place. Participants in both groups took aspirin 100 mg and clopidogrel 75
      mg daily from the first postoperative day. Patients with hemoglobin (Hb) values below 60 g/L
      always received transfusion therapy. In stable patients with Hb values between 60 and 100
      g/L, an evaluation of the patients' clinical status was necessary to determine if transfusion
      is warranted (Grade of recommendation: 1C+). Transfusion of fresh frozen plasma (FFP) was
      indicated for the following: correction of congenital deficiencies of clotting factors for
      which a specific concentrate did not exist; for multiple acquired deficiencies; when the
      prothrombin time or aPTT, expressed as a ratio, was greater than 1.5; microvascular bleeding
      in patients undergoing massive transfusion; acute disseminated intravascular coagulation in
      the presence of ongoing bleeding; together with correction of the underlying cause (Grade of
      recommendation: 1C+). The platelet concentrates were indicated if the count was below
      50x109/L and there was ongoing excessive bleeding (Grade of recommendation: 2C).

      [Definition of terms and Endpoint] The following definition was used for application of the
      agents in the clinical setting: successful hemostasis was achieved when there was cessation
      of visible bleeding after completion of the hemostatic agent administration.

      The primary end points were the proportion of patients with complete hemostasis within 5 min
      for the aortocoronary anastomosis site treated by hemostatic agents Floseal® or Collastat®
      and the proportion of patients with complete hemostasis evaluated at 1, 2, and every minute
      up to 5 minutes. Secondary end points were the time required for hemostasis, blood loss in
      the operative day, amount of blood products transfused both intraoperatively and
      postoperatively, rate of surgical revision for bleeding, total length of intensive care unit
      (ICU) stay, and rate of postoperative morbidity/ mortality.
    

Intervention name(s): Collastat; Floseal
Intervention type(s): Drug; Device
Intervention description(s): hemostatic agent that combine porcine-derived collagen thrombin; hemostatic agent that combine bovine-derived gelatin
Other intervention name(s): absorbable collagen hemostasis; absorbable collagen hemostasis
Intervention MeSH terms: Hemostatics
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: In cardiac surgery, patients were randomized to receive Floseal® or Collastat® (n=40), respectively. The selected agent was applied in the operating room.
Masking: Single (Participant)
Primary purpose: Treatment
Keywords: Bleeding; Blood transfusion; Coronary artery bypass surgery; Hemostasis; Topical therapy