title: Can recombinant human thrombomodulin increase survival among patients with severe septic-induced disseminated intravascular coagulation: a single-centre, open-label, randomised controlled trial.
abstract: To determine whether treatment with recombinant human thrombomodulin (rhTM) increases survival among patients with severe septic-induced disseminated intravascular coagulation (DIC).
  
  
  
  Single-centre, open-label, randomised controlled trial.
  
  
  
  Single tertiary hospital.
  
  
  
  92 patients with severe septic-induced DIC.
  
  
  
  Patients with DIC scores ≥4, as defined by the Japanese Association of Acute Medicine, were diagnosed with DIC. The envelope method was used for randomisation. The treatment group (rhTM group, n=47) was intravenously treated with rhTM within 24 hours of admission (day 0), and the control group (n=45) did not receive any anticoagulants, except in cases of deep venous thrombosis and pulmonary embolism.
  
  
  
  Data were collected on days 0 (admission), 1, 2, 3, 5, 7 and 10. The primary outcome was survival at 28 and 90 days. The secondary end points comprised changes in DIC scores, platelet counts, d-dimer, antithrombin III and C reactive protein levels, and Sequential Organ Failure Assessment (SOFA) scores. All analyses were conducted on an intent-to-treat basis.
  
  
  
  The 28-day survival rates were 84% and 83% in the control and rhTM groups, respectively (p=0.745, log-rank test). The 90-day survival rates were 73% and 72% in the control and rhTM groups, respectively (p=0.94, log-rank test). Meanwhile, the rates of recovery from DIC (<4) were significantly higher in the rhTM group than in the control group (p=0.001, log-rank test). Relative change from baseline of d-dimer levels was significantly lower in the rhTM group than in the control group, on days 3 and 5.
  
  
  
  rhTM treatment decreased d-dimer levels and facilitated DIC recovery in patients with severe septic-induced DIC. However, the treatment did not improve survival in this cohort.
  
  
  
  UMIN000008339.
authors.affiliation: Department of Emergency Medicine and Critical Care, National Center for Global Health and Medicine, Tokyo, Japan.
authors.forename: Akiyoshi
authors.initials: A
authors.lastname: Hagiwara
authors.affiliation: Biostatistics Section, Department of Data Science Clinical Science Center, National Center for Global Health and Medicine, Tokyo, Japan.
authors.forename: Noriko
authors.initials: N
authors.lastname: Tanaka
authors.affiliation: Department of Emergency Medicine and Critical Care, National Center for Global Health and Medicine, Tokyo, Japan.
authors.forename: Tatsuki
authors.initials: T
authors.lastname: Uemura
authors.affiliation: Department of Emergency Medicine and Critical Care, National Center for Global Health and Medicine, Tokyo, Japan.
authors.forename: Wataru
authors.initials: W
authors.lastname: Matsuda
authors.affiliation: Department of Emergency Medicine and Critical Care, National Center for Global Health and Medicine, Tokyo, Japan.
authors.forename: Akio
authors.initials: A
authors.lastname: Kimura
mesh_terms: D000328:Adult; D000925:Anticoagulants / Q000008:administration & dosage*; D004211:Disseminated Intravascular Coagulation / Q000188:drug therapy* / Q000401:mortality / Q000503:physiopathology; D004305:Dose-Response Relationship, Drug; D005260:Female; D017052:Hospital Mortality; D006801:Humans; D007564:Japan; D008297:Male; D008875:Middle Aged; D063305:Organ Dysfunction Scores; D011446:Prospective Studies; D018805:Sepsis / Q000150:complications* / Q000188:drug therapy / Q000401:mortality / Q000503:physiopathology; D015996:Survival Rate; D018180:Thrombomodulin / Q000008:administration & dosage*; D016896:Treatment Outcome
chemical_list: D000925:Anticoagulants; C546931:THBD protein, human; D018180:Thrombomodulin
keywords: C-reactive protein; D-dimer; disseminated intravascular coagulation; recombinant human thrombomodulin; sepsis; survival