title: Argatroban versus Lepirudin in critically ill patients (ALicia): a randomized controlled trial.
abstract: BACKGROUND
  Critically ill patients often require renal replacement therapy accompanied by thrombocytopenia. Thrombocytopenia during heparin anticoagulation may be due to heparin-induced thrombocytopenia with need for alternative anticoagulation. Therefore, we compared argatroban and lepirudin in critically ill surgical patients.
  
  
  METHODS
  Following institutional review board approval and written informed consent, critically ill surgical patients more than or equal to 18 years with suspected heparin-induced thrombocytopenia, were randomly assigned to receive double-blind argatroban or lepirudin anticoagulation targeting an activated Partial Thromboplastin Time (aPTT) of 1.5 to 2 times baseline. In patients requiring continuous renal replacement therapy we compared the life-time of hemodialysis filters. We evaluated in all patients the incidence of bleeding and thrombembolic events.
  
  
  RESULTS
  We identified 66 patients with suspected heparin-induced thrombocytopenia, including 28 requiring renal replacement therapy. Mean filter lifetimes did not differ between groups (argatroban 32 ± 25 hours (n = 12) versus lepirudin 27 ± 21 hours (n = 16), mean difference 5 hours, 95% CI -13 to 23, P = 0.227). Among all 66 patients, relevant bleeding occurred in four argatroban- versus eleven lepirudin-patients (OR 3.9, 95% CI 1.1 to 14.0, P = 0.040). In the argatroban-group, three thromboembolic events occurred compared to two in the lepirudin group (OR 0.7, 95% CI 0.1 to 4.4, P = 0.639). The incidence of confirmed heparin-induced thrombocytopenia was 23% (n = 15) in our study population.
  
  
  CONCLUSIONS
  This first randomized controlled double-blind trial comparing two direct thrombin inhibitors showed comparable effectiveness for renal replacement therapy, but suggests fewer bleeds in surgical patients with argatroban anticoagulation.
  
  
  BACKGROUND
  Clinical Trials.gov NCT00798525. Registered 25 November 2008.
authors.forename: Tanja A
authors.initials: TA
authors.lastname: Treschan
authors.forename: Maximilian S
authors.initials: MS
authors.lastname: Schaefer
authors.forename: Johann
authors.initials: J
authors.lastname: Geib
authors.forename: Astrid
authors.initials: A
authors.lastname: Bahlmann
authors.forename: Tobias
authors.initials: T
authors.lastname: Brezina
authors.forename: Patrick
authors.initials: P
authors.lastname: Werner
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Golla
authors.forename: Andreas
authors.initials: A
authors.lastname: Greinacher
authors.forename: Benedikt
authors.initials: B
authors.lastname: Pannen
authors.forename: Detlef
authors.initials: D
authors.lastname: Kindgen-Milles
authors.forename: Peter
authors.initials: P
authors.lastname: Kienbaum
authors.forename: Martin
authors.initials: M
authors.lastname: Beiderlinden
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000925:Anticoagulants / Q000009:adverse effects; D000991:Antithrombins / Q000627:therapeutic use*; D001120:Arginine / Q000031:analogs & derivatives; D016638:Critical Illness; D005260:Female; D006470:Hemorrhage / Q000188:drug therapy; D006493:Heparin / Q000009:adverse effects; D006629:Hirudins; D006801:Humans; D008297:Male; D008875:Middle Aged; D010314:Partial Thromboplastin Time; D010875:Pipecolic Acids / Q000627:therapeutic use*; D011994:Recombinant Proteins / Q000627:therapeutic use; D051437:Renal Insufficiency / Q000628:therapy; D017582:Renal Replacement Therapy; D013449:Sulfonamides; D013514:Surgical Procedures, Operative; D013921:Thrombocytopenia / Q000139:chemically induced / Q000628:therapy*
chemical_list: D000925:Anticoagulants; D000991:Antithrombins; D006629:Hirudins; D010875:Pipecolic Acids; D011994:Recombinant Proteins; D013449:Sulfonamides; D006493:Heparin; D001120:Arginine; C031942:argatroban; C083544:lepirudin