title: Treatment of acute ischemic stroke with the low-molecular-weight heparin certoparin: results of the TOPAS trial. Therapy of Patients With Acute Stroke (TOPAS) Investigators.
abstract: OBJECTIVE
  To study the safety and efficacy of the low-molecular-weight heparin certoparin, we performed a randomized, double-blind, dose-finding multicenter trial in patients with acute ischemic stroke (Therapy of Patients With Acute Stroke [TOPAS]).
  
  
  METHODS
  We randomized 404 patients to 4 treatment groups within 12 hours of stroke onset: 3000 U anti-factor Xa (aXa) certoparin once daily (treatment group 1); 3000 U aXa twice daily (group 2); 5000 U aXa twice daily (group 3); and 8000 U aXa twice daily (group 4). The primary efficacy variable was the proportion of patients reaching a favorable functional outcome (Barthel Index >/=90 points) at 3 months. CT was performed at trial entry, after 7 days, and on clinical deterioration.
  
  
  RESULTS
  The proportion of patients with Barthel Index >/=90 was not different between treatment arms (61.5%, 60.8%, 63.3%, and 56.3% in the 4 groups, respectively; intent-to-treat population). European Stroke Scale scores improved in all treatment groups within the first 14 days to a similar extent. During the follow-up of 6 months, percentages of patients with recurrent stroke/transient ischemic attack were 11.0%, 5.9%, 9.7%, and 13.0% in the 4 groups, respectively. Overall mortality was only 7.4%. Two parenchymal cerebral hematomas and 1 extracranial bleeding episode occurred in treatment group 1 versus 1 and 0 in group 2, 2 and 0 in group 3, and 4 and 5 in group 4, respectively. During certoparin treatment, 1 deep vein thrombosis but no pulmonary embolism was observed.
  
  
  CONCLUSIONS
  Dose increase of certoparin up to 8000 U aXa twice daily did not improve the functional outcome of patients with ischemic stroke. Severe bleeding tended to be more frequent in the highest dose group only.
authors.affiliation: Neurologische Klinik und Poliklinik, Universit¿tsklinikum Essen, Hufelandstra¿e 55, 45122 Essen, Germany. h.diener@uni-essen.de
authors.forename: H C
authors.initials: HC
authors.lastname: Diener
authors.forename: E B
authors.initials: EB
authors.lastname: Ringelstein
authors.forename: R
authors.initials: R
authors.lastname: von Kummer
authors.forename: H D
authors.initials: HD
authors.lastname: Langohr
authors.forename: H
authors.initials: H
authors.lastname: Bewermeyer
authors.forename: H
authors.initials: H
authors.lastname: Landgraf
authors.forename: M
authors.initials: M
authors.lastname: Hennerici
authors.forename: D
authors.initials: D
authors.lastname: Welzel
authors.forename: M
authors.initials: M
authors.lastname: Gräve
authors.forename: J
authors.initials: J
authors.lastname: Brom
authors.forename: G
authors.initials: G
authors.lastname: Weidinger
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000925:Anticoagulants / Q000008:administration & dosage* / Q000009:adverse effects; D002545:Brain Ischemia / Q000150:complications / Q000000981:diagnostic imaging / Q000188:drug therapy*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D065427:Factor Xa Inhibitors; D005260:Female; D005500:Follow-Up Studies; D005858:Germany; D006470:Hemorrhage / Q000209:etiology; D006495:Heparin, Low-Molecular-Weight / Q000008:administration & dosage* / Q000009:adverse effects; D006801:Humans; D008297:Male; D008875:Middle Aged; D012008:Recurrence; D012720:Severity of Illness Index; D020521:Stroke / Q000150:complications / Q000000981:diagnostic imaging / Q000188:drug therapy*; D015996:Survival Rate; D014057:Tomography, X-Ray Computed; D016896:Treatment Outcome
chemical_list: D000925:Anticoagulants; D065427:Factor Xa Inhibitors; D006495:Heparin, Low-Molecular-Weight; C403769:certoparin