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.
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.
Diener
H C
HC
Neurologische Klinik und Poliklinik, Universit¿tsklinikum Essen, Hufelandstra¿e 55, 45122 Essen, Germany. h.diener@uni-essen.de
Ringelstein
E B
EB
von Kummer
R
R
Langohr
H D
HD
Bewermeyer
H
H
Landgraf
H
H
Hennerici
M
M
Welzel
D
D
Gräve
M
M
Brom
J
J
Weidinger
G
G
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
D000925:Anticoagulants; D065427:Factor Xa Inhibitors; D006495:Heparin, Low-Molecular-Weight; C403769:certoparin