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

BACKGROUND AND PURPOSE:

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: H C Diener, E B Ringelstein, R von Kummer, H D Langohr, H Bewermeyer, H Landgraf, M Hennerici, D Welzel, M Gräve, J Brom, G Weidinger
• Journal: Stroke (Stroke) Vol. 32 Issue 1 Pg. 22-9 (Jan 2001) ISSN: 1524-4628 [Electronic] United States
• PMID: 11136909 (Publication Type: Clinical Trial, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Anticoagulants
• Factor Xa Inhibitors
• Heparin, Low-Molecular-Weight
• certoparin

Topics

• Adolescent
• Adult
• Aged
• Aged, 80 and over
• Anticoagulants (administration & dosage, adverse effects)
• Brain Ischemia (complications, diagnostic imaging, drug therapy)
• Dose-Response Relationship, Drug
• Double-Blind Method
• Drug Administration Schedule
• Factor Xa Inhibitors
• Female
• Follow-Up Studies
• Germany
• Hemorrhage (etiology)
• Heparin, Low-Molecular-Weight (administration & dosage, adverse effects)
• Humans
• Male
• Middle Aged
• Recurrence
• Severity of Illness Index
• Stroke (complications, diagnostic imaging, drug therapy)
• Survival Rate
• Tomography, X-Ray Computed
• Treatment Outcome