Treatment of acute ischemic stroke with the low-molecular-weight heparin certoparin: Results of the TOPAS trial

Background and Purpose-To study the safety and efficacy of the low-molecula r-weight heparin certoparin, we performed a randomized, double-blind, dose- finding multicenter trial in patients with acute ischemic stroke (Therapy o f 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 (Barthe l Index greater than or equal to 90 points) at 3 months. CT was performed a t trial entry, after 7 days, and on clinical deterioration. Results-The proportion of patients with Barthel Index greater than or equal to 90 was not different between treatment arms (61.5%, 60.8%, 63.3%, and 5 6.3% in the 4 groups, respectively; intent-to-treat population). European S troke Scale scores improved in all treatment groups within the first 14 day s to a similar extent. During the follow-up of 6 months, percentages of pat ients 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 oc curred 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 v ein thrombosis but no pulmonary embolism was observed. Conclusions-Dose increase of certoparin up to 8000 U aXa twice daily did no t improve the functional outcome of patients with ischemic stroke. Severe b leeding tended to be more frequent in the highest dose group only.