LOW-MOLECULAR-WEIGHT HEPARINOID, ORG-10172 (DANAPAROID), AND OUTCOME AFTER ACUTE ISCHEMIC STROKE - A RANDOMIZED CONTROLLED TRIAL

Context.-Anticoagulation with unfractionated heparin is used commonly for treatment of acute ischemic stroke, but its use remains controvers ial because it has not been shown to be effective or safe. Low molecul ar weight heparins and heparinoids have been shown to be effective in preventing deep vein thrombosis in persons with stroke, and they might be effective in reducing unfavorable outcomes following ischemic stro ke. Objective.-To test whether an intravenously administered low molec ular weight heparinoid, ORG 10172 (danaparoid sodium), increases the l ikelihood of a favorable outcome at 3 months after acute ischemic stro ke. Design.-Randomized, double-blind, placebo-controlled, multicenter trial. Setting and Participants.-Between December 22, 1990, and Decemb er 6, 1997, 1281 persons with acute stroke were enrolled at 36 centers across the United States. Intervention.-A 7-day course of ORG 10172 o r placebo was given initially as a bolus within 24 hours of stroke, fo llowed by continuous infusion in addition to the best medical care. Do ses were adjusted in response to anti-factor Xa activity. Main Outcome Measures.-Favorable outcome rated as the combination of a Glasgow Out come Scale score of I or II and a modified Barthel Index of 12 or grea ter on a scale of 0 to 20 at 3 months or 7 days; very favorable outcom e was recorded for the combination of a Glasgow Outcome Scale of I and a Barthel Index of 19 or 20 at 3 months or 7 days. Results.-At 3 mont hs, 482 (75.2%) of 641 persons assigned to treatment with ORG 10172 an d 467 (73.7%) of 634 patients treated with placebo had favorable outco mes (P=.49); 49.5% and 47%, respectively, of patients in each group ha d very favorable outcomes at 3 months. At 7 days, 376 (59.2%) of 635 p ersons given ORG 10172 and 344 (54.3%) of 633 receiving placebo had fa vorable outcomes (P=.07). For the same interval, 215 (33.9%) of 635 pe rsons given ORG 10172 and 176 (27.8%) of 633 persons administered plac ebo had very favorable outcomes (P=.01; odds ratio, 1.36; 95% confiden ce interval, 1.06-1.73), Within 10 days of onset of treatment, serious intracranial bleeding events occurred in 14 patients given ORG 10172 (15 events) and in 4 placebo-treated patients (5 events) (P=.05). Conc lusion.-Despite an apparent positive response to treatment at 7 days, emergent administration of the antithrombotic agent, ORG 10172, is not associated with an improvement in favorable outcome at 3 months.