Low Molecular Weight Heparinoid, ORG 10172 (Danaparoid), and Outcome After Acute Ischemic Stroke: A Randomized Controlled Trial

Abstract

Context.—Anticoagulation with unfractionated heparin is used commonly for treatment of acute ischemic stroke, but its use remains controversial because it has not been shown to be effective or safe. Low molecular 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 stroke.Objective.—To test whether an intravenously administered low molecular weight heparinoid, ORG 10172 (danaparoid sodium), increases the likelihood of a favorable outcome at 3 months after acute ischemic stroke.Design.—Randomized, double-blind, placebo-controlled, multicenter trial.Setting and Participants.—Between December 22, 1990, and December 6, 1997, 1281 persons with acute stroke were enrolled at 36 centers across the United States.Intervention.—A 7-day course of ORG 10172 or placebo was given initially as a bolus within 24 hours of stroke, followed by continuous infusion in addition to the best medical care. Doses were adjusted in response to anti–factor Xa activity.Main Outcome Measures.—Favorable outcome rated as the combination of a Glasgow Outcome Scale score of I or II and a modified Barthel Index of 12 or greater on a scale of 0 to 20 at 3 months or 7 days; very favorable outcome 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 months, 482 (75.2%) of 641 persons assigned to treatment with ORG 10172 and 467 (73.7%) of 634 patients treated with placebo had favorable outcomes (P=.49); 49.5% and 47%, respectively, of patients in each group had very favorable outcomes at 3 months. At 7 days, 376 (59.2%) of 635 persons given ORG 10172 and 344 (54.3%) of 633 receiving placebo had favorable outcomes (P=.07). For the same interval, 215 (33.9%) of 635 persons given ORG 10172 and 176 (27.8%) of 633 persons administered placebo had very favorable outcomes (P=.01; odds ratio, 1.36; 95% confidence 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).Conclusion.—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.