RANDOMIZED TRIAL OF ORG-10172 IN ACUTE ISCHEMIC STROKE

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Ischemic stoke is the leading neurologic cause of death or disability in the United States. Annually, more than 400,00 Americans have a stroke and the economic costs of this illness exceed $12 billion yearly. No treatment has been demonstrated to be effective in improving outcome after acute ischemic stroke. Regardless of the mechanisms of stroke, an intervention that improves clinical outcome will be valuable. Heparin is the most frequently prescribed drug for treatment of patients with acute ischemic stroke. Despite the sidespread use of heparin, its value in the management of ischemic stroke remains controversial. No trial has determined either the efficacy or lack of usefulness of heparin and no clinical consensus exists. Many physicians are concerned about the safety of heparin because it can be accompanied by potentially life-threatening complications including hemorrhage, thrombocytopenia or arterial thrombosis. Dissociation of the antithrombotic effects of heparin from its anticoagulant and platelet aggregating properties has been achieved in the low molecular weight (LMW) heparinoids. These compounds have a greater margin of safety in regards to bleeding than does heparin and do not affect platelets. Org 10172 is the most extensively studied LMW heparinoid. Our pilot studies have a shown that Org 10172 is relatively safe and well- tolerated in patients with ischemic stroke. We have determined a potentially optimal dosage and treatment regimen. Our results suggest that this treatment may also reduce mortality and morbidity of ischemic stroke. It is a promising therapy but its efficacy for treatment may also reduce mortality and morbidity of ischemic stroke. It is a promising therapy but its efficacy for treatment of acute ischemic stroke has not been proved. Testing the efficacy of Org 10172 will require a randomized clinical trial. We propose a randomized, double-blind, placebo-controlled, clinical trial of Org 10172 in 1300 patients treated within 24 hours of acute ischemic stroke in 20 centers in the United States. Patients will be treated for 7 days and responses will be determined at 7 days and 3 months using the Glasgow Outcome Scale and Barthel Index. The trial is so designed that all safety factors are adequately evaluated. This trial is not testing any putative mechanism of ischemic stroke or reasons for unfavorable outcomes, rather we are testing whether a medical intervention provides any clinical benefit to patients. This trial has been designed to detect an improvement in favorable outcome by 30% with treatment, using intention-to-treat analyses with an alpha of 0.05 and beta of 0.90.