Low Molecular Weight Heparinoid, ORG 10172 (Danaparoid), and Outcome After Acute Ischemic Stroke - TOAST
TOAST is a randomized, double-blind, placebo-controlled trial to test whether a low molecular heparinoid (ORG 10172) increases the likelihood of a favorable outcome at 3 months following acute ischemic stroke.
The low molecular heparinoid ORG 10172 may improve outcomes at both 7 days and 3 months following acute ischemic stroke more than placebo.
Patients Screened: 25624
Patients Enrolled: 1281
Mean Follow Up: 3 months
Mean Patient Age: Mean of 65
- 18-85 years old
- Acute or progressing ischemic stroke with symptoms present for more than 1 hour but less than 24 hours
- Prestroke modified Barthel Index of 12 or more
- Resolution of neurologic symptoms
- An isolated mild neurologic deficit
- Stroke less than 24 hours old with recent progression, coma, or mass effect on baseline CT
- Intracranial blood on CT
- CT evidence of nonvascular cause of symptoms
- Active bleeding
- Major surgery within the previous 24 hours
- Abnormal baseline coagulation studies
- Mean blood pressure greater than 130 mm Hg
- Major organ failure
- Known vasculitis or infective endocarditis
- Complex medical illness or terminal illness
- Confounding neurologic disease
- Allergy to heparin
- Prior participation in TOAST
- Women who are pregnant or lactating
Favorable outcome at 3 months, defined as a score of I or II on the Glasgow Outcome Scale and a score of 12-20 on the modified Barthel Index.
- Favorable outcome at 7 days
- Reducing recurrent stroke within 7 days
- Halting worsening of neurologic deficits within 7 days
- Reducing mortality at 7 days and 3 months
- 7-day course of ORG 10172 titrated to maintain an anti-factor Xa level of 0.6-0.8.
Concomitant use of aspirin, heparin, warfarin, ticlopidine and NSAIDs was prohibited during this period
- At 3 months, 482 (75.2%) of patients randomized to ORG 10172 vs. 467 (73.7%) of those in the placebo group had a favorable neurologic outcome, p=0.49
- At 7 days 376 (59.2%) of those in the ORG 10172 vs. 344 (54.3%) of those in the placebo group had favorable neurologic outcomes, p=0.07
- 215 (33.9%) in the ORG 10172 vs. 176 (27.8%) of the placebo group had very favorable neurologic outcome at 7 days, p=0.01
- Serious intracranial bleeding events occurred in 14 patients given ORG 10172 vs. 4 patients in placebo group, p=0.05)
Among patients with acute ischemic stroke, treatment with ORG 10172 (Danaparoid) demonstrated no significant difference in favorable neurologic outcomes at 3 months compared with placebo. Patients randomized to the ORG 10172 group had a significantly higher rate of very favorable outcomes at 7 days. There was, however, a significant association of ORG 10172 administration and serious intracranial bleeding within 10 days.
The Publications Committee for the Trial of ORG 10172 in Acute Stroke Treatment (TOAST). Low Molecular Weight Heparinoid, ORG 10172 (Danaparoid), and Outcome After Acute Ischemic Stroke. JAMA,1998; 279:1265-1272.
Keywords: Dermatan Sulfate, Heparinoids, Stroke, Chondroitin Sulfates, Heparin, Heparitin Sulfate, Factor Xa
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