Dr. Anthony Furlan of the Cleveland Clinic Foundation in Ohio said that the reperfusion rate in patients randomized to 125 micrograms/kilogram IV desmoteplase was 53.3%, compared with 37.5% in the placebo arm.

Dr. Furlan presented results of the Dose Escalation study of Desmoteplase in Acute Ischemic Stroke (DEDAS) at a late-breaking clinical trials session Friday at the American Stroke Association International Stroke Conference 2005.

A second desmoteplase dose -- 90 micrograms/kilogram -- was not superior to placebo (18.2% reperfusion rate). However this dose was effective in an earlier European study and Dr. Furlan said it will be investigated in a large, multinational study of desmoteplase that will begin enrollment in April.

"In terms of safety, there were no symptomatic intracerebral hemorrhages," he said. An earlier study of desmoteplase reported one symptomatic intracerebral hemorrhage. "Combining both studies the hemorrhage rate was 2%, which is less than the 6% hemorrhage rate reported with tPA," he said.

The study randomized 38 acute ischemic stroke patients within 3 to 9 hours of stroke onset. Dr. Furlan presented results of the intention-to-treat analysis of 37 patients. Entry criteria included a National Institutes of Health Stroke Score (NIHSS) of 4 to 20. Moreover, Dr. Furlan said this is the first clinical trial to use MRI perfusion/diffusion mismatch as an eligibility criteria -- patients were required to have at least a 20% PWI/DWI mismatch on MRI.

Eight patients were randomized to placebo, 14 to 90 microgram/kilogram or 15 to 125 micrograms/kilogram of desmoteplase. At 90 days, 9 patients in the high-dose arm had clinical improvement (60%) versus 2 in the placebo arm (25%) and 4 in the lower dose arm (28.6%), but Dr. Furlan said these results were not clinically significant "because the study was too small to demonstrate significance."

The study was funded by Paion Pharmaceutical in Aachen, Germany. The phase III trial will be supported by Forest Pharmaceuticals of St. Louis.

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