Study results from University of Perugia broaden understanding of perfusion
2009 AUG 3 - (NewsRx.com) -- "The high fibrin specificity of Desmodus rotundus salivary plasminogen activator alpha 1 (desmoteplase) renders it a promising candidate for the treatment of acute ischemic stroke. In the DIAS (Desmoteplase in Acute Ischemic Stroke) and DEDAS (Dose Escalation study of Desmoteplase in Acute ischemic Stroke) Phase II studies, doses of 90 mu g/kg and 125 mu g/kg desmoteplase were reported to have acceptable safety profiles, leading to potentially superior reperfusion compared with placebo, with possible clinical efficacy for up to 9 h after the onset of symptoms in patients with a significant ischemic penumbra selected from magnetic resonance perfusion-diffusion weighted mismatches imaging," scientists in Perugia, Italy report. "However, a Phase III clinical trial (DIAS-2) was unable to detect any benefit from desmoteplase when given 3 - 9 h after stroke onset. In this study with a modest sample size, certain methodological factors may have reduced its potential to detect a desmoteplase effect, as only 30% of these patients had a visible occlusion at presentation, with only small core and mismatched lesion volumes. indeed, it is surprising that a study testing an occluded vessel 'reopener' was conducted in a cohort of stroke patients, the majority of whom was known not to have a detected vessel occlusion. It has also been claimed that the DIAS-2 patients selection using core/penumbra mismatch calculation may not have followed an appropriate mismatch threshold. However, the corrective value of changing the mismatch threshold remains unclear, because the relative mismatch volumes were in fact higher in the 'negative' DIAS-2 than in the 'positive' DIAS and DEDAS. Two Phase II randomized trials with tPA, Diffusion-weighted imaging Evaluation For Understanding Stroke Evolution (DEFUSE) and Echoplanar Imaging Thrombolytic Evaluation Trial (EPITHET) provided strong biological support for the relation between infarct growth, reperfusion and clinical outcome in the 3 - 6 h time window after onset of stroke using penumbral imaging. In this frame, why exactly desmoteplase should have specific advantages over tPA, is not clear. Taken together, these findings may also lead to the disappointing conclusion that vessel recanalization after 4.5 - 5 h from stroke onset may generally be inefficacious for tissue salvage," wrote M. Paciaroni and colleagues, University of Perugia. The researchers concluded: "Nevertheless, other randomized Phase III clinical trials (DIAS-3 and DIAS-4) are currently under way with a planned sample size of 320 patients having vessel occlusion or high-grade stenosis on MRI or CT-angiography in the proximal cerebral arteries.." Paciaroni and colleagues published their study in Expert Opinion on Biological Therapy (Desmoteplase. Expert Opinion on Biological Therapy, 2009;9(6):773-778). For additional information, contact M. Paciaroni, University of Perugia, Santa Maria Misericordia Hospital, Stroke Unit, I-06126 Perugia, Italy. The publisher's contact information for the journal Expert Opinion on Biological Therapy is: Informa Healthcare, Telephone House, 69-77 Paul Street, London EC2A 4LQ, England. Keywords: Italy, Perugia, Biological Therapy, Biotherapy, Blood Transfusion, Clinical Trial Research, Drug Development, Enzyme Research, Hematology, Magnetic Resonance, Medical Device, Perfusion, Pharmaceuticals, Plasminogen, Reperfusion, Thrombolysis, Transfusion Medicine, Treatment, University of Perugia. This article was prepared by Biotech Business Week editors from staff and other reports. Copyright 2009, Biotech Business Week via NewsRx.com.
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