Showing papers by "Werner Hacke published in 2005"

The Desmoteplase in Acute Ischemic Stroke Trial (DIAS): A Phase II MRI-Based 9-Hour Window Acute Stroke Thrombolysis Trial With Intravenous Desmoteplase

Abstract: Background and Purpose— Most acute ischemic stroke patients arrive after the 3-hour time window for recombinant tissue plasminogen activator (rtPA) administration. The Desmoteplase In Acute Ischemic Stroke trial (DIAS) was a dose-finding randomized trial designed to evaluate the safety and efficacy of intravenous desmoteplase, a highly fibrin-specific and nonneurotoxic thrombolytic agent, administered within 3 to 9 hours of ischemic stroke onset in patients with perfusion/diffusion mismatch on MRI. Methods— DIAS was a placebo-controlled, double-blind, randomized, dose-finding phase II trial. Patients with National Institute of Health Stroke Scale (NIHSS) scores of 4 to 20 and MRI evidence of perfusion/diffusion mismatch were eligible. Of 104 patients, the first 47 (referred to as Part 1) were randomized to fixed doses of desmoteplase (25 mg, 37.5 mg, or 50 mg) or placebo. Because of an excessive rate of symptomatic intracranial hemorrhage (sICH), lower weight-adjusted doses escalating through 62.5 μg/kg, ...

Critical Care and Emergency Medicine Neurology in Stroke

Abstract: Dramatic changes have occurred in the area of critical care and emergency stroke treatments of intracerebral hemorrhage (ICH). New data from three sponsored clinical trials: STICH (British National Health System-Medical Research Council), NOVO Seven (Novonordisk), and intraventricular hemorrhage (IVH) clot lysis (FDA Orphan Drug Program)1 were presented at the 29th International Stroke Meeting2 and the World Stroke Congress. Several avenues of approach to the problem of ICH are opening. Although the data from these trials are now under peer review, the initial presentations have demonstrated several principles that seem clear. First, craniotomy (though not better than initial medical management) is safe and not worse than initial medical management. Second, deterioration occurs frequently (≈25% of the time) in the initial days after ICH. Deterioration was treated with surgery. Third, a strategy of emergent clot stabilization is safe and shows trends toward efficacy in the NOVO Seven dose finding study.2 Finally, catheter-assisted removal of blood clot from the obstructed ventricular system in IVH can be accomplished safely with low dose recombinant tissue plasminogen activator (rtPA).3 These trial results suggest that the basic elements of aneurysm care are now being applied to ICH care: emergent stabilization of the bleeding site, followed by removal of blood and management of cranial vault mechanics. Data are now beginning to support that applying these principles leads to improvement in mortality and morbidity. We hope that the robustness of the peer-reviewed data continues to point to the value of emergent intervention for the ICH patient. New sponsored trials have already started: CLEAR IVH, a phase IIb dose optimization trial directed at finding the best dose of rtPA to rapidly remove blood from the ventricles (FDA Orphan drug program)4; MISTIE, an NIH sponsored phase II safety study of minimally invasive surgery plus …

Akute zerebrale Durchblutungsstörung

Abstract: Acute stroke is the third most common cause of death and also the most common cause of permanent disability in industrialized countries. Ischemic stroke is caused by occlusion of a cerebral artery leading to a critical reduction in brain perfusion in the respective brain area (penumbra). Most acute stroke treatment strategies are based on the penumbra concept: attaining rapid and persistent reperfusion is followed by the protection of critically ischemic and not yet infarcted (penumbral) tissue by, e.g., neuroprotection. Examination of the acute stroke patient includes a brief history, neurostatus and imaging (CT or MRI) for the exclusion of intracerebral hemorrhage. The diagnostic standard is CT; modern stroke MRI protocols provide an improved selection in later time windows. Intravenous thrombolysis with rt-PA within 3 h of symptom onset is the only approved therapy with a proven significant benefit for the patient. The effect is smaller but still significant if treatment occurs up to 4.5 h, and may still be present in MRI selected patients up to 9 h. More aggressive forms of therapy include interventional reperfusion techniques and therapy of malignant MCA infarction such as hemicraniectomy and hypothermia, which at present, however, are not routine and are only performed in specialized centers.