类别
»
Primary study
報告»Medscape Medical News
Year
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2007
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Preliminary results of the Desmoteplase In Acute Ischemic Stroke 2 (DIAS-2) trial show no benefit of either of 2 doses of desmoteplase, a novel thrombolytic agent derived from vampire-bat saliva, over placebo. Mortality was actually increased with the 125-µg/kg dose vs both placebo and the 90-µg/kg dose, although the excess deaths occurred late after treatment and were predominantly nonneurological, and there was no excess in intracerebral hemorrhage (ICH) between groups. Werner Hacke, MD, from the University of Heidelberg, in Germany, cochair of the steering committee for the DIAS-2 trial, presented the disappointing findings at the 16th European Stroke Conference, in Glasgow, Scotland. "It simply does not make real sense, what we are seeing here," Dr. Hacke said. DIAS-2 DIAS-2 was a prospective, double-blind, single-bolus study investigating the efficacy and safety of 2 doses of desmoteplase, 90 and 125 µg/kg, given as an intravenous bolus. Two phase 2 trials of desmoteplase, DIAS and DEDAS, had been previously reported and provided encouraging data on both the safety and potential efficacy out to 9 hours after stroke onset with this agent. Patients were eligible for DIAS-2 if they could be treated within 3 and 9 hours after the onset of stroke symptoms, had a score on the National Institutes of Health Stroke Scale (NIHSS) of 4 to 20, and had a distinct ischemic penumbra of at least 20% established by magnetic resonance imaging (MRI) (perfusion-weighted imaging /diffusion-weighted imaging ) or perfusion computed tomography (CT). The primary outcome was clinical improvement at day 90, defined as having achieved all of the following: an improvement in NIHSS score of 8 points or more (or an NIHSS score of < 1), Barthel Index score of 75 to 100, and a modified Rankin Scale score of 0 to 2. On October 25, 2006, Paion AG, in Aachen, Germany, announced that the trial had been halted by the data monitoring committee (DMC) for apparent safety concerns, the precise nature of which the DMC did not disclose. However, on October 30, the trial was allowed to resume enrollment without modification of the protocol, and the data remained blinded. Now it is clear what had given the DMC pause. Using intention-to-treat analysis, investigators found no significant difference between the groups in clinical response rates, with numbers that contrasted sharply with their previous findings with this agent. "This is far from our expectations," Dr. Hacke said. "This pattern makes no sense, specifically when we look at what we had seen in the previous randomized trials — everything is turned upside down." When they considered clinical response rates without dropouts, he noted, "The picture changes slightly; now we have an equal response in all treatment arms, but not what we had expected."
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First added on: Oct 28, 2015