При ОИМ интраартериальный тромболизис не прижился. Посмотрим, как будет в этом случае. Пока, на сей момент, общепризнанной считается методика системного тромболизиза только преператом t-Pa. Считается перспективным применение десмотеплазы, но это еще на стадии изучения.
Dose Escalation of Desmoteplase for Acute Ischemic Stroke (DEDAS)
Evidence of Safety and Efficacy 3 to 9 Hours After Stroke Onset 
Anthony J. Furlan, MD; Dirk Eyding, PhD; Gregory W. Albers, MD; Yasir Al-Rawi, MD; Kennedy R. Lees, MD; Howard A. Rowley, MD; Christian Sachara; Mariola Soehngen, MD; Steven Warach, MD, PhD; Werner Hacke, MD for the DEDAS Investigators
From The Cleveland Clinic (A.F.), Department of Neurology, Cleveland, Ohio; PAION Deutschland GmbH (D.E., Y.A.-R., M.S.), Aachen, Germany; the Stanford Stroke Center (G.A.), Palo Alto, Calif; the Western Infirmery (K.R.L.), University Department of Medicine & Therapeutics, Glasgow, United Kingdom; the University of Wisconsin (H.A.R.), Department of Radiology, Madison, Wis; the ClinResearch GmbH (C.S.), Köln, Germany; the NINDS (S.W.), Bethesda, Md; and the Department of Neurology (W.H.), University of Heidelberg, Heidelberg, Germany.
Correspondence to Anthony J. Furlan, MD, The Cleveland Clinic, Department of Neurology, S91, 9500 Euclid Ave, Cleveland, OH 44195, USA. E-mail [
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Background and Purpose— Desmoteplase is a novel plasminogen activator with favorable features in vitro compared with available agents. This study evaluated safety and efficacy of intravenous (IV) desmoteplase in patients with perfusion/diffusion mismatch on MRI 3 to 9 hours after onset of acute ischemic stroke.
Methods— DEDAS was a placebo-controlled, double-blind, randomized, dose-escalation study investigating doses of 90 µg/kg and 125 µg/kg desmoteplase. Eligibility criteria included baseline National Institute of Health Stroke Scale (NIHSS) scores of 4 to 20 and MRI evidence of perfusion/diffusion mismatch. The safety end point was the rate of symptomatic intracranial hemorrhage. Primary efficacy co-end points were MRI reperfusion 4 to 8 hours after treatment and good clinical outcome at 90 days. The primary analyses were intent-to-treat. Before unblinding, a target population, excluding patients violating specific MRI criteria, was defined.
Results— Thirty-seven patients were randomized and received treatment (intent-to-treat; placebo: n=8; 90 µg/kg: n=14; 125 µg/kg: n=15). No symptomatic intracranial hemorrhage occurred. Reperfusion was achieved in 37.5% (95% CI [8.5; 75.5]) of placebo patients, 18.2% (2.3; 51.8) of patients treated with 90 µg/kg desmoteplase, and 53.3% (26.6; 78.7) of patients treated with 125 µg/kg desmoteplase. Good clinical outcome at 90 days occurred in 25.0% (3.2; 65.1) treated with placebo, 28.6% (8.4; 58.1) treated with 90 µg/kg desmoteplase and 60.0% (32.3; 83.7) treated with 125 µg/kg desmoteplase. In the target population (n=25), the difference compared with placebo increased and was statistically significant for good clinical outcome with 125 µg/kg desmoteplase (P=0.022).
Conclusions— Treatment with IV desmoteplase 3 to 9 hours after ischemic stroke onset appears safe. At a dose of 125 µg/kg desmoteplase appeared to improve clinical outcome, especially in patients fulfilling all MRI criteria. The results of DEDAS generally support the results of its predecessor study, Desmoteplase in Acute Ischemic Stroke (DIAS).
DIAS
Desmoteplase In Acute ischaemic Stroke
Status
Trial complete. Results published in January of 2005. A dose-ranging Phase III trial is being planned.
Purpose
To assess the safety and thrombolytic efficacy of intravenous desmoteplase (vampire bat plasminogen activator) in patients with acute ischemic stroke.
Intervention(s)
Desmoteplase (Thrombolytic agent; reportedly selective for fibrin-bound plasminogen)
Trial Location(s) Austria, Belgium, Finland, France, Germany, Norway, Singapore, Spain, Sweden, Switzerland, UK, Australia
Year Published: 2005
Year Presented: 2004
Study Size Actual: 102
Study Size Planned: 104
Number of Centers 44
Ages Eligible: 18-85
Maximum time from onset: 9 hours
Design
Study Design: Randomized, multi-center, multinational, double-blind, placebo-controlled, dose escalating trial.
Inclusion Criteria: Patients between 18 and 85 years of age, who are between 3 and 9 hours post-ischemic stroke, who score between 4 and 20 on the National Institute of Health Stroke Scale (NIHSS) and show signs of cortical involvement, who receive MRI screening within 8 hours of their strokes that show a perfusion-weighted imaging (PWI) abnormality =< 2 cm in diameter in the hemispheric gray matter, that also either shows no diffusion-weighted imaging (DWI) abnormality, or a PWI/DWI mismatch > 20%, were eligible for the study.
Exclusion Criteria: Females of childbearing potential, persons who weigh < 50 kg (110 lbs), who are ineligible to receive medication within 30 minutes of their MRI, whose strokes are idiopathic, who have a prestroke modified Rankin score (MRS) > 1, who have a history of intracranial hemorrhage (ICH), subarachnoid hemorrhage (SAH), arteriovenous malformation, or aneurysm, whose clinical presentation suggests SAH, who use oral anticoagulants or have an international normalized ratio (INR) > 1.7, who have received heparin within 48 hours or who have a partial thromboplastin time (PTT) > 1.5 times the normal value, who use glycoprotein Iib/IIIa inhibitors, or who have any condition that would confer additional risk while receiving trial medication, will be excluded from the study.
Patient Involvement: Upon admission, prospective participants will undergo a complete history and physical, an MRI, laboratory tests, and other trial-related assessments in order to determine trial eligibility. Desmoteplase will be administered to participants in a single-bolus IV infusion. Patients will undergo 11 assessments during the 3-month trial, in addition to another assessment upon discharge from the hospital.
Primary Outcome: Safety: frequency of symptomatic ICH. Efficacy: reperfusion, assessed by MRA, magnetic resonance angiography; and 90-day clinical outcome, determined by NIHSS, MRS, Barthel Index (BI) scores, and mortality rates.
Results
Part 1: Symptomatic ICH was observed in 4 of the 13 (30.8%) patients in the high-dose group (37.5/50 mg), as well as in 4 of the 17 (23.5%) patients in the low-dose group (25 mg). There were no hemorrhages in the placebo group. Based on this data, trial coordinators continued the study using considerably lower dosage tiers. Part 2: Of the 45 desmoteplase-treated patients, one (2.2%) experienced symptomatic ICH. There were no hemorrhages in the placebo group (n=11). For efficacy, greater improvement in reperfusion was observed in the desmoteplase-treated patients (20 of 42 total; 47.6%), as opposed to patients in the placebo group (2 of 10; 20%). Statistical significance for reperfusion was demonstated in the two higher-dose groups (90 µ/kg and125 µ/kg, p=0.0349 and 0.0012 respectively). 90 day outcome followed a similar dose-dependent trend, with significant improvment observed among the patients (9 of 15) in the high-dose desmoteplase group (p=0.0090).
Source of Information
Correspondence from Paion. Presented at the 29th International Stroke Conference (February 2004). Stroke. Jan 2005;36:66-73.
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