The new england journal of medicine
A Randomized Trial of Tenecteplase versus Alteplase for Acute Ischemic Stroke
Mark Parsons, M.D., Neil Spratt, M.D., Andrew Bivard, B.Sc., Bruce Campbell, M.D., Kong Chung, M.D., Ferdinand Miteff, M.D., Bill O’Brien, M.D., Christopher Bladin, M.D., Patrick McElduff, Ph.D., Chris Allen, M.D., Grant Bateman, M.D., Geoffrey Donnan, M.D.,
Stephen Davis, M.D., and Christopher Levi, M.D.
Intravenous alteplase is the only approved treatment for acute ischemic stroke. Tenecteplase, a genetically engineered mutant tissue plasminogen activator, is an alternative thrombolytic agent.
In this phase 2B trial, we randomly assigned 75 patients to receive alteplase (0.9 mg per kilogram of body weight) or tenecteplase (0.1 mg per kilogram or 0.25 mg per kilogram) less than 6 hours after the onset of ischemic stroke. To favor the selection of patients most likely to benefit from thrombolytic therapy, the eligibility criteria were a perfusion lesion at least 20% greater than the infarct core on computed tomographic (CT) perfusion imaging at baseline and an associated vessel occlusion on CT angiography. The coprimary end points were the proportion of the perfusion lesion that was reperfused at 24 hours on perfusionweighted magnetic resonance imaging and the extent of clinical improvement at 24 hours as assessed on the National Institutes of Health Stroke Scale (NIHSS, a 42point scale on which higher scores indicate more severe neurologic deficits).
From the Departments of Neurology (M.P., N.S., A.B., K.C., F.M., B.O., C.L.), Clinical Research Design, Information Technology, and Statistical Support (P.M.), and Radiology (C.A., G.B.), John Hunter Hospital–Hunter Medical Re-search Institute, University of Newcastle, Newcastle, NSW; the Department of Neurology, Royal Melbourne Hospital (B.C., S.D.), and Florey Neuroscience In-stitutes (G.D.), University of Melbourne, Melbourne, VIC; and the Department of Neurosciences, Box Hill Hospital–Eastern Health, Monash University (C.B.), Mel-bourne, VIC — all in Australia. Address reprint requests to Dr. Parsons at the De-partment of Neurology, John Hunter Hos-pital, Locked Bag No. 1, Hunter Region Mail Centre, Newcastle, NSW 2310, Aus-tralia, or at firstname.lastname@example.org .gov.au.
N Engl J Med 2012;366:1099-107.
Copyright © 2012 Massachusetts Medical Society.
The three treatment groups each comprised 25 patients. The mean (±SD) NIHSS score at baseline for all patients was 14.4±2.6, and the time to treatment was 2.9±0.8 hours. Together, the two tenecteplase groups had greater reperfusion (P=0.004) and clinical improvement (P<0.001) at 24 hours than the alteplase group. There were no significant betweengroup differences in intracranial bleeding or other serious adverse events. The higher dose of tenecteplase (0.25 mg per kilogram) was superior to the lower dose and to alteplase for all efficacy outcomes, including absence of serious disability at 90 days (in 72% of patients, vs. 40% with alteplase; P = 0.02).
Tenecteplase was associated with significantly better reperfusion and clinical outcomes than alteplase in patients with stroke who were selected on the basis of CT perfusion imaging. (Funded by the Australian National Health and Medical Research Council; Australia New Zealand Clinical Trials Registry number, ACTRN12608000466347.)
n engl j med 366;12 http://www.wenkuxiazai.com march 22, 2012