• Campbell Bruce C V BCV 0000-0003-3632-9433 From the Departments of Medicine and Neurology, Melbourne Brain Centre (B.C.V.C., N.Y., B.Y., T.Y.W., D.G.S, Peter J Mitchell, Leonid Churilov, Nawaf Yassi, Timothy J Kleinig, Richard J Dowling, Bernard Yan, Steven J Bush, Helen M Dewey, Vincent Thijs, Rebecca Scroop, Marion Simpson, Mark Brooks, Hamed Asadi, Teddy Y Wu, Darshan G Shah, Tissa Wijeratne, Timothy Ang, Ferdinand Miteff, Christopher R Levi, Edrich Rodrigues, Henry Zhao, Patrick Salvaris, Carlos Garcia-Esperon, Peter Bailey, Henry Rice, Laetitia de Villiers, Helen Brown, Kendal Redmond, David Leggett, John N Fink, Wayne Collecutt, Andrew A Wong, Claire Muller, Alan Coulthard, Ken Mitchell, John Clouston, Kate Mahady, Deborah Field, Henry Ma, Thanh G Phan, Winston Chong, Ronil V Chandra, Lee-Anne Slater, Martin Krause, Timothy J Harrington, Kenneth C Faulder, Brendan S Steinfort, Christopher F Bladin, Gagan Sharma, Patricia M Desmond, Mark W Parsons, Geoffrey A Donnan, Stephen M Davis, and EXTEND-IA TNK Investigators.
• From the Departments of Medicine and Neurology, Melbourne Brain Centre (B.C.V.C., N.Y., B.Y., T.Y.W., D.G.S., E.R., H.Z., P.S., G.S., M.W.P., S.M.D.), and the Department of Radiology (P.J.M., R.J.D., S.J.B., P.M.D.), Royal Melbourne Hospital, and the Florey Institute of Neuroscience and Mental Health (L.C., N.Y., V.T., H.A., H.M., C.F.B., G.A.D.), University of Melbourne, Parkville, VIC, the Departments of Neurology (T.J.K.) and Radiology (R.S.), Royal Adelaide Hospital, and the Department of Neurology, Lyell McEwin Hospital (D.F.), Adelaide, SA, the Department of Neurosciences, Eastern Health and Eastern Health Clinical School (H.M.D., C.F.B.), and the Departments of Neurology (H.M., T.G.P.) and Radiology (W. Chong, R.V.C., L.-A.S.), Monash Medical Centre, Monash University, Clayton, VIC, the Departments of Neurology (V.T., M.S.) and Radiology (M.B., H.A.), Austin Hospital, Austin Health, Heidelberg, VIC, School of Medicine, Faculty of Health, Deakin University, Melbourne, VIC (H.A.), and the Departments of Medicine and Neurology, Melbourne Medical School, University of Melbourne and Western Health, Sunshine Hospital, St. Albans, VIC (T.W.), the Departments of Neurology (D.G.S., H.B.) and Radiology (K.R., D.L.), Princess Alexandra Hospital, and the Departments of Neurology (A.A.W., C.M.) and Radiology (A.C., K. Mitchell, J.C., K. Mahady), Royal Brisbane and Women's Hospital and the University of Queensland, Brisbane, the Departments of Neurology (P.B.) and Radiology (H.R., L.V.), Gold Coast University Hospital, Southport, QLD, and the Department of Neurology, Priority Research Centre for Brain and Mental Health Research, John Hunter Hospital, University of Newcastle, Newcastle, NSW (T.A., F.M., C.R.L., C.G.-E., M.W.P.), the Department of Neurology, Royal North Shore Hospital and Kolling Institute, University of Sydney (M.K.), and the Department of Radiology, Royal North Shore Hospital (T.J.H., K.C.F., B.S.S.), St. Leonards, and the Department of Radiology, Westmead Hospital, Sydney (T.J.H., K.C.F., B.S.S.) - all in Australia; and the Departments of Neurology (T.Y.W., J.N.F.) and Radiology (W. Collecutt), Christchurch Hospital, Christchurch, New Zealand.
• N. Engl. J. Med. 2018 Apr 26; 378 (17): 1573-1582.

BackgroundIntravenous infusion of alteplase is used for thrombolysis before endovascular thrombectomy for ischemic stroke. Tenecteplase, which is more fibrin-specific and has longer activity than alteplase, is given as a bolus and may increase the incidence of vascular reperfusion.MethodsWe randomly assigned patients with ischemic stroke who had occlusion of the internal carotid, basilar, or middle cerebral artery and who were eligible to undergo thrombectomy to receive tenecteplase (at a dose of 0.25 mg per kilogram of body weight; maximum dose, 25 mg) or alteplase (at a dose of 0.9 mg per kilogram; maximum dose, 90 mg) within 4.5 hours after symptom onset. The primary outcome was reperfusion of greater than 50% of the involved ischemic territory or an absence of retrievable thrombus at the time of the initial angiographic assessment. Noninferiority of tenecteplase was tested, followed by superiority. Secondary outcomes included the modified Rankin scale score (on a scale from 0 [no neurologic deficit] to 6 [death]) at 90 days. Safety outcomes were death and symptomatic intracerebral hemorrhage.ResultsOf 202 patients enrolled, 101 were assigned to receive tenecteplase and 101 to receive alteplase. The primary outcome occurred in 22% of the patients treated with tenecteplase versus 10% of those treated with alteplase (incidence difference, 12 percentage points; 95% confidence interval [CI], 2 to 21; incidence ratio, 2.2; 95% CI, 1.1 to 4.4; P=0.002 for noninferiority; P=0.03 for superiority). Tenecteplase resulted in a better 90-day functional outcome than alteplase (median modified Rankin scale score, 2 vs. 3; common odds ratio, 1.7; 95% CI, 1.0 to 2.8; P=0.04). Symptomatic intracerebral hemorrhage occurred in 1% of the patients in each group.ConclusionsTenecteplase before thrombectomy was associated with a higher incidence of reperfusion and better functional outcome than alteplase among patients with ischemic stroke treated within 4.5 hours after symptom onset. (Funded by the National Health and Medical Research Council of Australia and others; EXTEND-IA TNK ClinicalTrials.gov number, NCT02388061 .).

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