• Gregory W Albers, Mouhammad Jumaa, Barbara Purdon, Syed F Zaidi, Christopher Streib, Ashfaq Shuaib, Navdeep Sangha, Minjee Kim, Michael T Froehler, Neil E Schwartz, Wayne M Clark, Charles E Kircher, Ming Yang, Lori Massaro, Xiao-Yu Lu, Gregory A Rippon, Joseph P Broderick, Ken Butcher, Maarten G Lansberg, David S Liebeskind, Amre Nouh, Lee H Schwamm, CampbellBruce C VBCVFrom Stanford Stroke Center, Department of Neurology and Neurological Sciences, Stanford University, Palo Alto (G.W.A., N.E.S., M.G.L.), Genentech, South San Francisco (B.P., M.Y., L.M., X.-Y.L., G.A.R.), and the Department of Neurolog, and TIMELESS Investigators.
• From Stanford Stroke Center, Department of Neurology and Neurological Sciences, Stanford University, Palo Alto (G.W.A., N.E.S., M.G.L.), Genentech, South San Francisco (B.P., M.Y., L.M., X.-Y.L., G.A.R.), and the Department of Neurology, Southern California Permanente Medical Group, Los Angeles Medical Center (N.S.), and the Department of Neurology, University of California, Los Angeles (D.S.L.), Los Angeles - all in California; the Department of Neurology, ProMedica Toledo Hospital, University of Toledo, Toledo (M.J., S.F.Z.), and the Department of Emergency Medicine (C.E.K.) and the Department of Neurology and Rehabilitation Medicine, University of Cincinnati Gardner Neuroscience Institute (J.P.B.), College of Medicine, University of Cincinnati, Cincinnati - both in Ohio; the Department of Neurology, University of Minnesota, Minneapolis (C.S.); the Department of Medicine, University of Alberta, Edmonton, Canada (A.S.); the Department of Neurology, Feinberg School of Medicine, Northwestern University, Chicago (M.K.); Vanderbilt Cerebrovascular Program, Vanderbilt University Medical Center, Nashville (M.T.F.); Oregon Stroke Center, Oregon Health and Science University, Portland (W.M.C.); the School of Medicine, University of New South Wales, Sydney (K.B.), and the Department of Medicine and Neurology, Melbourne Brain Centre at the Royal Melbourne Hospital, University of Melbourne, Parkville, VIC (B.C.V.C.) - both in Australia; the Department of Neurology, Cleveland Clinic Florida, Weston Hospital, Weston (A.N.); the Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston (L.H.S.); and the Department of Neurology, Yale School of Medicine, New Haven, CT (L.H.S.).
• N. Engl. J. Med. 2024 Feb 22; 390 (8): 701711701-711.

BackgroundThrombolytic agents, including tenecteplase, are generally used within 4.5 hours after the onset of stroke symptoms. Information on whether tenecteplase confers benefit beyond 4.5 hours is limited.MethodsWe conducted a multicenter, double-blind, randomized, placebo-controlled trial involving patients with ischemic stroke to compare tenecteplase (0.25 mg per kilogram of body weight, up to 25 mg) with placebo administered 4.5 to 24 hours after the time that the patient was last known to be well. Patients had to have evidence of occlusion of the middle cerebral artery or internal carotid artery and salvageable tissue as determined on perfusion imaging. The primary outcome was the ordinal score on the modified Rankin scale (range, 0 to 6, with higher scores indicating greater disability and a score of 6 indicating death) at day 90. Safety outcomes included death and symptomatic intracranial hemorrhage.ResultsThe trial enrolled 458 patients, 77.3% of whom subsequently underwent thrombectomy; 228 patients were assigned to receive tenecteplase, and 230 to receive placebo. The median time between the time the patient was last known to be well and randomization was approximately 12 hours in the tenecteplase group and approximately 13 hours in the placebo group. The median score on the modified Rankin scale at 90 days was 3 in each group. The adjusted common odds ratio for the distribution of scores on the modified Rankin scale at 90 days for tenecteplase as compared with placebo was 1.13 (95% confidence interval, 0.82 to 1.57; P = 0.45). In the safety population, mortality at 90 days was 19.7% in the tenecteplase group and 18.2% in the placebo group, and the incidence of symptomatic intracranial hemorrhage was 3.2% and 2.3%, respectively.ConclusionsTenecteplase therapy that was initiated 4.5 to 24 hours after stroke onset in patients with occlusions of the middle cerebral artery or internal carotid artery, most of whom had undergone endovascular thrombectomy, did not result in better clinical outcomes than those with placebo. The incidence of symptomatic intracerebral hemorrhage was similar in the two groups. (Funded by Genentech; TIMELESS ClinicalTrials.gov number, NCT03785678.).Copyright © 2024 Massachusetts Medical Society.

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