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Tenecteplase for Stroke at 4.5 to 24 Hours with Perfusion-Imaging Selection.

Gregory W Albers1, Mouhammad Jumaa1, Barbara Purdon1

  • 1From 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.).

The New England Journal of Medicine
|February 8, 2024
PubMed
Summary

Tenecteplase did not improve outcomes for ischemic stroke patients treated between 4.5 and 24 hours, even with thrombectomy. The study found no significant difference in clinical outcomes or hemorrhage rates compared to placebo.

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Area of Science:

  • Neurology
  • Cardiovascular Medicine
  • Pharmacology

Background:

  • Thrombolytic agents like tenecteplase are standard for ischemic stroke within 4.5 hours.
  • Limited data exists on tenecteplase efficacy beyond this 4.5-hour window.

Purpose of the Study:

  • To evaluate the effectiveness and safety of tenecteplase compared to placebo in ischemic stroke patients presenting 4.5 to 24 hours after symptom onset.
  • To assess clinical outcomes using the modified Rankin scale and safety outcomes including mortality and hemorrhage.

Main Methods:

  • A multicenter, double-blind, randomized, placebo-controlled trial.
  • Included patients with ischemic stroke, middle cerebral artery or internal carotid artery occlusion, and salvageable tissue on perfusion imaging.
  • Administered tenecteplase (0.25 mg/kg) or placebo 4.5-24 hours after last known well time.

Main Results:

  • 458 patients were enrolled; 77.3% underwent thrombectomy.
  • Median modified Rankin scale score at 90 days was 3 in both tenecteplase and placebo groups (OR 1.13, P=0.45).
  • 90-day mortality was 19.7% with tenecteplase vs. 18.2% with placebo; symptomatic intracranial hemorrhage was 3.2% vs. 2.3%.

Conclusions:

  • Tenecteplase initiated 4.5-24 hours post-stroke did not improve clinical outcomes compared to placebo in patients with major artery occlusions, many of whom received thrombectomy.
  • The incidence of symptomatic intracerebral hemorrhage was similar between tenecteplase and placebo groups.