SOURCE: Albers GW, Jumaa M, Purdon B, et al; TIMELESS Investigators. Tenecteplase for stroke at 4.5 to 24 hours with perfusion-imaging selection. N Engl J Med 2024;390:701-711.
Standard therapy for acute ischemic stroke is intravenous thrombolysis within 4.5 hours from onset of symptoms. Alteplase has been the standard medication, but in recent years, tenecteplase has supplanted alteplase because of its ease of administration as a single intravenous bolus and lower cost. In multiple studies, tenecteplase has been shown to be noninferior to alteplase, and it has been gradually replacing alteplase in multiple stroke centers throughout the world. The use of advanced imaging with computed tomography (CT) perfusion or perfusion-diffusion magnetic resonance imaging (MRI) has allowed us to identify patients with viable brain tissue at later times who might benefit from treatment. Therefore, the TIMELESS study was developed to evaluate the effect of treatment with tenecteplase 4.5 to 24 hours after stroke onset in patients with large artery occlusion who subsequently would go on to endovascular thrombectomy.
TIMELESS was a multicenter, double-blind, randomized and placebo-controlled trial of patients with acute ischemic stroke comparing treatment with tenecteplase (0.25 mg/kg) with placebo, administered after 4.5 hours until 24 hours after onset of symptoms. The study was restricted to patients who had large artery occlusion of the internal carotid or middle cerebral artery and viable and salvageable brain tissue based on advanced perfusion imaging with CT or MRI.
A total of 458 patients were enrolled, and 77.3% of them subsequently underwent an endovascular thrombectomy. Of the enrollees, 228 patients were assigned to receive tenecteplase and the remaining patients received placebo. The median time from last known well to randomization was 12 hours in the tenecteplase group and 13 hours in the placebo group. During follow-up at 90 days, the median score on the modified Rankin Scale was 3 in each group. There was no significant difference between the groups on either outcome or mortality (19.7% vs. 18.2%). The incidence of symptomatic intracranial hemorrhage was 3.2% and 2.3%, respectively.
In conclusion, treatment with tenecteplase initiated between 4.5 to 24 hours after stroke onset followed by endovascular thrombectomy did not result in better clinical outcomes than in patients treated with placebo. Adverse effects and complications were similar in the two groups.
