TIMELESS Trial of Late Window Stroke Thrombolysis

TIMELESS trial evaluated the role of thrombolysis with tenecteplase in patients with ischemic stroke due to large artery occlusion having favourable perfusion imaging, beyond 4.5 hours of symptom onset [1]. No improvement in neurologic outcomes were noted and risk of hemorrhagic conversion was similar to placebo. Thrombolysis is generally considered in ischemic stroke within 4.5 hours of onset of symptoms. TIMELESS trial involved the extended window under consideration from 4.5 hours to 24 hours after the time that the patient was last known to be well. Other inclusion criteria needed were evidence of occlusion of middle cerebral artery or internal carotid artery and salavageable tissue as determined by perfusion imaging.

It was a multicenter, double blind, randomized placebo controlled trial. 458 patients were enrolled, of which 77.3% subsequently underwent endovascular thrombectomy. Median modified Rankin score was 3 in each group at 90 days. 90 day mortality was 19.7% in the tenecteplase group and 18.2% in the placebo group. Endovascular thrombectomy was done at a median of 16 minutes after treatment with tenecteplase or placebo in this trial. Thrombectomy has been shown to be of greater benefit when combined with thrombolytic therapy within 4.5 hours of onset of symptoms.