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Xiong Y, Campbell BCV, Schwamm LH, et al. Tenecteplase for Ischemic Stroke at 4.5 to 24 Hours without Thrombectomy. N Engl J Med. 2024 Jul 18;391(3):203-212. doi: 10.1056/NEJMoa2402980. Epub 2024 Jun 14. (Original study)
Abstract

BACKGROUND: Tenecteplase is an effective thrombolytic agent for eligible patients with stroke who are treated within 4.5 hours after the onset of stroke. However, data regarding the effectiveness of tenecteplase beyond 4.5 hours are limited.

METHODS: In a trial conducted in China, we randomly assigned patients with large-vessel occlusion of the middle cerebral artery or internal carotid artery who had salvageable brain tissue as identified on perfusion imaging and who did not have access to endovascular thrombectomy to receive tenecteplase (at a dose of 0.25 mg per kilogram of body weight; maximum dose, 25 mg) or standard medical treatment 4.5 to 24 hours after the time that the patient was last known to be well (including after stroke on awakening and unwitnessed stroke). The primary outcome was the absence of disability, which was defined as a score of 0 or 1 on the modified Rankin scale (range, 0 to 6, with higher scores indicating greater disability), at day 90. The key safety outcomes were symptomatic intracranial hemorrhage and death.

RESULTS: A total of 516 patients were enrolled; 264 were randomly assigned to receive tenecteplase and 252 to receive standard medical treatment. Less than 2% of the patients (4 in the tenecteplase group and 5 in the standard-treatment group) underwent rescue endovascular thrombectomy. Treatment with tenecteplase resulted in a higher percentage of patients with a modified Rankin scale score of 0 or 1 at 90 days than standard medical treatment (33.0% vs. 24.2%; relative rate, 1.37; 95% confidence interval, 1.04 to 1.81; P = 0.03). Mortality at 90 days was 13.3% with tenecteplase and 13.1% with standard medical treatment, and the incidence of symptomatic intracranial hemorrhage within 36 hours after treatment was 3.0% and 0.8%, respectively.

CONCLUSIONS: In this trial involving Chinese patients with ischemic stroke due to large-vessel occlusion, most of whom did not undergo endovascular thrombectomy, treatment with tenecteplase administered 4.5 to 24 hours after stroke onset resulted in less disability and similar survival as compared with standard medical treatment, and the incidence of symptomatic intracranial hemorrhage appeared to be higher. (Funded by the National Natural Science Foundation of China and others; TRACE-III ClinicalTrials.gov number, NCT05141305.).

Ratings
Discipline Area Score
Hospital Doctor/Hospitalists 6 / 7
Internal Medicine 6 / 7
Neurology 6 / 7
Comments from MORE raters

Hospital Doctor/Hospitalists rater

Difficult risk-benefit assessment. Overall, more "good stroke outcomes" with treatment, but also more intracranial hemorrhage with probably worse outcomes for those patients.

Neurology rater

This study took patients with ischemic stroke with moderate stroke severity beyond 4.5 hours (selected by imaging criteria) and randomized to tenecteplase vs standard treatment and demonstrated efficacy in reducing disability. This shows that tenectplase is efficacious beyond 4.5 hours, similar to what the EXTEND study showed for alteplase. The study, however, systematically excluded sites that could perform endovascular therapy. Although the efficacy is shown, it has limited practical consequence because the impact of mechanical thrombectomy is larger. In situations or patients for which thrombectomy is not an option, however, this shows the underlying benefit of thrombolytic recanalization.
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