TIMELESS
Trial question
What is the effect of tenecteplase therapy initiated 4.5-24 hours after stroke onset in patients with an occlusion of the middle cerebral artery or internal carotid artery?
Study design
Multi-center
Double blinded
RCT
Population
Characteristics of study participants
53.0% female
47.0% male
N = 458
458 patients (245 female, 213 male).
Inclusion criteria: patients with ischemic stroke and evidence of occlusion of the middle cerebral artery or internal carotid artery and salvageable tissue as determined on perfusion imaging.
Key exclusion criteria: active internal bleeding; known bleeding diathesis; known hypersensitivity or allergy to tenecteplase; intracranial neoplasm; pregnancy.
Interventions
N=228 tenecteplase (at a dose of 0.25 mg/kg of body weight, maximum dose 25 mg, administered 4.5-24 hours after stroke onset).
N=230 placebo (matching placebo administered 4.5-24 hours after stroke onset).
Primary outcome
Median modified Rankin Scale score at day 90
3 points
3 points
3.0 points
2.3 points
1.5 points
0.8 points
0.0 points
Tenecteplase
Placebo
No significant
difference ↔
No significant difference in median mRS score at day 90 (3 points vs. 3 points; OR 1.13, 95% CI 0.82 to 1.57).
Secondary outcomes
No significant difference in functional independence at day 90 (46% vs. 42.4%; OR 1.18, 95% CI 0.8 to 1.74).
Significant increase in recanalization at 24 hours (76.7% vs. 63.9%; OR 1.89, 95% CI 1.21 to 2.95).
No significant difference in reperfusion at the conclusion of endovascular thrombectomy (89.1% vs. 85.4%; OR 1.42, 95% CI 0.75 to 2.67).
Safety outcomes
No significant differences in death, symptomatic ICH, parenchymal hematoma.
Conclusion
In patients with ischemic stroke and evidence of occlusion of the middle cerebral artery or internal carotid artery and salvageable tissue as determined on perfusion imaging, tenecteplase was not superior to placebo with respect to median mRS score at day 90.
Reference
Gregory W Albers, Mouhammad Jumaa, Barbara Purdon et al. Tenecteplase for Stroke at 4.5 to 24 Hours with Perfusion-Imaging Selection. N Engl J Med. 2024 Feb 22;390(8):701-711.
Open reference URL