Tenecteplase before EVT shows no functional benefit over EVT alone in late window stroke

This phase 3 randomized clinical trial evaluated the efficacy and safety of intravenous tenecteplase administered before endovascular thrombectomy (EVT) in adults with acute ischemic stroke presenting 4.5 to 24 hours after last known well. Eligible patients had a proximal middle cerebral artery (MCA-M1 or proximal M2) occlusion with salvageable brain tissue, defined by an ischemic core volume <70 mL, mismatch ratio ≥1.8, and mismatch volume ≥15 mL. The study enrolled 391 patients across 40 centers in China, randomizing them to receive either tenecteplase (0.25 mg/kg, max 25 mg) followed by EVT or EVT alone.

The primary outcome was functional independence, defined as a modified Rankin Scale score of 0 to 2 at 90 days. Results showed no significant difference between groups: 44.2% in the tenecteplase-before-EVT group achieved functional independence versus 43.2% in the EVT-alone group. The adjusted relative rate was 1.01 (95% CI, 0.83–1.24; P = .89), indicating no improvement. Absolute numbers were 88/199 versus 83/192, respectively.

Secondary outcomes included mortality and symptomatic intracranial hemorrhage (sICH). Mortality within 90 days was 12.7% in the tenecteplase group versus 14.2% in the EVT-alone group (25/197 vs. 27/190). sICH within 36 hours occurred in 5.1% of the tenecteplase group versus 2.6% of the EVT-alone group (10/197 vs. 5/190). These differences were not statistically tested in the provided data, but the higher sICH rate with tenecteplase warrants attention.

Safety findings highlighted symptomatic intracranial hemorrhage and death as adverse events. The study did not report discontinuations or overall tolerability. Limitations were not specified in the input, but potential constraints include the single-country setting, which may limit generalizability, and the absence of reported funding or conflicts.

Practice relevance is clear: for patients presenting to EVT-capable centers 4.5 to 24 hours after stroke onset with proximal MCA occlusion, intravenous tenecteplase before EVT did not improve clinical outcomes compared to EVT alone. This suggests that in this specific late-window population, the added thrombolytic may not be beneficial and could increase hemorrhage risk.

Causality and certainty notes were not reported, so the evidence should be interpreted with caution. The trial's phase 3 design and randomized methodology support internal validity, but external applicability may vary. Clinicians should weigh the lack of benefit against the potential for increased sICH when considering tenecteplase in this context.

In summary, this trial provides evidence that tenecteplase before EVT does not enhance functional independence in late-window ischemic stroke patients with salvageable tissue. The findings support current guidelines that emphasize EVT as the primary intervention in this population, with thrombolysis reserved for earlier windows or specific scenarios.