- Researchers investigated if intravenous tenecteplase before endovascular treatment improves outcomes for ischemic stroke patients in the 4.5 to 24-hour window.
- This phase 3 randomized trial enrolled 391 adults with proximal middle cerebral artery occlusions and salvageable brain tissue at 40 centers.
- Functional independence occurred in 44.2 percent of the tenecteplase group versus 43.2 percent with mechanical thrombectomy alone (p = 0.89).
- The authors concluded that tenecteplase administration before clot retrieval did not significantly improve clinical outcomes compared to endovascular treatment alone.
- These findings suggest that routine thrombolysis may not provide additional benefit for patients presenting late who are eligible for thrombectomy.
Reevaluating Bridging Thrombolysis in the Extended Window
Endovascular treatment has transformed the management of acute ischemic stroke, yet achieving optimal functional recovery remains a challenge for many patients with large vessel occlusions [1, 2]. While intravenous thrombolysis is the standard of care within 4.5 hours of symptom onset, its role as a bridging therapy before mechanical intervention in the extended 4.5 to 24-hour window is less clear [3, 4]. Tenecteplase has emerged as a preferred thrombolytic agent due to its high fibrin specificity and ease of administration, showing potential benefits in recanalization rates compared to alteplase [5, 6]. Recent meta-analyses suggest that while tenecteplase may improve outcomes in patients who do not have access to mechanical thrombectomy, its additive value in the setting of modern endovascular techniques remains a subject of intense clinical debate [7, 8]. A new multicenter phase 3 trial now provides definitive data on whether this pharmacological adjunct improves recovery for late-presenting patients with salvageable brain tissue, answering a critical question for stroke neurologists and emergency physicians.
Trial Design and Patient Selection Criteria
To evaluate the efficacy of pharmacological intervention in the extended stroke window, researchers conducted a multicenter, phase 3, randomized, open-label, blinded end point trial across 40 centers in China. Between January 2024 and July 2025, the study enrolled 391 adult patients with a median age of 68 years (interquartile range, 59 to 75 years), including 155 females (39.6%). Eligible participants presented with an acute ischemic stroke between 4.5 and 24 hours after they were last known to be well, specifically driven by a proximal middle cerebral artery occlusion involving the M1 segment or the proximal M2 segment. Crucially, inclusion required the presence of salvageable brain tissue, defined as viable neurons at risk of infarction that may be saved by reperfusion. The investigators identified this penumbra using computed tomography-perfusion or magnetic resonance-perfusion-diffusion imaging. Patients were enrolled only if they met strict imaging thresholds: an ischemic core volume of less than 70 mL, a mismatch ratio of 1.8 or greater, and a mismatch volume of at least 15 mL. These parameters ensured the study population had a significant volume of threatened but viable tissue relative to the established infarct core. The 391 participants were randomly assigned in a 1:1 ratio to receive either combination therapy or mechanical intervention alone. The intervention group (n = 199) received intravenous tenecteplase at a dose of 0.25 mg/kg, with a maximum total dose of 25 mg, administered prior to endovascular treatment. The control group (n = 192) received endovascular treatment alone, allowing the investigators to isolate the clinical impact of the thrombolytic agent when added to the standard of care for late-presenting large vessel occlusions.
Functional Independence and Primary Efficacy Results
The primary efficacy outcome of the trial was functional independence at 90 days, defined as a score of 0 to 2 on the modified Rankin Scale. This standard clinical measure indicates that a patient has no symptoms or only slight disability, retaining the ability to look after their own affairs without assistance. Among the 199 patients who received intravenous tenecteplase before endovascular treatment, 88 patients (44.2%) achieved functional independence. In comparison, 83 of the 192 patients (43.2%) in the group receiving endovascular treatment alone reached the same level of recovery by the 90-day follow-up. Statistical analysis confirmed that the addition of the thrombolytic agent provided no clinical advantage in this late time window. The adjusted relative rate for functional independence was 1.01 (95% CI, 0.83 to 1.24; P = .89), indicating no significant difference between the two treatment arms. Furthermore, the risk difference for functional independence was 0.99% (95% CI, -8.84% to 10.83%), a narrow margin that underscores the lack of superiority for the bridging therapy. For practicing physicians, these findings demonstrate that administering tenecteplase prior to mechanical thrombectomy for proximal middle cerebral artery occlusions identified between 4.5 and 24 hours after onset does not improve the likelihood of a favorable functional outcome, suggesting that direct-to-angio approaches are sufficient.
Safety Profile and Hemorrhagic Risk
The safety analysis focused on mortality and hemorrhagic complications to determine if the addition of tenecteplase introduced significant risks without corresponding benefits. At the 90-day follow-up, the researchers found that mortality was 12.7% (25 of 197 patients) in the group receiving tenecteplase before endovascular treatment. This was numerically similar to the mortality rate of 14.2% (27 of 190 patients) observed in the group receiving endovascular treatment alone. While these figures suggest that the thrombolytic agent did not increase the overall risk of death, the lack of a significant difference in survival aligns with the primary efficacy results showing no functional advantage for the bridging approach. Regarding safety concerns specific to thrombolysis, the study monitored the incidence of symptomatic intracranial hemorrhage, defined as a brain bleed associated with clinical worsening. The rate of symptomatic intracranial hemorrhage within 36 hours was 5.1% (10 of 197 patients) in the tenecteplase group, compared to 2.6% (5 of 190 patients) in the endovascular treatment alone group. Although the tenecteplase arm showed a higher numerical incidence of these early hemorrhagic events, the overall clinical outcomes remained similar between the two cohorts. For clinicians managing patients at centers capable of performing mechanical thrombectomy, these data provide clear guidance: administering tenecteplase between 4.5 and 24 hours after stroke onset provides no additional benefit and may increase the risk of early symptomatic bleeding. Consequently, the findings strongly support proceeding directly to endovascular treatment in this extended time window when proximal middle cerebral artery occlusions are identified.
References
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