Intravenous tenecteplase improves functional outcomes but increases hemorrhage risk in non-large vessel occlusion acute ischemic stroke.

This study was a randomized, open-label, blinded end-point clinical trial conducted across 48 centers in China. The population consisted of 570 patients randomized, with 566 included in the primary analysis. All participants had non-large vessel occlusion acute ischemic stroke and evidence of potentially salvageable tissue determined by perfusion imaging. Patients presented within 4.5 to 24 hours of the time they were last seen well. The intervention group received intravenous tenecteplase at a dose of 0.25 mg/kg, with a maximum dose of 25 mg. The comparator group received standard medical treatment. The primary outcome was excellent functional outcome, defined as a score of 0 or 1 on the modified Rankin Scale at 90 days. Follow-up occurred at 90 days.

The primary results demonstrated a greater likelihood of excellent functional outcome in the tenecteplase group compared to the control group. Specifically, 123 of 282 patients (43.6%) in the tenecteplase group achieved this outcome versus 97 of 284 (34.2%) in the control group. The effect size was a risk ratio of 1.28, with a 95% confidence interval of 1.04-1.57 and a P value of .02.

Key secondary outcomes included symptomatic intracranial hemorrhage within 36 hours and mortality within 90 days. Symptomatic intracranial hemorrhage occurred in 2.8% of patients in the tenecteplase group versus 0% in the control group. The risk difference was 2.85%, with a 95% confidence interval of 1.16%-5.54% and a P value of .004. Mortality at 90 days was 5.0% in the tenecteplase group versus 3.2% in the control group. The risk ratio for mortality was 1.57, with a 95% confidence interval of 0.69-3.57 and a P value of .28, indicating the difference was not statistically significant.

Safety and tolerability findings focused on adverse events. The primary safety concern was symptomatic intracranial hemorrhage within 36 hours. Rates of serious adverse events, discontinuations, and overall tolerability were not reported in the provided data. The increased rate of symptomatic intracranial hemorrhage represents a significant safety signal that must be considered alongside the functional benefits.

This study addresses the therapeutic area of acute ischemic stroke thrombolysis, specifically extending the treatment window to 24 hours for selected patients with salvageable tissue. While prior landmark studies have established the efficacy of alteplase within 3 to 4.5 hours, this trial explores the utility of tenecteplase in a broader time frame. The results suggest that tenecteplase may offer a therapeutic advantage over standard care in this specific extended window, though direct comparisons to alteplase data are limited by the study design and specific patient selection criteria regarding salvageable tissue.

Key methodological limitations include the open-label nature of the trial, which may introduce bias in outcome assessment despite the blinded end-point design. The study was conducted exclusively in China, which may limit generalizability to other populations or healthcare settings. Additionally, the lack of reported data on serious adverse events, discontinuations, and overall tolerability restricts a full safety profile assessment. The observational determination of salvageable tissue via perfusion imaging introduces potential variability in patient selection that could influence outcomes.

Clinical implications suggest that intravenous tenecteplase may be a viable option for patients with non-large vessel occlusion stroke presenting between 4.5 and 24 hours who have salvageable brain tissue. However, the increased risk of symptomatic intracranial hemorrhage requires careful patient selection and informed consent. Practitioners should consider the absolute risk increase in hemorrhage when deciding on thrombolysis. The non-significant difference in mortality suggests that the primary benefit is functional recovery rather than survival.

Several questions remain unanswered. The long-term safety profile beyond 36 hours requires further investigation. The generalizability of these findings to patients in different geographic regions or with different comorbidity profiles is uncertain. Additionally, the comparative efficacy of tenecteplase versus alteplase in this extended time window has not been directly addressed in this study. Further research is needed to optimize patient selection criteria and refine the risk-benefit analysis for this intervention.