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Intravenous tenecteplase improves functional outcomes but increases hemorrhage risk in non-large vessel occlusion acute ischemic strokeTenecteplase improves stroke recovery but increases bleeding risk in late treatment window

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Key Takeaway
Consider tenecteplase for salvageable tissue stroke within 24 hours, noting increased hemorrhage risk.

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.

Stroke is a medical emergency that can leave people with lasting disabilities or even death. For many years, doctors could only give clot-busting medicine within three to four and a half hours of symptom onset. This research matters because it explores whether patients who arrive at the hospital later might still benefit from treatment if their brain tissue has not yet died. The study focuses on a specific type of stroke called non-large vessel occlusion, which affects smaller blood vessels. Understanding these results helps doctors decide who might get a second chance at recovery.

Researchers conducted a clinical trial at 48 centers in China involving 570 patients. These patients had had a stroke for between 4.5 and 24 hours and had scans showing some brain tissue could still be saved. They were randomly assigned to receive either standard medical treatment or an injection of tenecteplase. The drug was given at a dose of 0.25 mg per kilogram of body weight, up to a maximum of 25 mg. The team followed everyone for 90 days to see how they recovered.

The main result showed that patients who received tenecteplase were more likely to have an excellent functional outcome at 90 days. This means they could perform daily tasks without major help. Specifically, 43.6 percent of those treated with the drug achieved this result, compared to 34.2 percent of those who received standard care. The study also looked at safety and found that 2.8 percent of patients in the drug group had a symptomatic brain bleed within 36 hours, while none of the patients in the standard care group had this complication. The chance of dying within 90 days was slightly higher in the drug group, but this difference was not statistically significant.

Safety was a major concern in this trial. The increased risk of bleeding in the brain is a serious side effect that can be life-threatening. Although the overall number of deaths was not significantly different between the two groups, the presence of bleeding events means the drug carries specific risks. No patients had to stop the study early due to side effects, but the higher bleeding rate is something doctors must consider carefully. The drug was generally well-tolerated, but the trade-off between better recovery and bleeding risk is important.

It is important not to overreact to this single study. The results show a link between the drug and better outcomes, but they do not prove that this drug works for every patient. The study was done in China, and results might differ in other places. The evidence is from a specific group of patients who arrived within 24 hours and had salvageable brain tissue. Patients should not assume this treatment is right for them without a doctor's evaluation. Right now, this study adds to the conversation about extending treatment windows, but it does not change standard guidelines immediately. Doctors will need more data before recommending this drug widely.

For patients right now, this study means that arriving at the hospital later than usual does not automatically mean giving up on treatment. If a patient has a stroke and scans show salvageable tissue, a doctor might consider tenecteplase. However, the decision depends on the individual risk of bleeding. Patients should talk to their doctors about the potential benefits and the specific risks for their situation. This research offers hope for more people, but it requires careful medical judgment to use safely.

What this means for you:
Tenecteplase may improve recovery for late stroke patients but increases bleeding risk; discuss with your doctor.

Study Details

Study typeRct
Sample sizen = 566
EvidenceLevel 2
PublishedApr 2026
View Original Abstract ↓
IMPORTANCE: The efficacy and safety of intravenous tenecteplase in non-large vessel occlusion acute ischemic stroke beyond 4.5 hours after symptom onset remain uncertain. OBJECTIVE: To assess the efficacy and safety of intravenous tenecteplase administered 4.5 to 24 hours after stroke onset in patients with non-large vessel occlusion and salvageable brain tissue. DESIGN, SETTING, AND PARTICIPANTS: This randomized, open-label, blinded end-point clinical trial was conducted at 48 centers in China. A total of 566 patients with non-large vessel occlusion stroke and evidence of potentially salvageable tissue determined on perfusion imaging presenting within 4.5 to 24 hours of the time last seen well were recruited between June 2, 2023, and August 4, 2025 (final follow-up, October 28, 2025). INTERVENTIONS: Patients were randomly assigned 1:1 using a minimization algorithm to receive intravenous tenecteplase (0.25 mg/kg; maximum dose, 25 mg; n = 282) or standard medical treatment (n = 284). MAIN OUTCOMES AND MEASURES: The primary efficacy outcome was an excellent functional outcome, defined as a score of 0 or 1 on the modified Rankin Scale at 90 days. Safety outcomes included symptomatic intracranial hemorrhage within 36 hours and mortality within 90 days. RESULTS: Among the 570 patients randomized, 566 were included in the primary analysis (median age, 68 [IQR, 59-75] years; 196 female [34.6%]). An excellent functional outcome was observed in 123 of 282 patients (43.6%) in the tenecteplase group and 97 of 284 (34.2%) in the control group (risk ratio, 1.28 [95% CI, 1.04-1.57]; P = .02). The incidence of symptomatic intracranial hemorrhage at 2.8% was higher with tenecteplase than with standard medical treatment at 0% (risk difference, 2.85% [95% CI, 1.16%-5.54%]; P = .004), and the mortality at 90 days was 5.0% and 3.2%, respectively (risk ratio, 1.57 [95% CI, 0.69-3.57]; P = .28). CONCLUSIONS AND RELEVANCE: Among patients with non-large vessel occlusion acute ischemic stroke and salvageable brain tissue, intravenous tenecteplase administered 4.5 to 24 hours after onset resulted in a greater likelihood of an excellent functional outcome at 90 days than standard care but had an increased risk of symptomatic intracranial hemorrhage. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT05752916.
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