Home›Neurology› Network meta-analysis compares alteplase, tenecteplase, and JX10 for acute ischemic stroke treatment outcomes
Network meta-analysis compares alteplase, tenecteplase, and JX10 for acute ischemic stroke treatment outcomesNew analysis compares three clot-busting drugs for stroke patients treated up to twenty-four hours after symptoms start
Frontiers in MedicinePublished May 29, 2026DOI ↗Editorial oversight: Dr. Ji-eun Park, MD · Brain, Mind & Pain
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Key Takeaway
Alteplase improves functional independence but increases bleeding risk; JX10 and tenecteplase require further validation in larger trials.
A comprehensive network meta-analysis examined the efficacy of intravenous thrombolytic agents, including alteplase, tenecteplase, and JX10, for patients with acute ischemic stroke presenting between 4.5 and 24 hours after symptom onset. The study analyzed data from 2,409 patients to determine the impact on functional outcomes and safety profiles at 90 days.
Results indicated that alteplase significantly increased the proportion of functionally independent patients compared with standard of care. Tenecteplase and JX10 demonstrated trends toward improvement but did not reach statistical significance. Alteplase also ranked first for reperfusion at 24 hours, showing superior performance over standard care.
Safety analysis revealed that alteplase significantly increased the risk of symptomatic intracranial hemorrhage compared with standard of care. JX10 exhibited the highest risk of bleeding among the tested interventions. No statistically significant differences were observed regarding mortality at 90 days across the different treatment groups.
The authors caution that JX10 evidence is currently hypothesis-generating only, and clinical efficacy remains unestablished. Therapeutic advantages of tenecteplase have not been fully demonstrated. Clinical decision-making requires individualized consideration based on imaging screening, bleeding risk assessment, and patient preference. Urgent need for larger-scale, rigorously designed head-to-head randomized controlled trials exists.
Doctors studied over two thousand four hundred patients who had a stroke and were treated with clot-busting medicine. The review looked at three options: the standard drug, a newer drug called tenecteplase, and an even newer option called JX10. The main goal was to see which treatment helped the most people regain their ability to walk and live independently after ninety days.
The standard drug worked best for getting blood flowing again quickly. It also helped more patients recover their function compared to doing nothing or using a fake treatment. However, this standard drug also caused a much higher risk of serious bleeding inside the brain compared to usual care. The newer drugs showed some good signs of helping, but the data was not strong enough to say they were definitely better yet.
No study showed that one drug killed more people than the others. Because the evidence for the new options is not yet strong, doctors must carefully weigh the benefits against the risks. Each patient is different, so the best choice depends on their specific scan results and bleeding risk. More large studies are needed to prove if the new drugs are truly safe and effective before they are widely used.
What this means for you:
One standard drug helped more patients recover, while new options need more testing to prove they are safe and effective for everyone.
ObjectiveThis study aims to systematically evaluate the efficacy and safety of different intravenous thrombolytic agents in patients with acute ischemic stroke (IS) who present between 4.5 and 24 h after symptom onset. A network meta-analysis was conducted to compare the available treatments and provide evidence to support clinical decision-making and inform updates to clinical guidelines.MethodsA systematic search was conducted in PubMed, Embase, the Cochrane Library, and Web of Science, covering the period from the inception of each database to February 1, 2026. Randomized controlled trials (RCTs) comparing different intravenous thrombolytic regimens within the extended time window were included. Primary outcomes included a modified Rankin Scale score of 0–1 at 90 days, mRS 0–2 at 90 days, improvement in the National Institutes of Health Stroke Scale at 24 h, reperfusion at 24 h, symptomatic intracranial hemorrhage at 36 h, and mortality at 90 days. A network meta-analysis using a frequentist random-effects model was conducted to report relative risks and 95% confidence intervals. Interventions were ranked using the cumulative ranked area under the curve, and the certainty of the evidence was assessed using the GRADE/CINeMA framework.ResultsA total of 10 RCTs (2,409 patients) were included, involving five interventions: alteplase (rt-PA), tenaplase (TNK), JX10, standard of care (SoC), and placebo (PBO). For the primary outcome of 90-day mRS 0–2, compared with SoC, rt-PA significantly increased the proportion of functionally independent patients (RR = 1.21, 95% CI 1.06–1.38, low certainty), JX10 (RR = 1.50, 95% CI 0.87–2.58, very low certainty) and TNK (RR = 1.07, 95% CI 0.93–1.23, low certainty) showed a trend toward improvement but did not reach statistical significance. The SUCRA ranking showed that JX10 (87.7%) and rt-PA (77.0%) ranked first and second, respectively. Regarding the early surrogate endpoint of 24-h reperfusion, rt-PA (RR = 2.65, 95% CI 1.57–4.46, low certainty) was superior to SoC and ranked first in the SUCRA ranking (99.9%). Regarding safety, rt-PA significantly increased the risk of 36-h SICH compared with SoC (RR = 5.82, 95% CI 1.47–22.95, low certainty), while JX10 had the highest risk of bleeding (SUCRA 82.1%). There were no statistically significant differences in 90-day mortality rates among the interventions. The certainty of the evidence was predominantly low to very low, primarily limited by risk of bias, imprecision, and indirectness.ConclusionIn patients with acute IS within 4.5–24 h of onset, rt-PA significantly improves functional independence at 90 days and 24-h reperfusion, but increases the risk of symptomatic intracranial hemorrhage. The ranking analysis suggested JX10 might have a favorable functional outcome profile, but this finding is derived from a single, small-sample, dose-exploratory study n = 90 with no direct comparative data against other thrombolytics. Consequently, the evidence for JX10 is considered hypothesis-generating only, and its clinical efficacy and safety remain unestablished. Given the high risk of hemorrhage, its clinical application is not yet supported. The therapeutic advantages of TNK have not been fully demonstrated, though its safety profile is relatively superior. Clinical decision-making requires individualized consideration based on imaging screening, bleeding risk assessment, and patient preference. There is an urgent need for larger-scale, rigorously designed head-to-head RCTs to provide higher-quality evidence for expanding the time window for thrombolytic therapy.Systematic trial registrationhttps://www.crd.york.ac.uk/PROSPERO/view/CRD420261350208, identifier: CRD420261350208
