Thrombectomy plus intra-arterial alteplase increases excellent functional outcome to 57.5% at 90 daysAdding Alteplase to Thrombectomy Improves Stroke Recovery in This Trial

JAMA Published June 3, 2026 Study authors: Renú Arturo, Fernández-Couto María Dolores, de la Riva Patricia, Delgado-Mederos Raquel, Herrera Mar… PubMed ↗ NCT05797792 ↗ DOI ↗ Editorial oversight: Dr. Ji-eun Park, MD · Brain, Mind & Pain

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Key Takeaway

Consider that adjunctive intra-arterial alteplase with thrombectomy may improve functional outcomes but increases mortality, requiring careful risk-benefit assessment.

This was a randomized, open-label trial with blinded outcome assessment conducted at 14 stroke centers in Spain. The population included 440 patients with acute ischemic stroke due to large vessel occlusion who were treated with thrombectomy within 24 hours and achieved an expanded Treatment in Cerebral Ischemia score of 2b50 to 3. The intervention was thrombectomy plus intra-arterial alteplase at a dose of 0.225 mg/kg, with a maximum dose of 20 mg, infused over 15 minutes. The comparator was thrombectomy alone. The primary outcome was excellent functional outcome at 90 days, defined as a modified Rankin Scale score of 0 or 1.

The primary outcome results showed that 57.5% (123/214) of patients in the thrombectomy plus intra-arterial alteplase group achieved an excellent functional outcome, compared to 42.5% (93/219) in the thrombectomy alone group. The adjusted risk difference was 15.0% (95% CI, 5.7% to 24.3%; P = .002), indicating a statistically significant increase. Key secondary outcomes included residual hypoperfusion on follow-up computed tomography perfusion, which was lower in the combination group at 28.6% (55/192) versus 50.5% (96/190) in the thrombectomy alone group (adjusted risk difference, -22.0%; 95% CI, -31.5% to -12.4%; P < .001).

Symptomatic intracranial hemorrhage occurred in 1.4% (3/214) of the combination group versus 0.5% (1/219) of the thrombectomy alone group (adjusted odds ratio, 3.10; 95% CI, 0.32 to 30.0; P = .33), which was not statistically significant. Mortality at 90 days was higher in the combination group at 12.1% (26/214) versus 6.4% (14/219) in the thrombectomy alone group (adjusted risk difference, 5.9%; 95% CI, 0.5% to 11.3%; P = .03).

Safety findings focused on symptomatic intracranial hemorrhage as the primary adverse event and serious adverse event. The trial did not report data on discontinuations or overall tolerability. The higher mortality in the thrombectomy plus intra-arterial alteplase group was identified as a key limitation and warrants further study.

These results can be compared to prior landmark studies in acute ischemic stroke, such as the MR CLEAN and DAWN trials, which established the benefit of thrombectomy alone. This study adds evidence on the potential adjunctive role of intra-arterial alteplase, but the increased mortality raises questions about net clinical benefit.

Key methodological limitations include the open-label design, which could introduce performance bias, although outcome assessment was blinded. The study was conducted in a specific setting of 14 centers in Spain, which may limit generalizability to other regions or healthcare systems. Potential biases include selection bias in patient enrollment and the lack of reported funding or conflicts of interest.

Clinical implications suggest that while adjunctive intra-arterial alteplase may improve functional outcomes, the increased mortality requires careful consideration in practice decisions. Clinicians should weigh the benefits against the risks on an individual patient basis.

Unanswered questions include the optimal dosing and timing of intra-arterial alteplase, the mechanisms behind the increased mortality, and whether these findings replicate in larger, more diverse populations. Further research is needed to clarify the net clinical benefit and safety profile.

Stroke survivors often face a difficult road to recovery, with many left with lasting disabilities. This research offers new hope for patients with acute ischemic stroke caused by a large blockage in a major blood vessel. The study focuses on those who received a mechanical procedure called thrombectomy within 24 hours of symptom onset. These patients also had a specific score indicating a higher risk of poor outcomes if not treated aggressively. The goal was to see if adding a drug called alteplase directly into the artery could improve results without causing dangerous side effects.

Researchers conducted a randomized trial at 14 stroke centers in Spain. They compared two groups of patients. One group received thrombectomy alone. The other group received thrombectomy plus intra-arterial alteplase. The drug was given at a dose of 0.225 mg per kilogram, up to a maximum of 20 mg, infused over 15 minutes. The teams did not know which treatment each patient received when assessing the main results, though the doctors knew the treatment given. This design helps ensure the findings are reliable.

The main result measured excellent functional outcome at 90 days. This means the patient could perform daily tasks independently. In the group receiving the drug plus the procedure, 57.5 percent achieved this excellent outcome. In the group receiving the procedure alone, 42.5 percent achieved it. This represents a 15 percent increase in the chance of a great recovery. The difference was statistically significant, with a p-value of 0.002. The confidence interval ranged from 5.7 percent to 24.3 percent.

Safety was a major concern. The researchers looked for residual hypoperfusion, which means poor blood flow remaining in the brain. This was much less common in the group receiving the drug. They also checked for symptomatic intracranial hemorrhage, or bleeding inside the skull that causes symptoms. The rate was 1.4 percent in the drug group and 0.5 percent in the procedure-only group. This difference was not statistically significant, meaning the data does not prove the drug caused more bleeding. However, the study did find higher mortality in the drug group. Twelve point one percent died in the drug group versus 6.4 percent in the other group. This difference was statistically significant.

The study has important limitations that patients must understand. The higher death rate in the group receiving the drug warrants further study. Because of this, the evidence is not yet complete. The trial was small, with only 440 patients total. It was also open-label, meaning the treating doctors knew which treatment was given, which can influence care. The funding source was not reported. These factors mean the results should not be viewed as definitive proof that this approach is better for everyone.

For patients right now, this study suggests that adding intra-arterial alteplase might increase the chance of excellent recovery. It did not significantly increase the risk of bleeding in this specific group. However, the increased mortality rate is a serious concern that needs more investigation. Patients should discuss these trade-offs with their doctors. This single trial does not change standard practice immediately. More research is needed to confirm if the benefits outweigh the risks of higher death rates. Patients should not start or stop any medication based on this report alone.

What this means for you:

Adding alteplase to thrombectomy improved recovery but increased death rates; more study is needed.

Study Details

Study typeRct

Sample sizen = 440

EvidenceLevel 2

PublishedJun 2026

PMID42096239

TrialNCT05797792

View Original Abstract ↓

IMPORTANCE: Despite high recanalization rates with endovascular thrombectomy for acute ischemic stroke due to large vessel occlusion, functional outcomes remain suboptimal. The benefit of adjunctive intra-arterial thrombolysis after successful thrombectomy is uncertain. OBJECTIVE: To assess whether adjunctive intra-arterial alteplase after successful thrombectomy improves functional outcomes and cerebral reperfusion. DESIGN, SETTING, AND PARTICIPANTS: Randomized, open-label trial with blinded outcome assessment conducted at 14 stroke centers in Spain from December 11, 2023, through November 26, 2025. A total of 440 patients with acute ischemic stroke due to large vessel occlusion treated with thrombectomy within 24 hours and achieving an expanded Treatment in Cerebral Ischemia score of 2b50 to 3 were randomized. INTERVENTIONS: Thrombectomy plus intra-arterial alteplase (0.225 mg/kg; maximum dose, 20 mg) infused over 15 minutes (n = 221) or thrombectomy alone (n = 219). MAIN OUTCOMES AND MEASURES: The primary outcome was an excellent functional outcome at 90 days, which was defined as a modified Rankin Scale score of 0 or 1. There were 6 secondary outcomes, including residual hypoperfusion on follow-up computed tomography perfusion. The safety outcomes included symptomatic intracranial hemorrhage and death. RESULTS: Of 3786 patients treated with thrombectomy, 2776 (73%) fulfilled angiographic criteria and 440 (12%) were randomized. There were 433 patients who were treated as randomized (median age, 76 [IQR, 75-78] years; 51% female). At 90 days, 57.5% of patients (123/214) in the thrombectomy plus intra-arterial alteplase group had a modified Rankin Scale score of 0 or 1 vs 42.5% of patients (93/219) in the thrombectomy alone group (adjusted risk difference, 15.0% [95% CI, 5.7% to 24.3%]; P = .002). Of 6 secondary outcomes, 4 showed no significant between-group differences. Residual hypoperfusion occurred in 28.6% (55/192) of patients in the thrombectomy plus intra-arterial alteplase group vs 50.5% (96/190) of patients in the thrombectomy alone group (adjusted risk difference, -22.0% [95% CI, -31.5% to -12.4%]; P < .001) and symptomatic intracranial hemorrhage occurred in 1.4% (3/214) vs 0.5% (1/219), respectively (adjusted odds ratio, 3.10 [95% CI, 0.32 to 30.0]; P = .33). Mortality at 90 days was 12.1% (26/214) in the thrombectomy plus intra-arterial alteplase group vs 6.4% (14/219) in the thrombectomy alone group (adjusted risk difference, 5.9% [95% CI, 0.5% to 11.3%]; P = .03). CONCLUSIONS AND RELEVANCE: Among patients with acute ischemic stroke and successful thrombectomy, adjunctive intra-arterial alteplase increased the proportion achieving excellent functional outcome at 90 days without a significant increase in symptomatic intracranial hemorrhage. Higher mortality in the thrombectomy plus intra-arterial alteplase group warrants further study. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT05797792.

Thrombectomy plus intra-arterial alteplase increases excellent functional outcome to 57.5% at 90 daysAdding Alteplase to Thrombectomy Improves Stroke Recovery in This Trial

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Thrombectomy plus intra-arterial alteplase increases excellent functional outcome to 57.5% at 90 daysAdding Alteplase to Thrombectomy Improves Stroke Recovery in This Trial

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