Phase III EXPECTS Trial Finds Alteplase Boosts 90-Day Recovery in Posterior Circulation Stroke Patients

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Findings from the Phase III EXPECTS clinical trial (NCT05429476) show that in patients experiencing a mostly mild posterior circulation stroke who are not candidates for thrombectomy, treatment with alteplase administered 4.5 to 24 hours following stroke onset produced a higher rate of functional independence at 90 days compared to standard care. The results of the trial, conducted in China and published by The New England Journal of Medicine, also show that these patients did not have an increased risk of symptomatic intracranial hemorrhage.^1,2

“In this trial involving Chinese patients with posterior circulation stroke without extensive infarction, with or without large-vessel occlusion, alteplase administered between 4.5 and 24 hours after the onset of stroke was associated with a higher incidence of functional independence at 90 days than standard medical treatment,” the study authors wrote. “The incidence of intracranial hemorrhage was similar in the two trial groups. These results support the use of alteplase in this extended time window if endovascular thrombectomy is not available.”

Alteplase is a tissue plasminogen activator indicated for the treatment of acute myocardial infarction to lower mortality and incidence of heart failure, pulmonary embolism associated with low blood pressure, and blocked central venous catheter, as well as for acute ischemic stroke.³

The study authors noted that standard care for an ischemic stroke involves administration of intravenous thrombolysis (IVT) within 4.5 hours after onset among eligible patients. Although endovascular thrombectomy is also part of a standard care regimen, IVT is typically used for cases in which endovascular thrombectomy is unavailable.

“Alteplase administered up to 9 hours after the onset of stroke has been shown to be effective in patients with salvageable brain tissue identified with the use of computed tomography (CT) perfusion or perfusion–diffusion magnetic resonance imaging (MRI),” the study authors wrote. “Two recent randomized controlled trials have explored the possibility of extending the treatment window for IVT to 24 hours after onset in patients with large-vessel occlusion of the anterior circulation identified with the use of perfusion imaging techniques.”¹

Trial Design

Investigators enrolled 234 patients with posterior circulation stroke, without extensive early hypodensity on computed tomography, and with no planned thrombectomy. Patients were randomly assigned in a 1:1 ratio to receive either alteplase at a dose of 0.9 mg per kilogram of body weight with a maximum dose of 90 mg (n = 117) or standard medical treatment (n = 117) 4.5 to 24 hours after the onset of symptoms.

The trial’s primary endpoint was functional independence on the modified Rankin scale at 90 days. The trial’s key safety endpoint was symptomatic intracranial hemorrhage and death.

Results show that 89.6% of patients administered alteplase achieved functional independence at 90 days compared to 72.6% in the standard treatment cohort (adjusted risk ratio, 1.16; 95% confidence interval [CI], 1.03 to 1.30; P=0.01).

Incidence of symptomatic intracranial hemorrhage within 36 hours was 1.7% among patients administered alteplase compared to 0.9% among patients administered standard treatment. At 90 days, 5.2% of patients administered alteplase died compared to 8.5% of those administered standard treatment.

“This trial explored late-window thrombolysis without the use of perfusion imaging for patient selection, leveraging the lower hemorrhagic risk in posterior circulation strokes to broaden the therapeutic window,” the study authors wrote. “Our criteria for diagnosing posterior circulation stroke confirmed the feasibility of identifying and treating these cases in emergency settings and provide a basis for future trials focusing on posterior circulation.”

References

1. Yan S., et al. Alteplase for Posterior Circulation Ischemic Stroke at 4.5 to 24 Hours. N Engl J Med 2025;392:1288-1296. DOI: 10.1056/NEJMoa2413344. VOL. 392 NO. 13.

2. EXtending the Time Window for Thrombolysis in Posterior Circulation Stroke Without Early CT Signs. ClinicalTrials.gov. Updated December 18, 2024. Accessed April 8, 2025. https://clinicaltrials.gov/study/NCT05429476

3. Label for ACTIVASE [Supplement 5203, Action Date 02/13/2015]. fda.gov. Accessed April 8, 2025.