Alteplase Treatment Within 24 Hours of Stroke Onset Improved Outcomes in HOPE Trial

Intravenous Activase treatment (alteplase; Genentech, South San Francisco, CA) administered between 4.5 and 24 hours after acute ischemic stroke onset improved functional outcomes in individuals with imaging-confirmed salvageable brain tissue who were not initially planned for thrombectomy. According to results of the phase 3 HOPE clinical trial (NCT04879615) published in JAMA, approximately 40% of participants treated with Activase achieved functional independence at 90 days compared with 26% of those receiving standard medical treatment, despite a higher rate of symptomatic intracranial hemorrhage associated with Activase treatment.

HOPE was a phase 3, open-label, blinded end-point study conducted across 26 stroke centers in China. The study included 372 participants presenting 4.5 to 24 hours after stroke onset, identified via CT perfusion as having salvageable brain tissue. Participants were randomized 1:1 into 2 groups of 186 participants each, 1 group receiving Activase treatment (0.9 mg/kg; maximum, 90 mg) and the other receiving standard therapy. Participants eligible for thrombectomy were excluded unless they declined the procedure. The primary end point was the percentage of participants who achieved nondisabled functional independence, defined as a modified Rankin Scale (mRS) score of 0 to 1 at 90 days.

The following key results were reported:

• In terms of the primary end point, functional independence was achieved in 40.3% (n=75) of those treated with Activase vs 26.3% (n=49) of those treated with standard therapy (adjusted risk ratio, 1.52 [95% CI, 1.14 to 2.02; P=.004]).
• There was a higher incidence of symptomatic intracranial hemorrhage for those treated with Activase (3.8%) vs standard treatment (0.51%) (adjusted risk ratio, 7.34 [95% CI, 1.54 to 34.84; P=.01]).
• Mortality was 10.8% in both groups (adjusted risk ratio, 0.91 [95% CI, 0.52 to 1.62; P=.76]).

Results of the phase 3 EXPECTS clinical trial (NCT0549476) published earlier this year also demonstrated a significant improvement in functional outcomes in people treated with Activase 4.5 to 24 hours after stroke vs standard treatment. The EXPECTS study evaluated Activase treatment in people with posterior circulation ischemic stroke and no planned thrombectomy.

Source: Zhou Y, He Y, Campbell BCV, et al. Alteplase for Acute Ischemic Stroke at 4.5 to 24 Hours: The HOPE Randomized Clinical Trial. JAMA. Published online August 07, 2025. doi:10.1001/jama.2025.12063.