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Clinical Trial
. 2025 Sep 2;334(9):788-797.
doi: 10.1001/jama.2025.12063.

Alteplase for Acute Ischemic Stroke at 4.5 to 24 Hours: The HOPE Randomized Clinical Trial

Ying Zhou  1   2 , Yaode He  1   2 , Bruce C V Campbell  3 , David S Liebeskind  4 , Changzheng Yuan  5   6 , Hui Chen  5 , Yanxing Zhang  7 , Tingyu Yi  8 , Zhongyu Luo  1 , Zuowen Zhang  9 , Changcai Meng  10 , Jianhua Cheng  11 , Hezhong Ouyang  12 , Jin Hu  13 , Fei Wang  14 , Sheng Zhang  15 , Qi Fang  16 , Haitao Hu  1   2 , Xuting Zhang  1   2 , Yi Chen  1   2 , Wansi Zhong  1   2 , Maarten G Lansberg  17 , Shenqiang Yan  1   2 , Min Lou  1   2 ; HOPE investigators
Collaborators, Affiliations
Clinical Trial

Alteplase for Acute Ischemic Stroke at 4.5 to 24 Hours: The HOPE Randomized Clinical Trial

Ying Zhou et al. JAMA. .

Abstract

Importance: The safety and efficacy of intravenous thrombolytics beyond 4.5 hours after ischemic stroke onset remain inadequately studied.

Objective: To evaluate the safety and efficacy of intravenous alteplase administered 4.5 to 24 hours after stroke onset in patients with salvageable brain tissue, regardless of the presence of large vessel occlusion.

Design, setting, and participants: This randomized, open-label, blinded end-point trial was conducted at 26 stroke centers across China. A total of 372 patients with acute ischemic stroke and salvageable brain tissue identified by perfusion imaging were enrolled between June 21, 2021, and June 30, 2024 (final follow-up October 2, 2024). Eligibility criteria included stroke onset (or the midpoint between last known well and symptom recognition if onset was unknown) of 4.5 to 24 hours prior to presentation, and no initial plan for endovascular thrombectomy. Data were analyzed from December 2024 to February 2025.

Interventions: Patients were randomly assigned (1:1) using a minimization algorithm to receive intravenous alteplase (0.9 mg/kg; maximum dose, 90 mg; n = 186) or standard medical treatment (n = 186).

Main outcomes and measures: The primary efficacy outcome was functional independence, defined as a modified Rankin Scale score of 0 to 1 at 90 days. Safety outcomes included symptomatic intracranial hemorrhage within 36 hours and all-cause mortality within 90 days.

Results: Among 372 patients who were enrolled (median [IQR] age, 72 [64-80] years; 160 [43%] women), all completed the trial. The primary outcome occurred in 75 of 186 patients (40%) in the alteplase group and 49 of 186 (26%) in the control group (adjusted risk ratio, 1.52 [95% CI, 1.14-2.02]; P = .004; unadjusted risk difference, 13.98% [95% CI, 4.50%-23.45%]). The incidence of symptomatic intracranial hemorrhage was higher with alteplase at 3.8% compared with 0.51% with standard treatment (adjusted risk ratio, 7.34 [95% CI, 1.54-34.84]; P = .01; unadjusted risk difference, 3.23% [0.28%-6.19%]), and mortality was 11% in both groups (adjusted risk ratio, 0.91 [95% CI, 0.52-1.62]; P = .76; unadjusted risk difference, 0% [95% CI, -6.30% to 6.30%]).

Conclusions and relevance: In patients with acute ischemic stroke with salvageable brain tissue identified by perfusion imaging who did not initially receive thrombectomy, intravenous alteplase administered 4.5 to 24 hours after onset provided functional benefit, despite an increase in symptomatic intracranial hemorrhage.

Trial registration: ClinicalTrials.gov Identifier: NCT04879615.

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Conflict of interest statement

Conflict of Interest Disclosures: Dr Liebeskind reported support from Cerenovus, Genentech, Medtronic, Stryker, and Rapid Medical for the imaging core lab outside the submitted work. Dr Lansberg reported grants from National Institutes of Health/National Institute of Neurological Disorders and Stroke during the conduct of the study; personal fees from Genentech/Roche outside the submitted work. Dr Lou reported grants from National Natural Science Foundation of China and grants from the Second Affiliated Hospital of Zhejiang University, School of Medicine during the conduct of the study. No other disclosures were reported.

References

    1. Powers WJ, Rabinstein AA, Ackerson T, et al. Guidelines for the early management of patients with acute ischemic stroke: 2019 update to the 2018 guidelines for the early management of acute ischemic stroke: a guideline for healthcare professionals from the American Heart Association/American Stroke Association. Stroke. 2019;50(12):e344-e418. doi: 10.1161/STR.0000000000000211 - DOI - PubMed
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