HOPE
(2025)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 on perfusion imaging, regardless of large vessel occlusion status, who were not initially planned for thrombectomy.
Study Summary
• Unadjusted absolute risk difference: 13.98% (95% CI 4.50%-23.45%)
• Symptomatic intracranial hemorrhage: 3.8% vs 0.51%, adjusted RR 7.34 (95% CI 1.54-34.84), P=.01
• 90-day all-cause mortality: 11% in both groups (adjusted RR 0.91, 95% CI 0.52-1.62, P=.76)
Intervention
Intravenous alteplase 0.9 mg/kg (maximum 90 mg; 10% bolus over 1 minute, remainder over 60-minute infusion) vs standard medical treatment, administered 4.5 to 24 hours after stroke onset in patients with salvageable tissue on CT perfusion.
Inclusion Criteria
Age ≥18 years; acute ischemic stroke with onset (or midpoint of last known well and symptom recognition) 4.5-24 hours prior; NIHSS 4-26; prestroke mRS 0-1; salvageable tissue on CT perfusion (ischemic core ≤70 mL, mismatch ratio ≥1.2, mismatch volume ≥10 mL); no initial plan for endovascular thrombectomy.
Study Design
Arms: IV Alteplase 0.9 mg/kg (n=186) vs Standard medical treatment (n=186)
Patients per Arm: 186 per arm
Outcome
• Symptomatic ICH within 36 hours: 3.8% vs 0.51% (adjusted RR 7.34, 95% CI 1.54-34.84, P=.01)
• 90-day mortality: 11% in both groups (no significant difference)
Bottom Line
In patients with acute ischemic stroke and salvageable brain tissue on CT perfusion presenting 4.5-24 hours after onset who were not initially planned for thrombectomy, intravenous alteplase increased functional independence at 90 days (40% vs 26%, adjusted RR 1.52) at the cost of a higher rate of symptomatic intracranial hemorrhage (3.8% vs 0.51%), with no difference in mortality.
Major Points
- Intravenous alteplase given 4.5-24 hours after stroke onset improved 90-day functional independence (mRS 0-1) from 26% to 40% (adjusted RR 1.52, 95% CI 1.14-2.02, P=.004).
- Unadjusted absolute risk difference for the primary outcome was 13.98% (95% CI 4.50%-23.45%).
- Symptomatic intracranial hemorrhage was significantly higher with alteplase (3.8% vs 0.51%; adjusted RR 7.34, 95% CI 1.54-34.84, P=.01; absolute risk difference 3.23%).
- 90-day all-cause mortality was 11% in both groups (adjusted RR 0.91, 95% CI 0.52-1.62, P=.76).
- Eligibility did not require large vessel occlusion — patients with distal occlusions or no occlusion could be enrolled if perfusion mismatch was present.
- Patients with planned thrombectomy were excluded; the trial population represents those who declined or were not candidates for endovascular therapy.
- Trial conducted at 26 centers in China; findings support extending IV thrombolysis to the 4.5-24 hour window with perfusion imaging selection, especially valuable in settings where thrombectomy is unavailable.
Study Design
- Study Type
- Randomized, open-label, blinded end-point (PROBE) trial
- Randomization
- Yes
- Blinding
- Open-label treatment; outcome assessors and adjudication committee blinded to treatment assignment
- Sample Size
- 372
- Follow-up
- 90 days
- Centers
- 26
- Countries
- China
Primary Outcome
Definition: Functional independence defined as modified Rankin Scale (mRS) score of 0 to 1
| Control | Intervention | HR/OR | P-value |
|---|---|---|---|
| 49/186 (26%) | 75/186 (40%) | - (1.14-2.02) | 0.004 |
Limitations & Criticisms
- Open-label design (though outcome assessment was blinded) — potential for performance bias
- Conducted entirely in China at 26 centers — generalizability to other populations and healthcare systems requires confirmation
- Patients eligible for thrombectomy who accepted the procedure were excluded — results do not apply to thrombectomy candidates
- Significant increase in symptomatic ICH (over 7-fold relative risk) must be weighed against functional benefit
- Sample size calculation based on a small (n=62) observational cohort from the coordinating center
Citation
JAMA. 2025;334(9):788-797. doi:10.1001/jama.2025.12063