RAISE Trial: Reteplase vs Alteplase for Acute Ischemic Stroke
In patients with acute ischemic stroke within 4.5 hours eligible for standard thrombolysis, is IV reteplase (double-bolus 18 mg + 18 mg) superior to IV alteplase 0.9 mg/kg for excellent functional outcome (mRS 0-1) at 90 days?
Li S, et al. (NEJM 2024) · 1412 patients
Population
Included
- Acute ischemic stroke within 4.5 hours of onset
- Standard IV thrombolysis criteria met
- Age 18 or older
- Aged 18 to 80 years
- Able to receive intravenous thrombolysis within 4.5 hours after the time last known to be well
- Excellent functional status before the stroke, defined by a modified Rankin scale score of 1 or less
- Disabling ischemic stroke with a National Institutes of Health Stroke Scale score of 4 to 25
- Eligibility for thrombolysis based on Chinese guideline recommendations, consistent with US and European national guidelines
Excluded
- Contraindication to thrombolysis
- Hemorrhagic stroke on baseline imaging
- Severe hepatic impairment or known bleeding diathesis
- Previously undergone or planned to undergo endovascular thrombectomy
- Contraindication to intravenous thrombolysis per standard criteria
Source: Li S et al., NEJM 2024· Retrieved 2026-06-09
Primary Outcome
mRS 0-1 at 90 Days
Study Arms
- Agent
- Reteplase
- Dose
- 18 mg, then a second 18 mg dose
- Route
- IV
- Frequency
- Two bolus doses, each over 2 minutes; first immediately after randomization, second 30 minutes later
- Duration
- Two boluses 30 minutes apart
Reteplase is a recombinant plasminogen activator given as a fixed double-bolus regimen. It is approved for stroke only in selected regions and is not approved in the US or EU.
- Agent
- Alteplase
- Dose
- 0.9 mg/kg (max 90 mg)
- Route
- IV
- Frequency
- 10% delivered as a bolus within 1 minute, then remainder infused over 60 minutes
- Duration
- 60 minutes
Safety
Symptomatic intracranial hemorrhage within 36 hours
2.4%
2%
sICH was similar between arms (RR 1.21, 95% CI 0.54-2.75, P not significant). Any intracranial hemorrhage at 90 days was higher with reteplase (7.7% vs 4.9%, RR 1.59, 95% CI 1.00-2.51).
Any adverse events
91.6%
82.4%
Overall adverse events were higher with reteplase (91.6% vs 82.4%, RR 1.11, 95% CI 1.03-1.20). Any intracranial hemorrhage was 7.7% vs 4.9%.
Trial Design
Type
- Randomized controlled superiority trial
- Reteplase double bolus vs alteplase infusion
- Treatment within 4.5 hours
Timeline
China; NEJM 2024
N
1412
Enrollment
1,412 patients at multiple centres in China. Randomized superiority trial. Published NEJM 2024.
ClinicalTrials.gov
NCT05295173Bedside Pearl
RAISE is the first RCT showing a thrombolytic (reteplase) superior to alteplase for stroke (79.5% vs 70.4%, NNT 11, P=0.002). However, any-ICH was higher (7.7% vs 4.9%) and adverse events were higher (91.6%). Reteplase is not guideline-endorsed for stroke outside of select regions. Watch for replication trials and guideline updates.
See also