PROST-2 Trial: Large Phase 3 Prourokinase vs Alteplase Trial
In patients with acute ischemic stroke within 4.5 hours who are ineligible for or refusing endovascular thrombectomy, is prourokinase non-inferior to IV alteplase 0.9 mg/kg for excellent functional outcome (mRS 0-1) at 90 days?
PROST-2 Investigators (Lancet Neurol 2024) · 1552 patients
Population
Included
- Acute ischemic stroke within 4.5 hours of onset
- Ineligible for or refusing endovascular thrombectomy
- Standard thrombolysis criteria met
- Age 18 or older
Core inclusion
- Age older than 18 years
- Acute ischaemic stroke with a baseline NIHSS score of 4 to 25
- Able to undergo randomisation within 4.5 h of stroke onset
- Pre-stroke modified Rankin Scale score of no more than 1 (known to be well before the stroke)
- Diagnosis of ischaemic stroke based on neurological impairment persisting for a minimum of 30 min with no significant improvement, typically with non-contrast CT or MRI
- Met additional eligibility requirements for intravenous thrombolysis under Chinese guideline recommendations
Endovascular thrombectomy status
- Deemed ineligible for endovascular thrombectomy, OR refused endovascular thrombectomy
Excluded
- Eligible for and agreeing to endovascular thrombectomy
- Hemorrhagic stroke or large infarct core on baseline imaging
- Contraindication to IV thrombolysis
Endovascular and protocol exclusions
- Eligible for and agreeing to undergo endovascular thrombectomy (patients who had thrombectomy were excluded, consistent with the TRACE-2 and TRACE-3 trials, to avoid affecting the proportion of patients reaching the primary efficacy outcome)
- Failure to meet standard intravenous thrombolysis criteria
Source: Li et al., Lancet Neurol 2025;24:33-41· Retrieved 2026-06-09
Primary Outcome
Small absolute difference — interpret with caution
mRS 0-1 at 90 Days
Study Arms
- Agent
- Recombinant human prourokinase
- Dose
- 35 mg total (15 mg bolus followed by 20 mg infusion)
- Route
- Intravenous
- Frequency
- Single treatment course
- Duration
- 15 mg bolus, then 20 mg infused over 30 min
- Co-interventions
- Standard acute ischaemic stroke care and secondary prevention per Chinese guideline recommendations
Glycosylated single-chain proenzyme, fibrin-specific. Administered open-label.
- Agent
- Alteplase
- Dose
- 0.9 mg/kg, maximum 90 mg
- Route
- Intravenous
- Frequency
- Single treatment course
- Duration
- 10% bolus within 1 min, remainder infused over 60 min
- Co-interventions
- Standard acute ischaemic stroke care and secondary prevention per Chinese guideline recommendations
Standard-of-care intravenous thrombolytic comparator. Noninferiority margin for the risk ratio was 0.93.
Safety
Symptomatic intracranial hemorrhage
0.3%
1.3%
sICH was significantly lower with prourokinase (0.3% vs 1.3%), a key safety advantage alongside lower major bleeding (0.5% vs 2.1%).
Major bleeding at 7 days
0.5%
2.1%
Major bleeding was significantly lower with prourokinase (0.5% vs 2.1%), consistent with its fibrin-specific mechanism limiting systemic plasminogen activation.
Trial Design
Type
- Phase 3, open-label, noninferiority randomized trial
- Patients ineligible for or refusing EVT
- Prourokinase vs alteplase within 4.5 hours
Timeline
China; January 2023 to March 2024
N
1552
Enrollment
1,552 patients at multiple Chinese centres. Phase 3 open-label NI RCT. January 2023 to March 2024. Published Lancet Neurol 2024.
ClinicalTrials.gov
NCT05700591Bedside Pearl
PROST-2 confirmed prourokinase as non-inferior to alteplase with better safety: sICH 0.3% vs 1.3% and major bleeding 0.5% vs 2.1%. It is currently available only in China. For clinicians in systems where prourokinase is approved, PROST-2 supports it as a first-line IVT alternative. Particularly when minimizing bleeding is a priority.
See also