PROST-2
(2025)Objective
To assess the non-inferiority of intravenous recombinant human prourokinase compared with alteplase in patients with acute ischaemic stroke who were ineligible for or refused endovascular thrombectomy.
Study Summary
• Prourokinase showed lower rates of symptomatic intracranial haemorrhage (0.3% vs 1.3%, p=0.021)
• No difference in mortality between groups (0.6% vs 1.7% at 7 days)
Intervention
Intravenous recombinant human prourokinase (35 mg: 15 mg bolus + 20 mg infusion over 30 min) vs alteplase (0.9 mg/kg, max 90 mg)
Inclusion Criteria
Age >18 years, acute ischaemic stroke with NIHSS 4-25, treatment within 4.5 hours, pre-stroke mRS ≤1, ineligible for or refused endovascular thrombectomy
Study Design
Arms: Recombinant human prourokinase (n=775) vs Alteplase (n=777)
Patients per Arm: 775 vs 777
Outcome
• Safety: Lower symptomatic ICH with prourokinase (0.3% vs 1.3%)
• Similar rates of good functional outcome (mRS 0-2) and mortality
Bottom Line
Recombinant human prourokinase was non-inferior to alteplase for excellent functional outcome at 90 days with lower rates of symptomatic intracranial haemorrhage, supporting its use as an alternative thrombolytic agent.
Major Points
- Phase 3, open-label, non-inferiority randomised controlled trial conducted at 61 hospitals in China
- 1552 patients randomized 1:1 to receive prourokinase (35 mg) or alteplase (0.9 mg/kg) within 4.5 hours of stroke onset
- Primary outcome of mRS 0-1 at 90 days achieved by 72.0% with prourokinase vs 68.7% with alteplase (RR 1.04, 95% CI 0.98-1.10)
- Non-inferiority established with margin of 0.93 for risk ratio (p<0.0001)
- Significantly lower symptomatic intracranial haemorrhage with prourokinase (0.3% vs 1.3%, p=0.021)
- Lower rates of major bleeding (0.5% vs 2.1%) and clinically relevant non-major bleeding (26.1% vs 30.7%) with prourokinase
- No significant difference in mortality between groups
Study Design
- Study Type
- Phase 3, open-label, non-inferiority, randomised controlled trial
- Randomization
- Yes
- Blinding
- Open-label treatment administration but masked outcome assessment at 90 days by certified assessors; clinical event adjudication committee blinded to treatment assignment
- Sample Size
- 1552
- Follow-up
- 90 days
- Centers
- 61
- Countries
- China
Primary Outcome
Definition: Proportion of patients with modified Rankin Scale score of 0-1 at 90 days
| Control | Intervention | HR/OR | P-value |
|---|---|---|---|
| 534/777 (68.7%) | 558/775 (72.0%) | - (0.98 to 1.10) | <0.0001 for non-inferiority |
Limitations & Criticisms
- Open-label design could introduce bias despite blinded outcome assessment
- Conducted only in Chinese patients, limiting generalizability to other populations
- Women were under-represented in the study population
- Patients eligible for endovascular thrombectomy were excluded
- No advanced imaging used to identify large arterial occlusion status at baseline
- Requirement for written informed consent may have delayed door-to-needle times
- Data on stroke mimic rates not collected
- Reasons for endovascular thrombectomy ineligibility not systematically collected
Citation
The Lancet Neurology, Volume 24, Issue 1, January 2025, Pages 33-41