PROST Trial: Recombinant Human Prourokinase vs Alteplase
In patients with acute ischemic stroke within 4.5 hours, is intravenous recombinant human prourokinase (rhPro-UK) non-inferior to IV alteplase 0.9 mg/kg for excellent functional outcome (mRS 0-1) at 90 days?
PROST Investigators (JAMA Netw Open 2023) · 663 patients
Population
Included
- Acute ischemic stroke within 4.5 hours of onset
- Age 18 to 80 years
- Standard thrombolysis criteria met
- NIHSS assessed at baseline
- Aged 18 to 80 years
- Diagnosed with acute ischemic stroke (AIS)
- Stroke onset within 4.5 hours of symptom onset
- A stroke severity score of 4 to 25 on the National Institutes of Health Stroke Scale (NIHSS)
- Cerebral computed tomography (CT) performed before randomization to exclude patients with intracranial hemorrhage or massive ischemic infarction (defined as hypodensity greater than one-third of the middle cerebral artery territory on CT)
- Written informed consent obtained from the patient or a legal representative before enrollment
Excluded
- Hemorrhagic stroke or large established infarct on baseline imaging
- Contraindication to IV thrombolysis
- Severe hepatic or renal impairment
- Intracranial hemorrhage or massive ischemic infarction (hypodensity greater than one-third of the middle cerebral artery territory) on baseline CT
- Stroke or myocardial infarction within the previous 3 months
- A history of intracranial hemorrhage
- Planned endovascular treatment
- Other exclusion criteria mainly based on current contraindications to intravenous thrombolysis, determined a priori (full list in the trial protocol)
Source: Song H et al., JAMA Network Open 2023· Retrieved 2026-06-09
Primary Outcome
Negligible absolute difference
mRS 0-1 at 90 Days
Study Arms
- Agent
- Recombinant human prourokinase (rhPro-UK), a fibrin-specific plasminogen activator that acts mainly on fibrin at the thrombus site
- Dose
- 35 mg total
- Route
- Intravenous
- Frequency
- A 15 mg bolus over 3 minutes, then the remaining 20 mg by continuous infusion within 30 minutes
- Duration
- About 30 minutes
- Co-interventions
- rhPro-UK was the sole thrombolytic in this arm and was not combined with other thrombolytic drugs. Antiplatelet therapy was given when clinically necessary but not within 24 hours of the start of thrombolysis. Except for pulmonary embolism, lower-extremity atrial fibrillation, or deep venous thrombosis, anticoagulants were not used.
Dose and administration verbatim from Song JAMA Network Open 2023 p.3 (Randomization and Masking). Open-label, alteplase-controlled phase 3 noninferiority trial at 35 centers in China; mITT 663. NI margin was a between-group difference of less than 10 percentage points on mRS 0-1 at 90 days. ChiCTR1800016519; ClinicalTrials.gov NCT03541668.
- Agent
- Alteplase (recombinant tissue plasminogen activator)
- Dose
- 0.9 mg/kg (maximum 90 mg)
- Route
- Intravenous
- Frequency
- 10% administered as an intravenous bolus, followed by 90% infused within 1 hour
- Duration
- About 60 minutes
- Co-interventions
- Alteplase was the sole thrombolytic in this arm. Antiplatelet therapy was given when clinically necessary but not within 24 hours of the start of thrombolysis. Anticoagulants were not used except for pulmonary embolism, lower-extremity atrial fibrillation, or deep venous thrombosis.
Active comparator and current standard of care. Dose and administration verbatim from Song JAMA Network Open 2023 p.3 (Randomization and Masking).
Safety
Symptomatic intracranial hemorrhage at 90 days
1.5%
1.8%
sICH was similar and numerically lower with rhPro-UK (1.5% vs 1.8%, P>0.99). Systemic bleeding was significantly lower: 25.8% vs 42.2%.
Trial Design
Type
- Randomized, alteplase-controlled, open-label phase 3 trial
- rhPro-UK vs alteplase within 4.5 hours
- 35 centres in China
Timeline
China; May 2018 to May 2020
N
663
Enrollment
663 patients at 35 centres in China. Open-label, alteplase-controlled phase 3 RCT. May 2018 to May 2020. Published JAMA Netw Open 2023.
Bedside Pearl
PROST showed rhPro-UK was non-inferior to alteplase with dramatically lower systemic bleeding (25.8% vs 42.2%). For patients at high risk of systemic complications (active GI ulcer, recent surgery, coagulopathy), rhPro-UK may offer a meaningful safety advantage if approved in your setting. Confirmed and expanded in PROST-2.
See also