Dose-specific Effects of Recombinant Human Prourokinase versus Alteplase in Acute Ischemic Stroke: A Network Meta-analysis
Medhansh Biradar1, Arkansh Sharma2, Rishu Raj3, Vinay Suresh4, Pavan Raju Kola5, Allimuthu Nithyanandam6, Muaz Ali7
1All India Institute of Medical Sciences, Raipur, 2Government Medical College, Omandurar, Chennai, Tamil Nadu, India, 3Atal Bihari Vajpayee Institute of Medical Sciences and Dr. RML Hospital, New Delhi, India, 4University of Oxford, United Kingdom, 5All India Institute Of Medical Sciences, New Delhi, India, 6Neurology, Department of Neurology, Tamil Nadu Government Multi-Super Speciality Hospital, Omandurar Government Estate, Chennai, India, 7Cleveland Clinical Florida, USA
Objective:
To evaluate the efficacy and safety of recombinant human prourokinase (rhPro-UK) at different dosing regimens compared with standard-dose alteplase in acute ischemic stroke using network meta-analysis.
Background:
Alteplase is the standard for intravenous thrombolysis in acute ischemic stroke, but rhPro-UK has emerged as a potential alternative. Prior analyses pooled rhPro-UK regimens despite dosing variation. Dose-specific evaluation may clarify relative benefits and risks.
Design/Methods:
We systematically searched PubMed, EMBASE, SCOPUS, and Web of Science up to September 2025 for randomized controlled trials (RCTs). A frequentist network meta-analysis was performed using the netmeta package in R with a random-effects model and DerSimonian–Laird estimator for τ². RCTs comparing rhPro-UK at different doses with alteplase 0.9 mg/kg were included. Outcomes were excellent and good functional outcomes, early neurological improvement, mortality, intracranial hemorrhage, and overall adverse events. Language refinement was assisted by ChatGPT (OpenAI, GPT-5).
Results:
Three RCTs involving 2,289 patients (1,141 rhPro-UK; 1,148 alteplase) were included. The 15 mg bolus plus 20 mg infusion of rhPro-UK showed no statistically significant difference compared with alteplase for excellent functional outcome (OR 1.13, 95% CI 0.94–1.35) or early neurological improvement (OR 1.05, 95% CI 0.82–1.35). Safety outcomes suggested a nonsignificant trend toward lower intracranial hemorrhage (OR 0.82, 95% CI 0.59–1.15) and overall adverse events (OR 0.94, 95% CI 0.74–1.20). Higher doses (35 mg and 50 mg) did not improve efficacy and showed more variability in safety estimates, with wide confidence intervals for mortality and adverse events. Heterogeneity across studies was low to moderate.
Conclusions:
The 15 mg bolus plus 20 mg infusion regimen of rhPro-UK appears to provide similar efficacy to standard-dose alteplase, with a possible trend toward improved safety. Higher doses did not demonstrate additional benefit. These findings suggest that rhPro-UK, at the 15+20 mg regimen, may be a reasonable alternative to alteplase, but evidence does not show clear superiority.
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