Pro-UK (recombinant human pro-urokinase for injection) / Tasly - LARVOL DELTA

Prourokinase for acute ischemic stroke: A meta-analysis of randomized controlled trials. (PubMed, Medicine (Baltimore)) - "While Pro-UK offers a theoretical advantage in reducing systemic bleeding due to its clot-specific action, current evidence does not significantly improve key clinical outcomes. The limited number and heterogeneity of existing randomized controlled trials underscore the need for more robust, large-scale trials to confirm its safety and efficacy in acute ischemic stroke."

Clinical • Journal • Retrospective data • Review • Cardiovascular • Cerebral Hemorrhage • CNS Disorders • Hematological Disorders • Ischemic stroke

Safety Outcomes Following Intravenous Thrombolysis in Acute Ischemic Stroke: A Systematic Review and Network Meta-analysis. (PubMed, CNS Drugs) - "Alteplase 0.6 mg/kg, rhPro-UK 35 mg, and nSta 10 mg were safer IVT options. Tenecteplase 0.25 mg/kg and alteplase 0.6 mg/kg were preferable beyond 4.5 h with tissue window assessment."

Journal • Retrospective data • Review • Cardiovascular • Cerebral Hemorrhage • CNS Disorders • Hematological Disorders • Ischemic stroke

Intravenous recombinant human prourokinase for acute ischemic stroke: a network meta-analysis. (PubMed, Minerva Med) - "Both 35 mg and 50 mg rhPro-UK improve early neurological outcomes. However, 40 mg rhPro-UK + ALT may offer the most favorable efficacy-safety profile. Further trials are warranted to optimize dosing strategies."

Journal • Retrospective data • Cardiovascular • Cerebral Hemorrhage • CNS Disorders • Hematological Disorders • Ischemic stroke

Study on the Effect of Intracoronary Thrombolysis with Recombinant Human Pro-urokinase (rhPro-UK) on TIMI Flow and Prognosis in STEMI Patients (PUK-ICT) (ChiCTR) - P=N/A | N=2585 | Not yet recruiting | Sponsor: The First Hospital of Lanzhou University; The First Hospital of Lanzhou University

New trial • Cardiovascular • Myocardial Infarction

Efficacy and safety of 35 mg of recombinant human prourokinase for thrombolysis in acute ischemic stroke: a meta-analysis of randomized controlled trials. (PubMed, Int J Clin Pharm) - "This meta-analysis suggested that 35 mg of rhPro-UK does not significantly differ from 50 mg of rhPro-UK or alteplase in terms of clinical outcomes among AIS patients. However, the 35-mg dose of rhPro-UK has the potential advantages of enhancing early neurological recovery and reducing the risk of systemic bleeding. Subgroup analysis revealed that 35 mg of rhPro-UK might be associated with a lower risk of SAEs than 50 mg of rhPro-UK."

Journal • Retrospective data • Review • Cardiovascular • Ischemic stroke

Comparative efficacy and safety of prourokinase versus alteplase for acute ischemic stroke within 4.5 hours: a systematic review and meta-analysis of randomized controlled trials. (PubMed, Neurol Res) - "However, concerns about cost and safety have led to an interest in alternative thrombolytics like prourokinase (rhPro-UK). Its advantages, including lower cost and ease of administration, make it a viable alternative. Future large-scale trials are recommended."

Journal • Retrospective data • Cardiovascular • Cerebral Hemorrhage • CNS Disorders • Hematological Disorders • Ischemic stroke

Recombinant Human Pro-Urokinase vs. Alteplase Within 4.5 hours of Acute Ischemic Stroke: A Systematic Review and Meta-Analysis of Randomized Controlled Trials. (PubMed, J Stroke Cerebrovasc Dis) - "This meta-analysis found no statistically significant differences between rhPro-UK and alteplase in terms of functional outcomes, early neurological improvement, or safety profiles in patients with acute ischemic stroke. rhPro-UK shows promise as a cost-effective alternative, but further large-scale RCTs are required to confirm its role in AIS management."

Journal • Retrospective data • Cardiovascular • Cerebral Hemorrhage • CNS Disorders • Hematological Disorders • Ischemic stroke

IS RECOMBINANT HUMAN PROUROKINASE SUPERIOR TO ALTEPLASE IN THE TREATMENT OF ACUTE ISCHEMIC STROKE WITHIN 4.5 HOURS AFTER STROKE ONSET? A SYSTEMATIC REVIEW AND META-ANALYSIS (ESOC 2025) - "This study aimed to compare recombinant human prourokinase (rhPro-UK) and alteplase for AIS treatment. Prourokinase demonstrated no superiority over alteplase, with the exception of a slight advantage in early NIHSS score improvement, and exhibited an acceptable and comparable safety profile."

Retrospective data • Review • Cardiovascular • Ischemic stroke

EFFICACY AND SAFETY OF INTRAVENOUS RECOMBINANT HUMAN PROUROKINASE VS RECOMBINANT TISSUE PLASMINOGEN ACTIVATOR IN THE TREATMENT OF ACUTE ISCHEMIC STROKE WITHIN 4.5 HOURS OF STROKE ONSET: A META-ANALYSIS OF RANDOMIZED CONTROLLED TRIALS (ESOC 2025) - "Intravenous rtPro-Uk appears to be a non-inferior alternative to alteplase for AIS within 4.5 hours, offering comparable efficacy with reduced risk of systemic bleeding."

Retrospective data • Cardiovascular • Ischemic stroke

Efficacy and Safety of Recombinant Human Prourokinase in Acute Ischemic Stroke: A Systematic Review and Meta-Analysis of Randomized Controlled Trials. (PubMed, Brain Sci) - " IV rhPro-UK provides non-inferior efficacy to both alteplase and standard care with a better safety profile at 35 mg, while IA rhPro-UK enhances functional outcomes in middle cerebral artery occlusions, albeit with safety concerns. Further trials are needed to confirm long-term outcomes, optimal dosing, and broader applicability."

Journal • Retrospective data • Review • Cardiovascular • Hematological Disorders • Ischemic stroke

Exploring the efficacy of recombinant human pro-urokinase in catheter-directed thrombolysis for acute lower extremity deep venous thrombosis patients. (PubMed, BMC Cardiovasc Disord) - "CDT with rhPro-UK significantly improves venous patency, reduces limb swelling, optimizes coagulation function, and minimizes complications compared to UK. Its fibrin-targeted mechanism enhances clinical efficacy and safety, supporting its adoption as a superior thrombolytic for acute DVT."

Journal • Cardiovascular • Hematological Disorders • Thrombosis

Head-to-Head: Recombinant Human Prourokinase Versus Intravenous Thrombolytics in Acute Ischemic Stroke Within 4.5 Hours - A Systematic Review and Network Meta-Analysis of Randomized Clinical Trials. (PubMed, Clin Appl Thromb Hemost) - "Emerging alternatives like recombinant human prourokinase (rhPro-UK), reteplase, and tenecteplase offer potential improvements in efficacy, safety, and convenience, necessitating a comparative analysis.MethodsElectronic databases, including PubMed, ScienceDirect, and Cochrane Central, were comprehensively searched from inception till December 2024 for relevant studies. Safety outcomes, symptomatic intracranial hemorrhage (sICH), and mortality were not significantly different between alteplase and other thrombolytics. According to P-scores, Reteplase 18 + 18 mg ranked the best for excellent functional outcome (P-score = 0.89) and TNK 0.32 mg for good functional outcome (P-score = 0.99), while rhPro-UK 35 mg ranked the best for sICH (P-score = 0.89).ConclusionReteplase 18 + 18 mg and TNK 0.32 mg demonstrated superior functional outcomes compared to alteplase, while rhPro-UK 35 mg showed the best safety profile with the lowest sICH risk."

Clinical • Head-to-Head • Journal • Retrospective data • Review • Cardiovascular • Cerebral Hemorrhage • CNS Disorders • Hematological Disorders • Ischemic stroke

Safety and efficacy of 35mg of intravenous recombinant human prourokinase for acute ischemic stroke: a systematic review and meta-analysis. (PubMed, Neurol Res) - "No significant differences were observed in intracranial hemorrhage (OR = 0.819 [0.598-1.140], p = 0.236), SAEs (OR = 0.907 [0.713-1.153], p = 0.426), or mortality (OR = 1.168 [0.790-1.726], p = 0.437). RhPro-UK improves short-term neurological outcomes without increasing hemorrhagic risk, SAEs, or mortality."

Journal • Retrospective data • Review • Cardiovascular • Cerebral Hemorrhage • CNS Disorders • Hematological Disorders • Ischemic stroke

Efficacy and Safety of Recombinant Human Prourokinase in Acute Ischemic Stroke: A Systematic Review and Meta-Analysis. (PubMed, Clin Appl Thromb Hemost) - "rhPro-UK demonstrates comparable efficacy to r-tPA with reduced NIHSS scores and systemic bleeding, supporting its role as a cost-effective and safer alternative for AIS treatment within 4.5 h. Further investigation in stroke management protocols is warranted."

Clinical • Journal • Retrospective data • Review • Cardiovascular • Cerebral Hemorrhage • Hematological Disorders • Ischemic stroke

Efficacy and Safety of Recombinant Human Prourokinase in Acute Ischemic Stroke Within 4.5 h: A Systematic Review and Meta-Analysis of Randomized Controlled Trials. (PubMed, Brain Behav) - "rhPro-UK demonstrated comparable efficacy to alteplase in achieving functional outcomes in AIS within 4.5 h, with no significant differences in mortality or neurological improvement. Although not statistically significant, a trend toward lower sICH risk with rhPro-UK highlights its potential safety advantage. More high-quality randomized clinical trials are required to confirm these findings."

Clinical • Journal • Retrospective data • Review • Cardiovascular • Cerebral Hemorrhage • CNS Disorders • Hematological Disorders • Ischemic stroke

Mechanism and prospects of rhPro-UK in acute pulmonary embolism. (PubMed, Asian J Surg) - No abstract available

Journal • Cardiovascular • Pulmonary Embolism • Respiratory Diseases

FIBRINOLYSIS WAS REPLACED BEFORE IT WAS UNDERSTOOD. (PubMed, Cardiology) - "Methods This uses a sequential combination of a 5 mg mini bolus of tPA followed by an infusion of proUK (40 mg/hr) for 90 minutes...This requires doses of 90-100 mg of tPA over 60 minutes, which is neither very effective nor safe, due to a risk of bleeding complications from the lysis of hemostatic fibrin by tPA's fibrin affinity. Due to this problem, fibrinolysis was replaced by interventional procedures, like percutaneous coronary intervention (PCI), which is much slower, limited to clots larger than the catheter, but is generously reimbursed by third party payers."

Journal

rhPro-UK in Acute Ischaemic Stroke Within 4.5 Hours of Stroke Onset Trial 2(PROST-2) (clinicaltrials.gov) - P3 | N=1552 | Completed | Sponsor: Tasly Biopharmaceuticals Co., Ltd. | Active, not recruiting ➔ Completed | Trial completion date: Dec 2024 ➔ Mar 2024

Trial completion • Trial completion date • Cardiovascular • Ischemic stroke

ProUrokinase in Mild IsChemic strokE (PUMICE) (clinicaltrials.gov) - P3 | N=1446 | Completed | Sponsor: Beijing Tiantan Hospital | Recruiting ➔ Completed

Trial completion • Cardiovascular • Hematological Disorders • Ischemic stroke • Thrombosis

Evaluation of Recombinant Human Prourokinase in the Treatment of Acute Pulmonary Embolism (ERUPTE): A Randomized, Single-Blinded, Multicenter, Phase 2 Trial (ISTH 2024) - P2a | "Baseline characteristics were comparable among three groups (Table 1). All patients achieved a reduction in mean sPAP at 24 hours: rhPro-UK 40 mg group, -13.40 mmHg (95% confidence interval [CI], -24.10 to -2.71); rhPro-UK 50 mg, -15.42 mmHg (95% CI -25.93, -4.91); and alteplase, -16.02 mmHg (95% CI -25.53, -6.51) (Figure 1), but without inter-group differences (P > 0.05). Incidence of bleeding was lower in two rhPro-UK groups (63.9%, 23/37 at 40 mg; 55.6%, 20/35 at 50 mg) compared to alteplase group (82.9%, 29/35) (P=0.04)."

Clinical • Late-breaking abstract • P2 data • Cardiovascular • Pulmonary Embolism • Respiratory Diseases

RhPro-UK in acute ischemic stroke within 4.5 hours of stroke onset trial-2(The PROST-2 study): Rationale and design of a multicenter, prospective, randomized, open-label, blinded-endpoint, controlled phase 3 non-inferiority trial. (PubMed, Int J Stroke) - P3 | "URL: http://www.clinicaltrials.gov. Unique identifier: NCT05700591."

Head-to-Head • Journal • P3 data • Cardiovascular • Cerebral Hemorrhage • CNS Disorders • Hematological Disorders • Ischemic stroke • Myocardial Infarction

rhPro-UK in Acute Ischaemic Stroke Within 4.5 Hours of Stroke Onset Trial 2(PROST-2) (clinicaltrials.gov) - P3 | N=1552 | Active, not recruiting | Sponsor: Tasly Biopharmaceuticals Co., Ltd. | Recruiting ➔ Active, not recruiting | Trial completion date: Jul 2024 ➔ Dec 2024

Enrollment closed • Trial completion date • Cardiovascular • Ischemic stroke

Efficacy and safety of intracoronary pro-urokinase combined with low-pressure balloon pre-dilatation during percutaneous coronary intervention in patients with anterior ST-segment elevation myocardial infarction. (PubMed, J Cardiothorac Surg) - "Patients with acute anterior STEMI presented more complete epicardial and myocardial reperfusion with adjunctive low-pressure balloon pre-dilatation before intracoronary pro-UK during PCI."

Journal • Cardiovascular • Hematological Disorders • Myocardial Infarction

In silico study of combination thrombolytic therapy with alteplase and mutant pro-urokinase for fibrinolysis in ischemic stroke. (PubMed, Comput Biol Med) - "The synergistic advantage of combining tissue plasminogen activator (tPA) with pro-urokinase (proUK) for thrombolysis has been demonstrated in several in vitro experiments, and a single site proUK mutant (m-proUK) has been developed for better stability in plasma. Therefore, future optimization of dose regimen should focus on limiting the tPA bolus while adjusting m-proUK dosage and infusion rate. Such adjustments could potentially maximize the therapeutic advantages of this combination therapy for ischemic stroke treatment."

Journal • Cardiovascular • Cerebral Hemorrhage • CNS Disorders • Hematological Disorders • Ischemic stroke

Rationale and design of ProUrokinase in Mild IsChemic strokE (PUMICE): a multicentre, prospective, randomised, open-label, blinded-endpoint controlled trial. (PubMed, Stroke Vasc Neurol) - P3 | "This large phase III randomised clinical trial will answer the question of whether thrombolysis is beneficial for acute mild ischemic stroke, and may provide evidence for rhPro-UK in patients had an acute mild ischemic stroke within 4.5 hours of symptom onset."

Journal • Cardiovascular • Cerebral Hemorrhage • Ischemic stroke