Evaluation of recombinant human prourokinase for acute pulmonary embolism: A phase 2, randomized clinical trial

Clinical Snapshot

Key Findings

• P Value: p = 0.04 for bleeding comparison only

• Effect Size: 40mg rhPro-UK: -13.40 mmHg; 50mg rhPro-UK: -15.42 mmHg; rt-PA: -16.02 mmHg

• Primary Outcome: Reduction in systolic pulmonary artery pressure at 24 hours

• Nnt Or Sensitivity: Not calculable from available data

• Confidence Interval: 40mg: -24.10 to -2.71; 50mg: -25.93 to -4.91; rt-PA: -25.53 to -6.51

Clinical Application

Limited by availability of rhPro-UK and requirement for specialised monitoring Would require TGA approval and PBS listing consideration. Current Australian guidelines favour alteplase for thrombolysis in PE. Cost-effectiveness analysis needed for PBS submission. Adults with high or intermediate-to-high risk acute pulmonary embolism in tertiary care settings

Abstract

BACKGROUND: Recombinant human prourokinase (rhPro-UK) is a novel plasminogen activator under investigation for acute pulmonary embolism (aPE). We aimed to explore the efficacy and safety of rhPro-UK vs. alteplase (recombinant tissue plasminogen activator [rt-PA]) in patients with aPE. METHODS: In this phase 2, randomized, single-blind, multicenter, active-controlled, randomized trial involved eighteen centers from university-affiliated tertiary hospitals across China. Patients aged 18-75 years with high or intermediate-to-high risk aPE were randomized to receive intravenous rhPro-UK (40 mg, n = 37; 50 mg, n = 35) or rt-PA (n = 35) and were followed for 7-30 days. The primary efficacy outcome was the change from baseline in systolic pulmonary artery pressure (sPAP) at 24 h post-treatment. Secondary outcomes include changes in right ventricular function parameters. Safety outcomes include all-cause mortality, recurrent PE, hemodynamic deterioration within 7 days, and bleeding events within 30 days. FINDINGS: All treatment groups showed a reduction in sPAP at 24 h (mean change: 40 mg rhPro-UK, -13.40 mmHg [95% confidence interval (CI): -24.10 to -2.71]; 50 mg rhPro-UK, -15.42 mmHg [95% CI: -25.93 to -4.91], and rt-PA: -16.02 mmHg [95% CI: -25.53 to -6.51]), with improvements sustained through 30 days. The incidence of non-major bleeding events was numerically lower in the rhPro-UK groups (40 mg: 63.9%; 50 mg: 55.6%) compared to the rt-PA group (82.9%; p = 0.04). Two deaths occurred, each in the 40 mg rhPro-UK group and rt-PA group. CONCLUSION: rhPro-UK tended to result in early hemodynamic improvement comparable to rt-PA and seemed to have a numerically lower risk of non-major bleeding events. The ClinicalTrials.gov identifier is NCT03108833. FUNDING: This work was funded by Tasly Biopharmaceuticals Co., Ltd.

References

1. 1.Cheng, C. Y., Fan, F. L., Wu, B. X., Hua, L., Zhou, H. M., Ying, K. J., Zheng, Z. Q., Zhang, W. H., Mi, Y. H., Xie, W. P., Yu, Z. X., Liu, R., Wang, D. L., Xu, X. Q., & Jing, Z. C. (2026). Evaluation of recombinant human prourokinase for acute pulmonary embolism: A phase 2, randomized clinical trial. Med (New York, N.Y.). https://doi.org/10.1016/j.medj.2026.101068