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

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.