LB 01.3 - Evaluation of Recombinant Human Prourokinase in the Treatment of Acute Pulmonary Embolism (ERUPTE): A Randomized, Single-Blinded, Multicenter, Phase 2 Trial

Background: Recombinant human prourokinase (rhPro-UK), a novel thrombolytic agent, produced in engineered Chinese hamster ovary cells expressing human cDNA, has identical amino acid sequence to natural urokinaseogen. In previous studies on STEMI, rhPro-UK showed superior thrombolytic effect than alteplase. However, its efficacy and safety remain unclear in the treatment of acute pulmonary embolism (aPE).

Aims: To evaluate the efficacy and safety of different intravenous doses of rhPro-UK (40 and 50 mg) in the treatment of patients with aPE.

Methods: In this trial (NCT03108833), 107 aPE patients aged 18-75 years from 21 centers with high or intermediate-to-high risk were equally randomized into three groups receiving intravenous rhPro-UK (40 and 50 mg), or alteplase (at routine dosage). Acute PE was defined as ≤14 days from PE onset to thrombolysis. Patients with contraindications for thrombolysis were excluded. After treatment, patients were followed from 2 hours to 7 days through 30 days. Primary endpoint was the decrease in systolic pulmonary artery pressure (sPAP) at 24 hours (mmHg). All-cause mortality and hemodynamic deterioration within 7 days were safety endpoints.

Results: 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). Two deaths occurred, in 1 patient with rhPro-UK 40 mg and alteplase each.

Conclusion(s): In this trial, rhPro-UK showed similar efficacy in reducing the sPAP to alteplase, but with fewer bleeding events in aPE patients with high or intermediate-to-high risk.