rhPro-UK in Acute Ischaemic Stroke Within 4.5 Hours of Stroke Onset Trial 2(PROST-2)

Summary

Intravenous thrombolysis is the first-line therapy in patients with acute ischemic stroke within 4·5 hours of symptom onset, and recombinant tissue plasminogen activator (alteplase) is the preferred thrombolytic agent for this purpose. RhPro-UK is a specific plasminogen activator. rhPro-UK only acts on occlusive thrombus and has little effect on hemostatic thrombus. In addition, rhPro-UK does not form covalent complexes with protease inhibitors in plasma, so the concentrations of rhpro-UK and protease inhibitors in the blood do not decrease compared with alteplase. Therefore, rhPro-UK therapies have a potential advantage of less systemic bleeding in treated subjects. Data from several previous studies suggest that rhPro-UK is efficacious when used to treat patients with acute myocardial infarction. On April 2, 2011, rhPro-UK injection was approved by the National Medical Products Administration to treat acute myocardial infarction. Since then, rhPro-UK has been widely used to treat myocardial infarction in China. Since 2016, a phase 2 clinical trial was carried to explore the dosing of rhPro-UK in patients with acute ischemic stroke, followed by another study with a sample size of 680 patients to initially validate the efficacy and safety of the proposed dose of 35mg. The results of these studies suggested that rhPro-UK was effective, and there were no safety concerns. To further prove the efficacy and safety of rhPro-UK in patients with acute ischemic stroke, investigators conducted this phase 3 study (PROST-2).

Timeline

Start

2023-01-29

Primary completion

2024-03-14

Completion

2024-03-14

Publications

• Li S, Gu HQ, Feng B, Li H, Wang X, Dong Q, Fan D, Xu Y, Zhu S, Dai H, Wei Y, Wang Z, Lu G, Ma Y, Li Z, Wang Y, Meng X, Zhao X, Liu L, Wang Y; PROST-2 investigators. Safety and efficacy of intravenous recombinant human prourokinase for acute ischaemic stroke within 4.5 h after stroke onset (PROST-2): a phase 3, open-label, non-inferiority, randomised controlled trial. Lancet Neurol. 2025 Jan;24(1):33-41. doi: 10.1016/S1474-4422(24)00436-8. Epub 2024 Nov 29.
• Li S, Gu HQ, Feng B, Dong Q, Fan D, Xu Y, Zhu S, Wang Y. RhPro-UK in acute ischemic stroke within 4.5 h 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. Int J Stroke. 2024 Dec;19(10):1182-1187. doi: 10.1177/17474930241265654. Epub 2024 Aug 3.

Drugs

Indications