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).
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
SINGLE
Enrollment
1,552
Xuancheng People's Hospital
Xuancheng, Anhui, China
Beijing Tiantan Hospital, Capital Medical University
Beijing, Beijing Municipality, China
Xuanwu Hospital, Capital Medical University
Beijing, Beijing Municipality, China
Huizhou First Hospital
Guangdong, Guangdong, China
Yuebei People's Hospital
Shaoguan, Guangdong, China
The proportion of patients with excellent functional outcome at 90 days
A score of 0 or 1 on the modified Rankin scale(which ranges from 0 \[no symptoms\] to 6 \[death\]) at 90 days indicated an excellent functional outcome.
Time frame: 90±7 days
The proportion of patients with independent functional outcome at 90 days
A score of 0-2 on the modified Rankin scale(which ranges from 0 \[no symptoms\] to 6 \[death\]) at 90 days indicated an independent functional outcome.
Time frame: 90±7 days
Functional handicap
The distribution of the modified Rankin scale(which ranges from 0 \[no symptoms\] to 6 \[death\]) at 90 days
Time frame: 90±7 days
The proportion of patients with neurological improvement at 24 hours
A reduction in NIHSS score of ≥4 or a score of 0-1 indicated neurological improvement. Total scores on the NIHSS range from 0 to 42, with higher values reflecting more severe cerebral infarcts.
Time frame: 22-36 hours
The proportion of patients with neurological improvement at 7 days
A reduction in NIHSS score of ≥4 or a score of 0-1 indicated neurological improvement. Total scores on the NIHSS range from 0 to 42, with higher values reflecting more severe cerebral infarcts.
Time frame: 7 ±2 days
The change of neurological function at 24 hours
NIHSS score was used to assess neurological function. Total scores on the NIHSS range from 0 to 42, with higher values reflecting more severe cerebral infarcts.
Time frame: 22-36 hours
The change of neurological function at 7 days
NIHSS score was used to assess neurological function. Total scores on the NIHSS range from 0 to 42, with higher values reflecting more severe cerebral infarcts.
Time frame: 7 ±2 days
Self-care ability in daily life
The Barthel Index(which ranges from 0\[complete dependence on help with activities of daily living\] to 100\[independence\]) of 95-100 at 90 days
Time frame: 90±7 days
All-cause death within 7 days
Time frame: 7 days
All-cause death within 90 days
Time frame: 90 days
Symptomatic intracranial hemorrhage defined as SITS-MOST
Time frame: 22-36 hours
Symptomatic intracranial hemorrhage defined as ECASSIII
Time frame: 7 days
Any intracranial hemorrhage
Time frame: 7 days
Any systematic bleeding event(defined as ISTH)
Time frame: 7 days
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Handan Central Hospital
Handan, Hebei, China
Hengshui People's Hospital (Harrison International Peace Hospital)
Hengshui, Hebei, China
Hebei General Hospital
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The First Hospital of Hebei Medical University
Shijiazhuang, Hebei, China
The Second Hospital of Hebei Medical University
Shijiazhuang, Hebei, China
...and 62 more locations