rhPro-UK in Acute Ischaemic Stroke Within 4.5 Hours of Stroke Onset Trial 2(PROST-2)
- Registration Number
- NCT05700591
- Lead Sponsor
- Tasly Biopharmaceuticals Co., Ltd.
- Brief 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).
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 1552
- Clinically diagnosed as acute ischemic stroke (according to the Chinese Guidelines for the Diagnosis and Treatment of Acute Ischemic Stroke 2018).
- 18 years or older, male or female.
- NIH Stroke Scale（NIHSS）scores of 4 to 25.
- Treatment within 4.5 hours after stroke onset.
- The symptoms of stroke last at least 30 minutes without significant improvement before treatment.
- Informed consent by patient or by patient's guardians.
- Prestroke modified rankin scale of ≥2.
- Large areas of hypodense ischaemic changes on baseline CT（Infarction area> 1/3 of the middle cerebral artery feeding area）.
- Intracranial hemorrhage.
- Previous history of intracranial hemorrhage.
- Severe cerebral trauma or stroke history within 3 months.
- Intracranial tumor or giant intracranial aneurysm.
- Intracranial or intraspinal surgery within the past 3 months.
- Gastrointestinal or urinary bleeding within the past 3 weeks.
- History of major surgical procedures or severe trauma within the last 2 weeks (investigator evaluation).
- Puncture in 1 week which can not be oppressed.
- Active visceral hemorrhage.
- Aortic arch dissection.
- Bacterial endocarditis or pericarditis.
- Planned for thrombectomy.
- Patients with systolic blood pressure ≥ 185 mmHg or diastolic blood pressure ≥ 110 mmHg after anti-hypertension treatment.
- High risk of acute hemorrhage include platelet count<10^9/L.
- Received low molecular weight heparin or heparin within 24 hours.
- Using of thrombin inhibitors or factor Xa inhibitor within the past 48 hours.
- Using of oral anticoagulant drugs and PT >15s or INR >1.7.
- Patients with epilepsy or other mental disorders that could not be adhered to at the beginning of stroke.
- Blood glucose < 2.8 mmol/L or > 22.2 mmol/L.
- Allergies to rhPro-UK or rt-PA active ingredients or other components.
- Pregnant women or beastfeeding women.
- Participants in other clinical trials within the past month.
- The investigator believes that the patient is not suitable for the study.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description rhPro-UK rhPro-UK Recombinant Human Pro-urokinase (rhPro-UK) rt-PA rt-PA Alteplase(rt-PA)
- Primary Outcome Measures
Name Time Method The proportion of patients with excellent functional outcome at 90 days 90±7 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.
- Secondary Outcome Measures
Name Time Method All-cause death within 7 days 7 days Symptomatic intracranial hemorrhage defined as ECASSIII 7 days The proportion of patients with neurological improvement at 24 hours 22-36 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.
Self-care ability in daily life 90±7 days 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
The proportion of patients with independent functional outcome at 90 days 90±7 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.
Functional handicap 90±7 days The distribution of the modified Rankin scale(which ranges from 0 \[no symptoms\] to 6 \[death\]) at 90 days
The change of neurological function at 7 days 7 ±2 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.
Any intracranial hemorrhage 7 days Any systematic bleeding event（defined as ISTH） 7 days The change of neurological function at 24 hours 22-36 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.
All-cause death within 90 days 90 days Symptomatic intracranial hemorrhage defined as SITS-MOST 22-36 hours The proportion of patients with neurological improvement at 7 days 7 ±2 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.
Trial Locations
- Locations (72)
Huizhou First Hospital
🇨🇳Guangdong, Guangdong, China
Tengzhou Central People's Hospital
🇨🇳Dezhou, Shandong, China
Shengli Oilfield Central Hospital
🇨🇳Dongying, Shandong, China
Huashan Hospital, Fudan University
🇨🇳Shanghai, Shanghai, China
Tianjin Huanhu Hospital
🇨🇳Tianjin, Tianjin, China
Taizhou First People's Hospital
🇨🇳Taizhou, Zhejiang, China
Beijing Tiantan Hospital, Capital Medical University
🇨🇳Beijing, Beijing, China
Xuancheng People's Hospital
🇨🇳Xuancheng, Anhui, China
Yuebei People's Hospital
🇨🇳Shaoguan, Guangdong, China
Xuanwu Hospital, Capital Medical University
🇨🇳Beijing, Beijing, China
Handan Central Hospital
🇨🇳Handan, Hebei, China
Hengshui People's Hospital (Harrison International Peace Hospital)
🇨🇳Hengshui, Hebei, China
Hebei General Hospital
🇨🇳Shijiazhuang, Hebei, China
The Second Hospital of Hebei Medical University
🇨🇳Shijiazhuang, Hebei, China
The First Hospital of Hebei Medical University
🇨🇳Shijiazhuang, Hebei, China
Xingtai People's Hospital
🇨🇳Xingtai, Hebei, China
The First Affiliated Hospital of Hebei North University
🇨🇳Zhangjiakou, Hebei, China
Daqing Oilfield General Hospital
🇨🇳Daqing, Heilongjiang, China
Daqing People's Hospital
🇨🇳Daqing, Heilongjiang, China
Luoyang Central Hospital
🇨🇳Luoyang, Henan, China
Anyang People's Hospital
🇨🇳Anyang, Henan, China
First Affiliated Hospital of Nanyang Medical College
🇨🇳Nanyang, Henan, China
Nanshi Hospital of Nanyang
🇨🇳Nanyang, Henan, China
Nanyang Second General Hospital
🇨🇳Nanyang, Henan, China
General Hospital of Pingmei Shenma Medical Group
🇨🇳Pingdingshan, Henan, China
Xinxiang Central Hospital
🇨🇳Xinxiang, Henan, China
Zhumadian Central Hospital
🇨🇳Zhumadian, Henan, China
Tongji Hospital affiliated to Huazhong University of Science and Technology
🇨🇳Wuhan, Hubei, China
Wuhan Fourth Hospital
🇨🇳Wuhan, Hubei, China
Xiangyang Central Hospital
🇨🇳Xiangyang, Hubei, China
Baotou Central Hospital
🇨🇳Baotou, Inner Mongolia, China
The First Affiliated Hospital of Baotou Medical College, Inner Mongolia University of Science & Technology
🇨🇳Baotou, Inner Mongolia, China
Baogang Hospital of Inner Mongolia
🇨🇳Baotou, Inner Mongolia, China
Keshiketeng Hospital of Traditional Chinese Medicine and Mongolian Medicine
🇨🇳Chifeng, Inner Mongolia, China
Affiliated Hospital of Inner Mongolia Medical University
🇨🇳Hohhot, Inner Mongolia, China
The Affiliated Hospital of Chifeng University
🇨🇳Chifeng, Inner Mongolia, China
The Affiliated Hospital of Nanjing University Medical School
🇨🇳Nanjing, Jiangsu, China
General Hospital of Xuzhou Coal Mining Group
🇨🇳Xuzhou, Jiangsu, China
Pingxiang People's Hospital
🇨🇳Pingxiang, Jiangxi, China
Xuzhou Central Hospital
🇨🇳Xuzhou, Jiangsu, China
The Affiliated Hospital of Xuzhou Medical University
🇨🇳Xuzhou, Jiangsu, China
Jilin Guowen Hospital
🇨🇳Changchun, Jilin, China
The First Hospital of Jilin University
🇨🇳Changchun, Jilin, China
Meihekou Central Hospital
🇨🇳Meihekou, Jilin, China
The Second Hospital of Jilin University
🇨🇳Changchun, Jilin, China
Jilin Neuropsychiatric Hospital
🇨🇳Siping, Jilin, China
Tonghua Central Hospital
🇨🇳Tonghua, Jilin, China
Beipiao Central Hospital
🇨🇳Chaoyang, Liaoning, China
Ansteel Group General Hospital
🇨🇳Anshan, Liaoning, China
Benxi Central Hospital
🇨🇳Benxi, Liaoning, China
Dalian Municipal Central Hospital
🇨🇳Dalian, Liaoning, China
Fukuang General Hospital of Liaoning Health Industry Group
🇨🇳Fushun, Liaoning, China
Fuxinkuang General Hospital of Liaoning Health Industry Group
🇨🇳Fuxin, Liaoning, China
The First Affiliated Hospital of Jinzhou Medical University
🇨🇳Jinzhou, Liaoning, China
Central Hospital Affiliated to Shenyang Medical College
🇨🇳Shenyang, Liaoning, China
The First People's Hospital of Shenyang
🇨🇳Shenyang, Liaoning, China
The People's Hospital of Liaoning Province
🇨🇳Shenyang, Liaoning, China
The PLA General Hospital of Northern Theater Command
🇨🇳Shenyang, Liaoning, China
Xianyang Hospital Of Yan'an University
🇨🇳Xianyang, Shaanxi, China
Dezhou People's Hospital
🇨🇳Dezhou, Shandong, China
Jinan City People's Hospital
🇨🇳Jinan, Shandong, China
Linyi People's Hospital
🇨🇳Linyi, Shandong, China
Liaocheng People's Hospital
🇨🇳Liaocheng, Shandong, China
First People's Hospital of Tancheng
🇨🇳Tancheng, Shandong, China
Yantai Yuhuangding Hospital
🇨🇳Yantai, Shandong, China
Tai'an Central Hospital
🇨🇳Tai'an, Shandong, China
Sinopharm Tongmei General Hospital
🇨🇳Datong, Shanxi, China
Linfen People's Hospital
🇨🇳Linfen, Shanxi, China
Linfen Central Hospital
🇨🇳Linfen, Shanxi, China
West China Hospital of Sichuan University
🇨🇳Chengdu, Sichuan, China
Mianyang Central Hospital
🇨🇳Mianyang, Sichuan, China
Zhejiang Taizhou Hospital
🇨🇳Taizhou, Zhejiang, China