Clinical trial NCT05700591: rhPro-UK in Acute Ischaemic Stroke Within 4.5 Hours of Stroke Onset Trial 2(PROST-2)
Official title: A Phase III Trial to Assess the Efficacy and Safety of Recombinant Human Prourokinase in the Treatment of Acute Acute Ischaemic Stroke in 4.5 Hours After Stroke Onset
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Acute Ischemic Stroke
Lead sponsor: Tasly Biopharmaceuticals Co., Ltd.
Sponsor class: INDUSTRY
First posted: 2023-01-26
Enrollment: 1552
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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).


Eligibility criteria: Inclusion Criteria:

1. Clinically diagnosed as acute ischemic stroke (according to the Chinese Guidelines for the Diagnosis and Treatment of Acute Ischemic Stroke 2018).
2. 18 years or older, male or female.
3. NIH Stroke Scale（NIHSS）scores of 4 to 25.
4. Treatment within 4.5 hours after stroke onset.
5. The symptoms of stroke last at least 30 minutes without significant improvement before treatment.
6. Informed consent by patient or by patient's guardians.

Exclusion Criteria:

1. Prestroke modified rankin scale of ≥2.
2. Large areas of hypodense ischaemic changes on baseline CT（Infarction area\> 1/3 of the middle cerebral artery feeding area）.
3. Intracranial hemorrhage.
4. Previous history of intracranial hemorrhage.
5. Severe cerebral trauma or stroke history within 3 months.
6. Intracranial tumor or giant intracranial aneurysm.
7. Intracranial or intraspinal surgery within the past 3 months.
8. Gastrointestinal or urinary bleeding within the past 3 weeks.
9. History of major surgical procedures or severe trauma within the last 2 weeks (investigator evaluation).
10. Puncture in 1 week which can not be oppressed.
11. Active visceral hemorrhage.
12. Aortic arch dissection.
13. Bacterial endocarditis or pericarditis.
14. Planned for thrombectomy.
15. Patients with systolic blood pressure ≥ 185 mmHg or diastolic blood pressure ≥ 110 mmHg after anti-hypertension treatment.
16. High risk of acute hemorrhage include platelet count\<10\^9/L.
17. Received low molecular weight heparin or heparin within 24 hours.
18. Using of thrombin inhibitors or factor Xa inhibitor within the past 48 hours.
19. Using of oral anticoagulant drugs and PT \>15s or INR \>1.7.
20. Patients with epilepsy or other mental disorders that could not be adhered to at the beginning of stroke.
21. Blood glucose \< 2.8 mmol/L or \> 22.2 mmol/L.
22. Allergies to rhPro-UK or rt-PA active ingredients or other components.
23. Pregnant women or beastfeeding women.
24. Participants in other clinical trials within the past month.
25. The investigator believes that the patient is not suitable for the study.

Primary outcomes:
measure: The proportion of patients with excellent functional outcome at 90 days
timeFrame: 90±7 days
Secondary outcomes:
measure: The proportion of patients with independent functional outcome at 90 days
timeFrame: 90±7 days
measure: Functional handicap
timeFrame: 90±7 days
measure: The proportion of patients with neurological improvement at 24 hours
timeFrame: 22-36 hours
measure: The proportion of patients with neurological improvement at 7 days
timeFrame: 7 ±2 days
measure: The change of neurological function at 24 hours
timeFrame: 22-36 hours
measure: The change of neurological function at 7 days
timeFrame: 7 ±2 days
measure: Self-care ability in daily life
timeFrame: 90±7 days
measure: All-cause death within 7 days
timeFrame: 7 days
measure: All-cause death within 90 days
timeFrame: 90 days
measure: Symptomatic intracranial hemorrhage defined as SITS-MOST
timeFrame: 22-36 hours
measure: Symptomatic intracranial hemorrhage defined as ECASSIII
timeFrame: 7 days
measure: Any intracranial hemorrhage
timeFrame: 7 days
measure: Any systematic bleeding event（defined as ISTH）
timeFrame: 7 days
Other outcomes:
Locations:
city: Xuancheng
country: China
facility: Xuancheng People's Hospital
state: Anhui
city: Beijing
country: China
facility: Beijing Tiantan Hospital, Capital Medical University
state: Beijing
city: Beijing
country: China
facility: Xuanwu Hospital, Capital Medical University
state: Beijing
city: Guangdong
country: China
facility: Huizhou First Hospital
state: Guangdong
city: Shaoguan
country: China
facility: Yuebei People's Hospital
state: Guangdong
city: Handan
country: China
facility: Handan Central Hospital
state: Hebei
city: Hengshui
country: China
facility: Hengshui People's Hospital (Harrison International Peace Hospital)
state: Hebei
city: Shijiazhuang
country: China
facility: Hebei General Hospital
state: Hebei
city: Shijiazhuang
country: China
facility: The First Hospital of Hebei Medical University
state: Hebei
city: Shijiazhuang
country: China
facility: The Second Hospital of Hebei Medical University
state: Hebei
city: Xingtai
country: China
facility: Xingtai People's Hospital
state: Hebei
city: Zhangjiakou
country: China
facility: The First Affiliated Hospital of Hebei North University
state: Hebei
city: Daqing
country: China
facility: Daqing Oilfield General Hospital
state: Heilongjiang
city: Daqing
country: China
facility: Daqing People's Hospital
state: Heilongjiang
city: Anyang
country: China
facility: Anyang People's Hospital
state: Henan
city: Luoyang
country: China
facility: Luoyang Central Hospital
state: Henan
city: Nanyang
country: China
facility: First Affiliated Hospital of Nanyang Medical College
state: Henan
city: Nanyang
country: China
facility: Nanshi Hospital of Nanyang
state: Henan
city: Nanyang
country: China
facility: Nanyang Second General Hospital
state: Henan
city: Pingdingshan
country: China
facility: General Hospital of Pingmei Shenma Medical Group
state: Henan
city: Xinxiang
country: China
facility: Xinxiang Central Hospital
state: Henan
city: Zhumadian
country: China
facility: Zhumadian Central Hospital
state: Henan
city: Wuhan
country: China
facility: Tongji Hospital affiliated to Huazhong University of Science and Technology
state: Hubei
city: Wuhan
country: China
facility: Wuhan Fourth Hospital
state: Hubei
city: Xiangyang
country: China
facility: Xiangyang Central Hospital
state: Hubei
city: Baotou
country: China
facility: Baogang Hospital of Inner Mongolia
state: Inner Mongolia
city: Baotou
country: China
facility: Baotou Central Hospital
state: Inner Mongolia
city: Baotou
country: China
facility: The First Affiliated Hospital of Baotou Medical College, Inner Mongolia University of Science & Technology
state: Inner Mongolia
city: Chifeng
country: China
facility: Keshiketeng Hospital of Traditional Chinese Medicine and Mongolian Medicine
state: Inner Mongolia
city: Chifeng
country: China
facility: The Affiliated Hospital of Chifeng University
state: Inner Mongolia
city: Hohhot
country: China
facility: Affiliated Hospital of Inner Mongolia Medical University
state: Inner Mongolia
city: Nanjing
country: China
facility: The Affiliated Hospital of Nanjing University Medical School
state: Jiangsu
city: Xuzhou
country: China
facility: General Hospital of Xuzhou Coal Mining Group
state: Jiangsu
city: Xuzhou
country: China
facility: The Affiliated Hospital of Xuzhou Medical University
state: Jiangsu
city: Xuzhou
country: China
facility: Xuzhou Central Hospital
state: Jiangsu
city: Pingxiang
country: China
facility: Pingxiang People's Hospital
state: Jiangxi
city: Changchun
country: China
facility: Jilin Guowen Hospital
state: Jilin
city: Changchun
country: China
facility: The First Hospital of Jilin University
state: Jilin
city: Changchun
country: China
facility: The Second Hospital of Jilin University
state: Jilin
city: Meihekou
country: China
facility: Meihekou Central Hospital
state: Jilin
city: Siping
country: China
facility: Jilin Neuropsychiatric Hospital
state: Jilin
city: Tonghua
country: China
facility: Tonghua Central Hospital
state: Jilin
city: Anshan
country: China
facility: Ansteel Group General Hospital
state: Liaoning
city: Benxi
country: China
facility: Benxi Central Hospital
state: Liaoning
city: Chaoyang
country: China
facility: Beipiao Central Hospital
state: Liaoning
city: Dalian
country: China
facility: Dalian Municipal Central Hospital
state: Liaoning
city: Fushun
country: China
facility: Fukuang General Hospital of Liaoning Health Industry Group
state: Liaoning
city: Fuxin
country: China
facility: Fuxinkuang General Hospital of Liaoning Health Industry Group
state: Liaoning
city: Jinzhou
country: China
facility: The First Affiliated Hospital of Jinzhou Medical University
state: Liaoning
city: Shenyang
country: China
facility: Central Hospital Affiliated to Shenyang Medical College
state: Liaoning
city: Shenyang
country: China
facility: The First People's Hospital of Shenyang
state: Liaoning
city: Shenyang
country: China
facility: The People's Hospital of Liaoning Province
state: Liaoning
city: Shenyang
country: China
facility: The PLA General Hospital of Northern Theater Command
state: Liaoning
city: Xianyang
country: China
facility: Xianyang Hospital Of Yan'an University
state: Shaanxi
city: Dezhou
country: China
facility: Dezhou People's Hospital
state: Shandong
city: Dezhou
country: China
facility: Tengzhou Central People's Hospital
state: Shandong
city: Dongying
country: China
facility: Shengli Oilfield Central Hospital
state: Shandong
city: Jinan
country: China
facility: Jinan City People's Hospital
state: Shandong
city: Liaocheng
country: China
facility: Liaocheng People's Hospital
state: Shandong
city: Linyi
country: China
facility: Linyi People's Hospital
state: Shandong
city: Tai'an
country: China
facility: Tai'an Central Hospital
state: Shandong
city: Tancheng
country: China
facility: First People's Hospital of Tancheng
state: Shandong
city: Yantai
country: China
facility: Yantai Yuhuangding Hospital
state: Shandong
city: Shanghai
country: China
facility: Huashan Hospital, Fudan University
state: Shanghai
city: Datong
country: China
facility: Sinopharm Tongmei General Hospital
state: Shanxi
city: Linfen
country: China
facility: Linfen Central Hospital
state: Shanxi
city: Linfen
country: China
facility: Linfen People's Hospital
state: Shanxi
city: Chengdu
country: China
facility: West China Hospital of Sichuan University
state: Sichuan
city: Mianyang
country: China
facility: Mianyang Central Hospital
state: Sichuan
city: Tianjin
country: China
facility: Tianjin Huanhu Hospital
state: Tianjin
city: Taizhou
country: China
facility: Taizhou First People's Hospital
state: Zhejiang
city: Taizhou
country: China
facility: Zhejiang Taizhou Hospital
state: Zhejiang
Study officials:
References: