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

Acute Ischemic Stroke Clinical Trial

— 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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT05700591
• Other study ID #: TASLY-B1440-CTP-?c
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: January 29, 2023
• Est. completion date: December 2024

Study information

• Verified date: January 2024
• Source: Tasly Biopharmaceuticals Co., Ltd.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 1552
• Est. completion date: December 2024
• Est. primary completion date: June 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Acute Ischemic Stroke
• Cerebral Infarction
• Ischemia
• Ischemic Stroke
• Stroke

Intervention

Drug:
• rhPro-UK
35 mg, administered intravenously with a bolus of 15 mg within 3 minutes and the remainder by continuous infusion within 30 minutes
• rt-PA
0.9 mg/kg (maximum 90 mg), with 10% administered intravenously as a bolus, followed by 90% infusion within 1 hour

Locations

Country	Name	City	State
China	Ansteel Group General Hospital	Anshan	Liaoning
China	Anyang People's Hospital	Anyang	Henan
China	Baogang Hospital of Inner Mongolia	Baotou	Inner Mongolia
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	Beijing Tiantan Hospital, Capital Medical University	Beijing	Beijing
China	Xuanwu Hospital, Capital Medical University	Beijing	Beijing
China	Benxi Central Hospital	Benxi	Liaoning
China	Jilin Guowen Hospital	Changchun	Jilin
China	The First Hospital of Jilin University	Changchun	Jilin
China	The Second Hospital of Jilin University	Changchun	Jilin
China	Beipiao Central Hospital	Chaoyang	Liaoning
China	West China Hospital of Sichuan University	Chengdu	Sichuan
China	Keshiketeng Hospital of Traditional Chinese Medicine and Mongolian Medicine	Chifeng	Inner Mongolia
China	The Affiliated Hospital of Chifeng University	Chifeng	Inner Mongolia
China	Dalian Municipal Central Hospital	Dalian	Liaoning
China	Daqing Oilfield General Hospital	Daqing	Heilongjiang
China	Daqing People's Hospital	Daqing	Heilongjiang
China	Sinopharm Tongmei General Hospital	Datong	Shanxi
China	Dezhou People's Hospital	Dezhou	Shandong
China	Tengzhou Central People's Hospital	Dezhou	Shandong
China	Shengli Oilfield Central Hospital	Dongying	Shandong
China	Fukuang General Hospital of Liaoning Health Industry Group	Fushun	Liaoning
China	Fuxinkuang General Hospital of Liaoning Health Industry Group	Fuxin	Liaoning
China	Huizhou First Hospital	Guangdong	Guangdong
China	Handan Central Hospital	Handan	Hebei
China	Hengshui People's Hospital (Harrison International Peace Hospital)	Hengshui	Hebei
China	Affiliated Hospital of Inner Mongolia Medical University	Hohhot	Inner Mongolia
China	Jinan City People's Hospital	Jinan	Shandong
China	The First Affiliated Hospital of Jinzhou Medical University	Jinzhou	Liaoning
China	Liaocheng People's Hospital	Liaocheng	Shandong
China	Linfen Central Hospital	Linfen	Shanxi
China	Linfen People's Hospital	Linfen	Shanxi
China	Linyi People's Hospital	Linyi	Shandong
China	Luoyang Central Hospital	Luoyang	Henan
China	Meihekou Central Hospital	Meihekou	Jilin
China	Mianyang Central Hospital	Mianyang	Sichuan
China	The Affiliated Hospital of Nanjing University Medical School	Nanjing	Jiangsu
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	Pingxiang People's Hospital	Pingxiang	Jiangxi
China	Huashan Hospital, Fudan University	Shanghai	Shanghai
China	Yuebei People's Hospital	Shaoguan	Guangdong
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	Hebei General Hospital	Shijiazhuang	Hebei
China	The First Hospital of Hebei Medical University	Shijiazhuang	Hebei
China	The Second Hospital of Hebei Medical University	Shijiazhuang	Hebei
China	Jilin Neuropsychiatric Hospital	Siping	Jilin
China	Tai'an Central Hospital	Tai'an	Shandong
China	Taizhou First People's Hospital	Taizhou	Zhejiang
China	Zhejiang Taizhou Hospital	Taizhou	Zhejiang
China	First People's Hospital of Tancheng	Tancheng	Shandong
China	Tianjin Huanhu Hospital	Tianjin	Tianjin
China	Tonghua Central Hospital	Tonghua	Jilin
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	Xianyang Hospital Of Yan'an University	Xianyang	Shaanxi
China	Xingtai People's Hospital	Xingtai	Hebei
China	Xinxiang Central Hospital	Xinxiang	Henan
China	Xuancheng People's Hospital	Xuancheng	Anhui
China	General Hospital of Xuzhou Coal Mining Group	Xuzhou	Jiangsu
China	The Affiliated Hospital of Xuzhou Medical University	Xuzhou	Jiangsu
China	Xuzhou Central Hospital	Xuzhou	Jiangsu
China	Yantai Yuhuangding Hospital	Yantai	Shandong
China	The First Affiliated Hospital of Hebei North University	Zhangjiakou	Hebei
China	Zhumadian Central Hospital	Zhumadian	Henan

Sponsors (1)

Lead Sponsor	Collaborator
Tasly Biopharmaceuticals Co., Ltd.

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	90±7 days
Secondary	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.	90±7 days
Secondary	Functional handicap	The distribution of the modified Rankin scale(which ranges from 0 [no symptoms] to 6 [death]) at 90 days	90±7 days
Secondary	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.	22-36 hours
Secondary	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.	7 ±2 days
Secondary	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.	22-36 hours
Secondary	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.	7 ±2 days
Secondary	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	90±7 days
Secondary	All-cause death within 7 days		7 days
Secondary	All-cause death within 90 days		90 days
Secondary	Symptomatic intracranial hemorrhage defined as SITS-MOST		22-36 hours
Secondary	Symptomatic intracranial hemorrhage defined as ECASSIII		7 days
Secondary	Any intracranial hemorrhage		7 days
Secondary	Any systematic bleeding event(defined as ISTH)		7 days