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

NCT05700591
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Phase
Phase 3
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Recruitment status
Completed
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Participants
1,552
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Lead sponsor
Tasly Biopharmaceuticals Co., Ltd.
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Start date
2023-01-29
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Number of sites
72
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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).
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Acronym
PROST-2
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Short title
rhPro-UK in Acute Ischaemic Stroke Within 4.5 Hours of Stroke Onset Trial 2(PROST-2)
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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
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Control arm
Active comparator
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Registry reports results
No
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Listing at source
Listed
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Recruitment status
Completed
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Phase
Phase 3
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Study type
Interventional
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Completion date
2024-03-14
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First posted
2023-01-26
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Registry last updated
2024-07-26
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Primary completion date
2024-03-14
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Start date
2023-01-29
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Actual participants
1,552
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Participants
1,552
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Participant count basis
Actual
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Protocol amendments
2
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Number of sites
72
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Data monitoring committee
Yes
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Registry sponsor category
Industry
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Lead sponsor
Tasly Biopharmaceuticals Co., Ltd.
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Source registry
ClinicalTrials.gov
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Registry ID
NCT05700591
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ClinicalTrials.gov ID
NCT05700591
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Registry record
Open registry record
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Allocation
Randomised
Model
Parallel groups
Purpose
Treatment
Masking
Single masking
Masked roles
Outcome assessors
Sources for study design
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  1. The proportion of patients with excellent functional outcome at 90 days

    Timeframe: 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.

  1. The proportion of patients with independent functional outcome at 90 days

    Timeframe: 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.

  2. Functional handicap

    Timeframe: 90±7 days

    The distribution of the modified Rankin scale(which ranges from 0 \[no symptoms\] to 6 \[death\]) at 90 days

  3. The proportion of patients with neurological improvement at 24 hours

    Timeframe: 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.

  4. The proportion of patients with neurological improvement at 7 days

    Timeframe: 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.

  5. The change of neurological function at 24 hours

    Timeframe: 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.

  6. The change of neurological function at 7 days

    Timeframe: 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.

  7. Self-care ability in daily life

    Timeframe: 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

  8. All-cause death within 7 days

    Timeframe: 7 days

  9. All-cause death within 90 days

    Timeframe: 90 days

  10. Symptomatic intracranial hemorrhage defined as SITS-MOST

    Timeframe: 22-36 hours

  11. Symptomatic intracranial hemorrhage defined as ECASSIII

    Timeframe: 7 days

  12. Any intracranial hemorrhage

    Timeframe: 7 days

  13. Any systematic bleeding event（defined as ISTH）

    Timeframe: 7 days

Sources for outcomes
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Sex
All
Age groups
Adults, Older adults
Minimum age
18 Years
Healthy volunteers
No

  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.

  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.
Sources for eligibility
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  • Xuancheng People's HospitalXuancheng, China
  • Beijing Tiantan Hospital, Capital Medical UniversityBeijing, China
  • Xuanwu Hospital, Capital Medical UniversityBeijing, China
  • Huizhou First HospitalGuangdong, China
  • Yuebei People's HospitalShaoguan, China
  • Handan Central HospitalHandan, China
  • Hengshui People's Hospital (Harrison International Peace Hospital)Hengshui, China
  • Hebei General HospitalShijiazhuang, China
  • The First Hospital of Hebei Medical UniversityShijiazhuang, China
  • The Second Hospital of Hebei Medical UniversityShijiazhuang, China
  • Xingtai People's HospitalXingtai, China
  • The First Affiliated Hospital of Hebei North UniversityZhangjiakou, China
  • Daqing Oilfield General HospitalDaqing, China
  • Daqing People's HospitalDaqing, China
  • Anyang People's HospitalAnyang, China
  • Luoyang Central HospitalLuoyang, China
  • First Affiliated Hospital of Nanyang Medical CollegeNanyang, China
  • Nanshi Hospital of NanyangNanyang, China
  • Nanyang Second General HospitalNanyang, China
  • General Hospital of Pingmei Shenma Medical GroupPingdingshan, China
  • Xinxiang Central HospitalXinxiang, China
  • Zhumadian Central HospitalZhumadian, China
  • Tongji Hospital affiliated to Huazhong University of Science and TechnologyWuhan, China
  • Wuhan Fourth HospitalWuhan, China
  • Xiangyang Central HospitalXiangyang, China

And 47 more, listed on the interactive page.

Sources for sites
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Sources for references
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Related records

Drugs (1)

Lead sponsors (1)

Conditions (2)

Targets (1)