Clinical trial NCT05507645: ProUrokinase for Mild Ischemic Cerebrovascular Events (PUMICE)
Official title: Recombinant Human Prourokinase（rhPro-UK）for Injection Versus Standard Medical Treatment for Acute Mild Ischemic Stroke (NIHSS≤5) Within 4.5 Hours After Symptom Onset
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Ischemic Stroke
Mild
Thrombosis
Lead sponsor: Beijing Tiantan Hospital
Sponsor class: OTHER
First posted: 2022-08-19
Enrollment: 1446
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: A multicenter, prospective, randomized, open-label, blinded-endpoint (PROBE) controlled trial
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to investigate the safety and efficacy of rhPro-UK (35mg) versus standard medical treatment in acute mild ischemic stroke within 4.5 hours of symptom onset.

Detailed description: After being informed about the study and potential risks, patients who meet the eligibility requirements will be randomized to recombinant human Prourokinase for injection (rhPro-UK) or standard medical treatment in a 1:1 ratio. Written informed consent will be needed.

Eligibility criteria: Inclusion Criteria:

1. Age ≥18 years, any gender;
2. Acute ischemic stroke symptom onset within 4.5 hours prior to enrollment; onset time refers to 'last-seen normal time';
3. Pre-stroke mRS score≤ 1;
4. Baseline NIHSS ≤ 5 (both included);
5. Written informed consent from patients or their legally authorized representatives

Exclusion Criteria:

1. Rapidly improving symptoms at the discretion of the investigator;
2. Intended to proceed to endovascular treatment during 90 days (including mechanical thrombectomy, stent insertion or balloon expansion);
3. Allergy to rhPro-UK and it's components (human albumin, mannitol);
4. NIHSS consciousness score 1a \>2, or epileptic seizure, hemiplegia after seizures (Todd's palsy) or combined with other nervous/mental illness unable to cooperate or unwilling to cooperate;
5. Persistent blood pressure elevation (systolic ≥180 mmHg or diastolic ≥100 mmHg), despite blood pressure lowering treatment;
6. Blood glucose \<2.8 or \>22.2 mmol/L (point of care glucose testing is acceptable);
7. Active internal bleeding or at high risk of bleeding, e.g.: Major surgery, trauma or gastrointestinal or urinary tract haemorrhage within the previous 21 days, or arterial puncture at a non-compressible site within the previous 7 days;
8. Any known impairment in coagulation due to comorbid disease or anticoagulant use. If on warfarin, then INR \>1.7 or prothrombin time \>15 seconds; if use of any direct thrombin inhibitors or direct factor Xa inhibitors or new oral anticoagulants (NOAC) during the last 48 hours unless reversal of effect can be achieved with a reversal agent (by idarucizumab) or sensitivity laboratory test values greater than the upper limit of normal (eg, activated partial thromboplastin time (aPTT), international normalized ratio (INR), platelet count, thrombin time (TT), or appropriate factor Xa activity assay); if on any full dose heparin/heparinoid during the last 24 hours or with an elevated aPTT greater than the upper limit of normal;
9. Known defect of platelet function or platelet count below 100,000/mm3 (but patients on antiplatelet agents can be included);
10. Ischemic stroke or myocardial infarction in previous 3 months, previous intracranial haemorrhage, severe traumatic brain injury or intracranial or intraspinal operation in previous 3 months, or known intracranial neoplasm (except for neuroectodermal tumors, such as meningiomas), arteriovenous malformation or giant aneurysm;
11. Any terminal illness such that patient would not be expected to survive more than 1 year
12. Large cerebral infarction (infarct size \> 1/3 MCA territory) on CT or MRI;
13. Acute or past intracerebral hemorrhage (ICH) identified by CT or MRI (including intraparenchymal hemorrhage, intraventricular hemorrhage, subarachnoid hemorrhage, subdural/epidural hematoma);
14. Pregnant women, nursing mothers, or reluctant to agree taking effective contraceptive measures during the period of trial subjects;
15. Any condition that, in the judgment of the investigator could impose hazards to the patient if study therapy is initiated or affect the participation of the patient in the study;
16. Participation in other interventional clinical trials within the previous 3 months.

Primary outcomes:
measure: The modified Rankin Scale score (mRS) ≤ 1 at 90 days
timeFrame: 90 days
Secondary outcomes:
measure: Ordinal distribution of mRS at 90 days
timeFrame: 90 days
measure: mRS score ≤ 2 at 90 days
timeFrame: 90 days
measure: Early neurological functional improvement
timeFrame: 24 hours
measure: Barthel index of 75-100 points at 90 days
timeFrame: 90 days
measure: Quality of Life (EQ-5D-5L) at 90 days
timeFrame: 90 days
measure: Activities of Daily Living (Lawton IADL) at 90 days
timeFrame: 90 days
measure: Symptomatic intracranial hemorrhage within 36 hours
timeFrame: 36 hours
measure: All-cause death at 90 days
timeFrame: 90 days
measure: Systematic bleeding at 90 days
timeFrame: 90 days
measure: Adverse events (AEs)/ serious adverse events (SAEs) within 90 days
timeFrame: 90 days
Other outcomes:
Locations:
city: Fuyang
country: China
facility: Taihe Hospital of Traditional Chinese Medicine
state: Anhui
city: Hefei
country: China
facility: Lujiang County People's Hospital,Anhui Province
state: Anhui
city: Beijing
country: China
facility: Beijing Tiantan Hospital, Capital Medical University
state: Beijing
city: Beijing
country: China
facility: The First Hospital of Fangshan District, Beijing
state: Beijing
city: Chongqing
country: China
facility: Chongqing Sanbo Chang 'an Hospital
state: Chongqing
city: Dingxi
country: China
facility: Dingxi People's Hospital
state: Gansu
city: Jiuquan
country: China
facility: Jiuquan City People's Hospital
state: Gansu
city: Guangzhou
country: China
facility: Guangdong Second Provincial General Hospital
state: Guangdong
city: Heyuan
country: China
facility: Heyuan People's Hospital
state: Guangdong
city: Maoming
country: China
facility: People's Hospital of Huazhou
state: Guangdong
city: Zhanjiang
country: China
facility: Wuchuan People's Hospital
state: Guangdong
city: Nanning
country: China
facility: Wuming Hospital of Guangxi Medical University
state: Guangxi
city: Guiyang
country: China
facility: The Second People's Hospital of Guiyang
state: Guizhou
city: Kaili
country: China
facility: The Second Affiliated Hospital of Guizhou Medical University
state: Guizhou
city: Kaili
country: China
facility: The People's Hospital of the Qiandongnan Miao and Dong Autonomous Prefecture
state: Guizhou
city: Baoding
country: China
facility: Affiliated Hospital of Hebei University
state: Hebei
city: Baoding
country: China
facility: Hebei Tang County People Hospital
state: Hebei
city: Chengde
country: China
facility: Chengde Central Hospital
state: Hebei
city: Chengde
country: China
facility: Long Hua Xian Yi Yuan
state: Hebei
city: Chengde
country: China
facility: Fengning Manchu Autonomous County Hospital
state: Hebei
city: Handan
country: China
facility: Wei Xian Ren Min Yi Yuan
state: Hebei
city: Qinhuangdao
country: China
facility: The People's Hospital of Changli County
state: Hebei
city: Qinhuangdao
country: China
facility: The Second Hospital of Qinhuangdao
state: Hebei
city: Shijiazhuang
country: China
facility: Xingtang People's Hospital
state: Hebei
city: Shijiazhuang
country: China
facility: Yuanshi Hospital of Traditional Chinese Medicine
state: Hebei
city: Shijiazhuang
country: China
facility: The Second Hospital of Xinji
state: Hebei
city: Shijiazhuang
country: China
facility: Xinji Hospital of T.C.M
state: Hebei
city: Tangshan
country: China
facility: Linxi Hospital of Kailuan General Hospital
state: Hebei
city: Tangshan
country: China
facility: Luanzhou People's Hospital
state: Hebei
city: Tangshan
country: China
facility: Tangshan Guye Traditional Chinese Medicine Hospital
state: Hebei
city: Tangshan
country: China
facility: Tangshan Fengnan District Hospital
state: Hebei
city: Tangshan
country: China
facility: Yu Tian Xian Zhong Yi Yi Yuan
state: Hebei
city: Tangshan
country: China
facility: Zunhua People's Hospital
state: Hebei
city: Tangshan
country: China
facility: The People's Hospital of Qianxi County
state: Hebei
city: Xingtai
country: China
facility: Weixian People's Hospital
state: Hebei
city: Xingtai
country: China
facility: The Greatwall Hospital
state: Hebei
city: Jiamusi
country: China
facility: Center Hospital·Jiamusi
state: Heilongjiang
city: Jiaozuo
country: China
facility: Central Hospital·Jiaozuo
state: Henan
city: Jiaozuo
country: China
facility: The Second People's Hospital of Jiaozuo
state: Henan
city: Jiyuan
country: China
facility: Jiyuan Hospital of Traditional Chinese Medicine
state: Henan
city: Luoyang
country: China
facility: Luoyang First People's Hospital
state: Henan
city: Nanyang
country: China
facility: Tanghe County People's Hospital
state: Henan
city: Puyang
country: China
facility: Puyang Oilfield General Hospital
state: Henan
city: Puyang
country: China
facility: Chinese Medicine Hospital of Puyang
state: Henan
city: Sanmenxia
country: China
facility: The First People Hospital of Lingbao
state: Henan
city: Shangqiu
country: China
facility: The Shangqiu First People's Hospital
state: Henan
city: Shangqiu
country: China
facility: Xiayi County People's Hospital
state: Henan
city: Shangqiu
country: China
facility: The People's Hospital of Yongcheng
state: Henan
city: Xinyang
country: China
facility: People's Hospital of Xixian
state: Henan
city: Xinyang
country: China
facility: Guang Shan County People's Hospital
state: Henan
city: Zhengzhou
country: China
facility: Xinmi Hospital of T.C.M
state: Henan
city: Zhoukou
country: China
facility: Taikang Xian People's Hospital
state: Henan
city: Changsha
country: China
facility: Liuyang Jili Hospital
state: Hunan
city: Baotou
country: China
facility: Baotou City Central Hospital
state: Inner Mongolia
city: Huai'an
country: China
facility: Huai'an Second People's Hospital
state: Jiangsu
city: Yancheng
country: China
facility: Funing People's Hospital
state: Jiangsu
city: Jilin
country: China
facility: Jilin People's Hospital
state: Jilin
city: Tonghua
country: China
facility: Tonghua City vascular disease Hospital and Dongchang District People's Hospital
state: Jilin
city: Tonghua
country: China
facility: Meihekou Central Hospital
state: Jilin
city: Anshan
country: China
facility: Haicheng Hospital of T.C.M
state: Liaoning
city: Dalian
country: China
facility: Dalian Lvshunkou District Traditional Chinese Medicine Hospital
state: Liaoning
city: Fushun
country: China
facility: General Hospital of Fushun Mining Bureau of Liaoning Health Industry Group
state: Liaoning
city: Huludao
country: China
facility: Huludao Center Hospital
state: Liaoning
city: Huludao
country: China
facility: The Second People's Hospital of Huludao
state: Liaoning
city: Shenyang
country: China
facility: The Fourth Affiliated Hospital of China Medical University
state: Liaoning
city: Weinan
country: China
facility: Weinan Central Hospital
state: Shaanxi
city: Dezhou
country: China
facility: People's Hospital of Qihe County
state: Shandong
city: Dezhou
country: China
facility: Ningjin People's Hospital
state: Shandong
city: Liaocheng
country: China
facility: Liaocheng People's Hospital
state: Shandong
city: Liaocheng
country: China
facility: Liaocheng Third People's Hospital
state: Shandong
city: Liaocheng
country: China
facility: Guanxian People's Hospital
state: Shandong
city: Liaocheng
country: China
facility: The People's Hospital of Gaotang
state: Shandong
city: Linyi
country: China
facility: People's Hospital of Yinan
state: Shandong
city: Tai'an
country: China
facility: The Second Affiliated Hospital of Shandong First Medical University
state: Shandong
city: Weihai
country: China
facility: Weihai Central Hospital
state: Shandong
city: Weihai
country: China
facility: Weihai Wendeng District People's Hospital
state: Shandong
city: Yantai
country: China
facility: Yantai Yuhuangding Hospital
state: Shandong
city: Yantai
country: China
facility: Yantai Taocun Central Hospital
state: Shandong
city: Yantai
country: China
facility: Qixia Traditional Chinese Medicine Hospital
state: Shandong
city: Zibo
country: China
facility: Zibo Central Hospital
state: Shandong
city: Zibo
country: China
facility: Zibo Municipal Hospital
state: Shandong
city: Shanghai
country: China
facility: Shanghai Putuo Liqun Hospital
state: Shanghai
city: Linfen
country: China
facility: Linfen Central Hospital
state: Shanxi
city: Yangquan
country: China
facility: Yangquan Coal Industry(Group) General Hospital
state: Shanxi
city: Yangquan
country: China
facility: Yangquan First People's Hospital
state: Shanxi
city: Nanchong
country: China
facility: Affiliated Hospital of North Sichuan Medical College
state: Sichuan
city: Nanchong
country: China
facility: People's Hospital of Yilong County
state: Sichuan
city: Suining
country: China
facility: Suining Central Hospital
state: Sichuan
city: Tianjin
country: China
facility: Tianjin 4th Center Hospital
state: Tianjin
Study officials:
affiliation: Beijing Tiantan Hospital
name: Yongjun Wang, MD
role: PRINCIPAL_INVESTIGATOR
References: