ProUrokinase in Mild IsChemic strokE (PUMICE)
- Conditions
- MildThrombosisIschemic Stroke
- Interventions
- Drug: Recombinant Human Prourokinase for Injection (rhPro-UK)Drug: standard medical treatment
- Registration Number
- NCT05507645
- Lead Sponsor
- Beijing Tiantan Hospital
- 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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 1446
- Age ≥18 years, any gender;
- Acute ischemic stroke symptom onset within 4.5 hours prior to enrollment; onset time refers to 'last-seen normal time';
- Pre-stroke mRS score≤ 1;
- Baseline NIHSS ≤ 5 (both included);
- Written informed consent from patients or their legally authorized representatives
- Rapidly improving symptoms at the discretion of the investigator;
- Intended to proceed to endovascular treatment during 90 days (including mechanical thrombectomy, stent insertion or balloon expansion);
- Allergy to rhPro-UK and it's components (human albumin, mannitol);
- 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;
- Persistent blood pressure elevation (systolic ≥180 mmHg or diastolic ≥100 mmHg), despite blood pressure lowering treatment;
- Blood glucose <2.8 or >22.2 mmol/L (point of care glucose testing is acceptable);
- 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;
- 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;
- Known defect of platelet function or platelet count below 100,000/mm3 (but patients on antiplatelet agents can be included);
- 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;
- Any terminal illness such that patient would not be expected to survive more than 1 year
- Large cerebral infarction (infarct size > 1/3 MCA territory) on CT or MRI;
- Acute or past intracerebral hemorrhage (ICH) identified by CT or MRI (including intraparenchymal hemorrhage, intraventricular hemorrhage, subarachnoid hemorrhage, subdural/epidural hematoma);
- Pregnant women, nursing mothers, or reluctant to agree taking effective contraceptive measures during the period of trial subjects;
- 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;
- Participation in other interventional clinical trials within the previous 3 months.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description rhPro-UK (35mg) Recombinant Human Prourokinase for Injection (rhPro-UK) rhPro-UK: 35 mg (5 mg per vial, 7 vials in total) Dissolve 15mg (3 vials) of rhPro-UK in 10ml of saline and intravenous bolus within 3 minutes, and dissolve the remaining 20mg (4 vials) in 90ml of saline and intravenous drip within 30 minutes. (Note: after adding saline, overturn it gently once to twice, do not shake vigorously, so as to avoid foaming of the rhPro-UK solution and reduce the efficacy). standard medical treatment standard medical treatment Standard antiplatelet or anticoagulant treatment at the discretion of local investigators according to the 'Chinese guidelines for diagnosis and treatment of acute ischemic stroke 2018'.
- Primary Outcome Measures
Name Time Method The modified Rankin Scale score (mRS) ≤ 1 at 90 days 90 days The proportion of the modified Rankin Scale score (mRS) ≤ 1 at 90 days.
- Secondary Outcome Measures
Name Time Method All-cause death at 90 days 90 days All-cause mortality at 90 days
Ordinal distribution of mRS at 90 days 90 days Ordinal distribution of mRS at 90 days
mRS score ≤ 2 at 90 days 90 days The proportion of mRS score ≤ 2 at 90 days
Early neurological functional improvement 24 hours Clinical response rate at 24 hours defined as an improvement on NIHSS score ≥ 4 points compared with the initial deficit or NIHSS score ≤ 1 point
Barthel index of 75-100 points at 90 days 90 days The proportion of Barthel index of 75-100 points at 90 days
Quality of Life (EQ-5D-5L) at 90 days 90 days The value of Quality of Life (EQ-5D-5L) at 90 days
Activities of Daily Living (Lawton IADL) at 90 days 90 days The score of Activities of Daily Living (Lawton IADL) at 90 days
Adverse events (AEs)/ serious adverse events (SAEs) within 90 days 90 days The proportion of AEs/SAEs within 90 days
Symptomatic intracranial hemorrhage within 36 hours 36 hours The rate of symptomatic intracranial hemorrhage within 36 hours (as defined by ECASS III)
Systematic bleeding at 90 days 90 days The rate of systematic bleeding at 90 days (as defined by GUSTO: moderate and severe bleeding)
Trial Locations
- Locations (89)
Xinji Hospital of T.C.M
🇨🇳Shijiazhuang, Hebei, China
Linxi Hospital of Kailuan General Hospital
🇨🇳Tangshan, Hebei, China
People's Hospital of Huazhou
🇨🇳Maoming, Guangdong, China
Wuchuan People's Hospital
🇨🇳Zhanjiang, Guangdong, China
Wuming Hospital of Guangxi Medical University
🇨🇳Nanning, Guangxi, China
The Second People's Hospital of Guiyang
🇨🇳Guiyang, Guizhou, China
Taihe Hospital of Traditional Chinese Medicine
🇨🇳Fuyang, Anhui, China
Lujiang County People's Hospital,Anhui Province
🇨🇳Hefei, Anhui, China
Beijing Tiantan Hospital, Capital Medical University
🇨🇳Beijing, Beijing, China
The First Hospital of Fangshan District, Beijing
🇨🇳Beijing, Beijing, China
Chongqing Sanbo Chang 'an Hospital
🇨🇳Chongqing, Chongqing, China
Dingxi People's Hospital
🇨🇳Dingxi, Gansu, China
Jiuquan City People's Hospital
🇨🇳Jiuquan, Gansu, China
Guangdong Second Provincial General Hospital
🇨🇳Guangzhou, Guangdong, China
Heyuan People's Hospital
🇨🇳Heyuan, Guangdong, China
The Second Affiliated Hospital of Guizhou Medical University
🇨🇳Kaili, Guizhou, China
The People's Hospital of the Qiandongnan Miao and Dong Autonomous Prefecture
🇨🇳Kaili, Guizhou, China
Affiliated Hospital of Hebei University
🇨🇳Baoding, Hebei, China
Hebei Tang County People Hospital
🇨🇳Baoding, Hebei, China
Chengde Central Hospital
🇨🇳Chengde, Hebei, China
Long Hua Xian Yi Yuan
🇨🇳Chengde, Hebei, China
Fengning Manchu Autonomous County Hospital
🇨🇳Chengde, Hebei, China
Wei Xian Ren Min Yi Yuan
🇨🇳Handan, Hebei, China
The People's Hospital of Changli County
🇨🇳Qinhuangdao, Hebei, China
The Second Hospital of Qinhuangdao
🇨🇳Qinhuangdao, Hebei, China
Xingtang People's Hospital
🇨🇳Shijiazhuang, Hebei, China
Yuanshi Hospital of Traditional Chinese Medicine
🇨🇳Shijiazhuang, Hebei, China
The Second Hospital of Xinji
🇨🇳Shijiazhuang, Hebei, China
Luanzhou People's Hospital
🇨🇳Tangshan, Hebei, China
Tangshan Guye Traditional Chinese Medicine Hospital
🇨🇳Tangshan, Hebei, China
Tangshan Fengnan District Hospital
🇨🇳Tangshan, Hebei, China
Yu Tian Xian Zhong Yi Yi Yuan
🇨🇳Tangshan, Hebei, China
Zunhua People's Hospital
🇨🇳Tangshan, Hebei, China
The People's Hospital of Qianxi County
🇨🇳Tangshan, Hebei, China
Weixian People's Hospital
🇨🇳Xingtai, Hebei, China
The Greatwall Hospital
🇨🇳Xingtai, Hebei, China
Center Hospital·Jiamusi
🇨🇳Jiamusi, Heilongjiang, China
Central Hospital·Jiaozuo
🇨🇳Jiaozuo, Henan, China
The Second People's Hospital of Jiaozuo
🇨🇳Jiaozuo, Henan, China
Jiyuan Hospital of Traditional Chinese Medicine
🇨🇳Jiyuan, Henan, China
Luoyang First People's Hospital
🇨🇳Luoyang, Henan, China
Tanghe County People's Hospital
🇨🇳Nanyang, Henan, China
Puyang Oilfield General Hospital
🇨🇳Puyang, Henan, China
Chinese Medicine Hospital of Puyang
🇨🇳Puyang, Henan, China
The First People Hospital of Lingbao
🇨🇳Sanmenxia, Henan, China
The Shangqiu First People's Hospital
🇨🇳Shangqiu, Henan, China
Xiayi County People's Hospital
🇨🇳Shangqiu, Henan, China
The People's Hospital of Yongcheng
🇨🇳Shangqiu, Henan, China
People's Hospital of Xixian
🇨🇳Xinyang, Henan, China
Guang Shan County People's Hospital
🇨🇳Xinyang, Henan, China
Xinmi Hospital of T.C.M
🇨🇳Zhengzhou, Henan, China
Taikang Xian People's Hospital
🇨🇳Zhoukou, Henan, China
Liuyang Jili Hospital
🇨🇳Changsha, Hunan, China
Baotou City Central Hospital
🇨🇳Baotou, Inner Mongolia, China
Huai'an Second People's Hospital
🇨🇳Huai'an, Jiangsu, China
Funing People's Hospital
🇨🇳Yancheng, Jiangsu, China
Jilin People's Hospital
🇨🇳Jilin, Jilin, China
Tonghua City vascular disease Hospital and Dongchang District People's Hospital
🇨🇳Tonghua, Jilin, China
Meihekou Central Hospital
🇨🇳Tonghua, Jilin, China
Haicheng Hospital of T.C.M
🇨🇳Anshan, Liaoning, China
Dalian Lvshunkou District Traditional Chinese Medicine Hospital
🇨🇳Dalian, Liaoning, China
General Hospital of Fushun Mining Bureau of Liaoning Health Industry Group
🇨🇳Fushun, Liaoning, China
Huludao Center Hospital
🇨🇳Huludao, Liaoning, China
The Second People's Hospital of Huludao
🇨🇳Huludao, Liaoning, China
The Fourth Affiliated Hospital of China Medical University
🇨🇳Shenyang, Liaoning, China
Weinan Central Hospital
🇨🇳Weinan, Shaanxi, China
People's Hospital of Qihe County
🇨🇳Dezhou, Shandong, China
Ningjin People's Hospital
🇨🇳Dezhou, Shandong, China
Liaocheng People's Hospital
🇨🇳Liaocheng, Shandong, China
Liaocheng Third People's Hospital
🇨🇳Liaocheng, Shandong, China
Guanxian People's Hospital
🇨🇳Liaocheng, Shandong, China
The People's Hospital of Gaotang
🇨🇳Liaocheng, Shandong, China
People's Hospital of Yinan
🇨🇳Linyi, Shandong, China
The Second Affiliated Hospital of Shandong First Medical University
🇨🇳Tai'an, Shandong, China
Weihai Central Hospital
🇨🇳Weihai, Shandong, China
Weihai Wendeng District People's Hospital
🇨🇳Weihai, Shandong, China
Yantai Yuhuangding Hospital
🇨🇳Yantai, Shandong, China
Yantai Taocun Central Hospital
🇨🇳Yantai, Shandong, China
Qixia Traditional Chinese Medicine Hospital
🇨🇳Yantai, Shandong, China
Zibo Central Hospital
🇨🇳Zibo, Shandong, China
Zibo Municipal Hospital
🇨🇳Zibo, Shandong, China
Shanghai Putuo Liqun Hospital
🇨🇳Shanghai, Shanghai, China
Linfen Central Hospital
🇨🇳Linfen, Shanxi, China
Yangquan Coal Industry(Group) General Hospital
🇨🇳Yangquan, Shanxi, China
Yangquan First People's Hospital
🇨🇳Yangquan, Shanxi, China
Affiliated Hospital of North Sichuan Medical College
🇨🇳Nanchong, Sichuan, China
People's Hospital of Yilong County
🇨🇳Nanchong, Sichuan, China
Suining Central Hospital
🇨🇳Suining, Sichuan, China
Tianjin 4th Center Hospital
🇨🇳Tianjin, Tianjin, China