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
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- 入组人数
- 1,446
- 试验地点
- 89
- 主要终点
- The modified Rankin Scale score (mRS) ≤ 1 at 90 days
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Single (Outcomes Assessor)
盲法说明
blinded-endpoint
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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.
研究组 & 干预措施
rhPro-UK (35mg)
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).
干预措施: Recombinant Human Prourokinase for Injection (rhPro-UK) (Drug)
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'.
干预措施: standard medical treatment (Drug)
结局指标
主要结局
The modified Rankin Scale score (mRS) ≤ 1 at 90 days
时间窗: 90 days
The proportion of the modified Rankin Scale score (mRS) ≤ 1 at 90 days.
次要结局
- All-cause death at 90 days(90 days)
- Ordinal distribution of mRS at 90 days(90 days)
- mRS score ≤ 2 at 90 days(90 days)
- Early neurological functional improvement(24 hours)
- Barthel index of 75-100 points at 90 days(90 days)
- Quality of Life (EQ-5D-5L) at 90 days(90 days)
- Activities of Daily Living (Lawton IADL) at 90 days(90 days)
- Adverse events (AEs)/ serious adverse events (SAEs) within 90 days(90 days)
- Symptomatic intracranial hemorrhage within 36 hours(36 hours)
- Systematic bleeding at 90 days(90 days)
研究者
Yongjun Wang
professor
Beijing Tiantan Hospital