A Dose-Escalation Safety Study of Urokinase for Thrombolysis in Patients With Acute Ischemic Stroke
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 发起方
- 入组人数
- 24
- 试验地点
- 2
- 主要终点
- Number of participants with major response
研究概览
简要总结
According to the Chinese Guidelines for the Diagnosis and Treatment of Ischemic Stroke, intravenous thrombolysis with urokinase, administered at doses of 1-1.5 million IU within 6 hours of symptom onset, has been shown to be both safe and effective for patients with acute ischemic stroke. Compared to alteplase, urokinase offers considerable cost advantages while maintaining comparable therapeutic efficacy. However, current dosing protocols in clinical practice largely rely on the empirical judgment of physicians rather than evidence-based standardization. Therefore, the development of a weight-adjusted dosing regimen for urokinase is of significant clinical importance in optimizing treatment outcomes and ensuring patient safety. The purpose of this study is to determine the maximum tolerated dose of urokinase thrombolytic treatment in patients with acute ischemic stroke and to develop an optimal weight-adjusted dosing regimen.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age 18-80 years, male or female.
- •Clinical diagnosis as ischemic stroke (the diagnosis following the Chinese Guidelines for the Diagnosis and Treatment of Acute Ischemic Stroke 2023).
- •Time from onset to treatment <6h; the time of symptom onset is defined as "the last time point at which the patient appears normal", and the symptoms of stroke persist for at least 30 minutes and show no significant improvement before treatment.
- •NIHSS ≥1 at baseline.
- •Subjects or their guardians voluntarily sign the informed consent.
排除标准
- •Head CT or MRI shows a large infarction (infarcted area >1/3 of the middle cerebral artery).
- •Unknown time of stroke onset.
- •Pre-stroke mRS score ≥
- •NIHSS score 1A ≥
- •Intracranial hemorrhage (including parenchymal hemorrhage, intraventricular hemorrhage, subarachnoid hemorrhage, subdural/extradural hematoma, etc.).
- •A history of intracranial hemorrhage.
- •Propensity for acute bleeding, including platelet count <100 × 10⁹/L or otherwise.
- •Having received heparin treatment within 24 h.
- •On oral anticoagulants (e.g., warfarin) with INR >1.7 or PT >15s.
- •Patients with planned or prior endovascular therapy.
- •A history of severe head trauma or stroke within 3 months.
- •Intracranial tumors, large intracranial aneurysms.
- •A history of intracranial or spinal surgery within 3 months.
- •A history of major surgery within 2 weeks.
- •Severe liver impairment (e.g., liver failure, cirrhosis, portal hypertension [esophageal varices], active hepatitis).
- •A history of gastrointestinal or urinary tract hemorrhage within 3 weeks.
- •Active visceral bleeding.
- •Aortic dissection found.
- •A history of arterial puncture at sites difficult for compression hemostasis within 1 week.
- •Life expectancy <1 year due to comorbid conditions.
- •Uncontrollable hypertension upon active antihypertensive treatment: systolic blood pressure ≥180 mm Hg, or diastolic blood pressure ≥100 mm Hg on ≥3 repeated measurements at 10-minute intervals.
- •Blood glucose <2.8 mmol/L or >22.2 mmol/L.
- •Subjects who are unable or unwilling to cooperate due to hemiplegia after epileptic seizure or other neurological/psychiatric disorders.
- •Known to be allergic to urokinase.
- •Bacterial endocarditis, pericarditis, or acute pancreatitis.
- •Participation in other clinical trials within 30 days before screening.
- •Pregnancy, lactating women, or subjects who do not agree to use effective contraception during the trial.
- •Other conditions deemed by the investigator to impair adherence or pose risks to participants.
研究组 & 干预措施
Intravenous urokinase group
The safety and tolerability of urokinase will be investigated using a rolling six-dose escalation trial design.
干预措施: Urokinase thrombolysis (Drug)
结局指标
主要结局
Number of participants with major response
时间窗: Within 36 hours after intravenous thrombolysis
Major response is any of the following: 1. Symptomatic intracranial hemorrhage; 2. Parenchymal hemorrhage type 2; 3. Any intracranial hemorrhage; 4. Major bleeding and clinically relevant non-major bleeding.
次要结局
未报告次要终点
研究者
Ji Xunming,MD,PhD
Professor
Capital Medical University