Urokinase for Thrombolysis in Acute Ischemic Stroke

Официальное название

A Dose-Escalation Safety Study of Urokinase for Thrombolysis in Patients With Acute Ischemic Stroke

Обзор

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.

Вмешательства

• Препарат Urokinase thrombolysis
  The intravenous thrombolysis group was administered urokinase dissolved in 100 mL of saline via continuous intravenous infusion for 30 min, and the treatment was given within 6 h of stroke onset. The dose escalation plan includes the following increments: 15,000 IU/kg (maximum dose: 1.5 million IU), 20,000 IU/kg (maximum dose: 2.0 million IU), 25,000 IU/kg (maximum dose: 2.5 million IU), and 30,000 IU/kg (maximum dose: 3.0 million IU).

Первичные конечные точки

• Number of participants with major response [Срок оценки: Within 36 hours after intravenous thrombolysis]

Критерии участия

Критерии включения

• 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.

Критерии исключения

• 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 ≥2.
• NIHSS score 1A ≥2.
• 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.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Не применимо

Модель

Одна группа

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Китай · 2 центра

• Xuanwu Hospital, Capital Medical University — Пекин
• Handan Central Hospital — Handan

Публикации

• Wang S, Ma Q, Ji X, Zhao W, Wu L. Urokinase for thrombolysis in patients with acute ischemic stroke: rationale and design of a phase I dose-escalation study. Front Neurol. 2026 Apr 15;17:1750720. doi: 10.3389/fneur.2026.1750720. eCollection 2026. PMID 42064982

Идентификаторы

NCT: NCT07047326 · OUTSET

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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