Weight-adjusted urokinase dosing for early ischemic stroke

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

This research will try different weight-based doses of intravenous urokinase given within 6 hours to find a safe, effective dosing plan for adults with acute ischemic stroke.

Quick facts

• Phase: Not applicable
• Study type: Interventional
• Enrollment: 24 (estimated)
• Ages: 18 Years to 80 Years
• Sex: All
• Sponsor: Capital Medical University (Academic / other)
• Locations: 1 site (Beijing, Beijing Municipality)
• Trial ID: NCT07047326 on ClinicalTrials.gov

What this trial studies

This interventional dose-finding study will administer intravenous urokinase to adults with acute ischemic stroke within 6 hours of symptom onset using a stepwise dose-escalation approach to determine the maximum tolerated dose. Eligible participants (ages 18–80, NIHSS ≥1) without large infarction or intracranial hemorrhage will be closely monitored for bleeding events and clinical outcomes. Data on dose, patient weight, and safety events will be analyzed to derive a standardized weight-adjusted dosing regimen. The study aims to replace currently empirical dosing with evidence-based guidance to improve safety and consistency of urokinase thrombolysis.

Who should consider this trial

Good fit: Adults 18–80 with acute ischemic stroke within 6 hours of a known symptom onset, baseline NIHSS ≥1, no large infarct or intracranial hemorrhage, and able to give consent (or with a guardian who can) are the intended candidates.

Not a fit: Patients with unknown time of onset or beyond 6 hours, large infarct (>1/3 MCA territory), pre-stroke disability (mRS ≥2), active bleeding risk, or existing intracranial hemorrhage are unlikely to benefit from this intervention.

Why it matters

Potential benefit: If successful, patients could receive a standardized weight-based urokinase dose that improves safety and consistency while keeping treatment costs lower than alternatives.

How similar studies have performed: Chinese guideline-based practice and prior reports support intravenous urokinase at 1–1.5 million IU within 6 hours as effective and safe, but weight-adjusted dosing has not been standardized and remains to be tested.

Eligibility criteria

Inclusion Criteria:

1. Age 18-80 years, male or female.
2. Clinical diagnosis as ischemic stroke (the diagnosis following the Chinese Guidelines for the Diagnosis and Treatment of Acute Ischemic Stroke 2023).
3. 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.
4. NIHSS ≥1 at baseline.
5. Subjects or their guardians voluntarily sign the informed consent.

Exclusion Criteria:

1. Head CT or MRI shows a large infarction (infarcted area \>1/3 of the middle cerebral artery).
2. Unknown time of stroke onset.
3. Pre-stroke mRS score ≥2.
4. NIHSS score 1A ≥2.
5. Intracranial hemorrhage (including parenchymal hemorrhage, intraventricular hemorrhage, subarachnoid hemorrhage, subdural/extradural hematoma, etc.).
6. A history of intracranial hemorrhage.
7. Propensity for acute bleeding, including platelet count \<100 × 10⁹/L or otherwise.
8. Having received heparin treatment within 24 h.
9. On oral anticoagulants (e.g., warfarin) with INR \>1.7 or PT \>15s.
10. Patients with planned or prior endovascular therapy.
11. A history of severe head trauma or stroke within 3 months.
12. Intracranial tumors, large intracranial aneurysms.
13. A history of intracranial or spinal surgery within 3 months.
14. A history of major surgery within 2 weeks.
15. Severe liver impairment (e.g., liver failure, cirrhosis, portal hypertension \[esophageal varices\], active hepatitis).
16. A history of gastrointestinal or urinary tract hemorrhage within 3 weeks.
17. Active visceral bleeding.
18. Aortic dissection found.
19. A history of arterial puncture at sites difficult for compression hemostasis within 1 week.
20. Life expectancy \<1 year due to comorbid conditions.
21. 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.
22. Blood glucose \<2.8 mmol/L or \>22.2 mmol/L.
23. Subjects who are unable or unwilling to cooperate due to hemiplegia after epileptic seizure or other neurological/psychiatric disorders.
24. Known to be allergic to urokinase.
25. Bacterial endocarditis, pericarditis, or acute pancreatitis.
26. Participation in other clinical trials within 30 days before screening.
27. Pregnancy, lactating women, or subjects who do not agree to use effective contraception during the trial.
28. Other conditions deemed by the investigator to impair adherence or pose risks to participants.

Where this trial is running

Beijing, Beijing Municipality

• Xuanwu Hospital, Capital Medical University — Beijing, Beijing Municipality, China (Recruiting)

Study contacts

• Study coordinator: Ji Xunming

Conditions Acute Ischemic Stroke; Acute ischemic stroke; Intravenous thrombolysis; Urokinase