Early Lumbar Drainage for Intraventricular Hemorrhage

Intraventricular hemorrhage (IVH) is a life-threatening complication of acute stroke, associated with high rates of mortality and severe disability, fewer than 20% of survivors achieve favorable functional outcomes. Despite widespread use of external ventricular drainage (EVD) and intraventricular thrombolysis, the role of early lumbar drainage in improving outcomes remains controversial, with limited high-level evidence from randomized controlled trials.

This study uses a 1:1 stratified block randomization design, with stratification by the etiology of IVH, site of ventricular obstruction, and participating center. Eligible patients will be randomized to receive either:

Control group: Standard treatment with EVD plus daily intrathecal urokinase (30,000 IU) for up to 3 to 5 days.

Intervention group: The same standard EVD and urokinase regimen, plus early lumbar drainage initiated within 24 hours of EVD placement. Drainage will be titrated to a rate ≤8 mL/h, with a maximum daily volume of 200 mL, to maintain stable intracranial pressure.

The primary endpoint is the proportion of patients with a favorable functional outcome (mRS 0-3) at 180 days. Secondary endpoints include 90-day functional status, incidence of post-hemorrhagic hydrocephalus, hospital length of stay, and mortality. Safety endpoints include all-cause mortality, intracranial infection, and cerebral herniation. A total of 392 patients will be enrolled, with an interim efficacy analysis planned when 50% of participants complete their 180-day follow-up.

Inclusion criteria

• Aged 18 to 85 years old, no limitation on gender.
• First-ever intracerebral hemorrhage confirmed by CT/MRI, accompanied by third and/or fourth intraventricular hemorrhage, requiring external ventricular drainage.
• Baseline hemorrhage volume less than 30 mL, with stable clinical condition before randomization.
• External ventricular drainage performed within 48 hours of symptom onset.
• Randomization completed within 24 hours after EVD placement.
• Pre-morbid modified Rankin Scale (mRS) score of 0 or 1.
• Written informed consent obtained from the participant or their legally authorized representative.

Exclusion criteria

• Suspected or untreated ruptured intracranial aneurysm, arteriovenous malformation (AVM), or intracranial tumor, unless excluded by vascular imaging. Previously treated aneurysm or AVM must have been completed at least 3 months prior to enrollment.
• Choroidal vascular malformation or moyamoya disease.

• Long-term oral anticoagulant use, persistent coagulation dysfunction, or known allergy to urokinase.
• Platelet count < 100×10⁹/L or INR > 1.4.
• Absolute contraindications to lumbar cistern drainage or external ventricular drainage, such as cerebral hernia or infection at the puncture site.
• Infratentorial hemorrhage volume ≥ 10 mL.
• Thalamic hemorrhage ≥ 10 mL, or accompanied by midbrain extension, oculomotor nerve palsy, or fixed dilated pupil.
• Hemiplegia with muscle strength grade 0 or 1.
• Active bleeding in the gastrointestinal, genitourinary, or respiratory system.
• Multiple ecchymoses or petechiae suggesting a bleeding tendency.
• Expected survival time less than 6 months.
• Severe, untreatable concomitant systemic diseases.
• Pregnancy.
• Participation in other interventional clinical trials within 30 days prior to randomization.
• Any other condition deemed inappropriate for enrollment by the investigator(s).