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 the 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.

The LD-IVH study will use a 1:1 stratified block randomization design, with stratification by intraparenchymal hematoma and hospital. Eligible patients will be randomized to receive either (1) control group treatment: standard EVD plus daily intrathecal urokinase (30,000 IU) for 3 consecutive days, with a maximum treatment duration of 5 days; or (2) intervention group treatment: the same EVD and intrathecal urokinase regimen as the control group, with early lumbar drainage additionally initiated within 72 hours of onset. CSF was drained at a rate of ≤8 mL/h, with a daily maximum volume of 200 mL, to keep intracranial pressure stable.

The primary endpoint will be the proportion of patients with a favorable functional outcome (modified Rankin Scale [mRS] score 0-3) at 180 days. A total of 392 patients will be enrolled, and an interim efficacy analysis is planned after 50% of participants complete the 180-day follow-up.

Inclusion criteria

• Aged 18-85 years, of either sex.
• First-ever intracerebral hemorrhage (ICH) with CT-confirmed hemorrhage involving the third and/or fourth ventricle, and scheduled to undergo or already having undergone burr-hole ventricular drainage.
• Intraparenchymal hemorrhage volume <30 mL on admission CT, with stable neurological status and no progressive deterioration before randomization.
• Randomization completed within 72 hours of symptom onset.
• Pre-onset modified Rankin Scale (mRS) score of 0 (no symptoms) or 1 (minor symptoms not interfering with daily activities).
• Written informed consent obtained from the participant or a legal guardian.

Exclusion criteria

• Secondary intracerebral hemorrhage, including imaging-confirmed untreated intracranial arteriovenous malformation (AVM), ruptured intracranial aneurysm, moyamoya disease, or intracranial tumor.
• Long-term use of anticoagulant medication, persistent coagulopathy, or known allergy to urokinase.
• Prothrombin time (PT) or activated partial thromboplastin time (APTT) prolonged to more than twice the upper limit of normal.
• Absolute contraindications to lumbar or external ventricular drainage (e.g., cerebral herniation, infection at the puncture site).
• Infratentorial hemorrhage with a volume ≥10 mL.
• Thalamic hemorrhage with a volume ≥10 mL, or accompanied by obvious extension into the midbrain, oculomotor nerve palsy, or fixed and dilated non-reactive pupils.
• Unilateral limb paralysis (muscle strength grade 0 or 1) before randomization.
• Active bleeding from other sites, including the gastrointestinal, genitourinary, or respiratory tracts.
• Multiple superficial ecchymoses, purpura, or other signs suggesting bleeding or a bleeding tendency.
• Expected survival of less than 6 months due to other causes.
• Other coexisting severe diseases that are difficult to treat.
• Pregnancy.
• Participation in another interventional clinical trial within 30 days before randomization.
• Any other condition that, in the investigator's judgment, makes the participant unsuitable for the study.