Early Lumbar Drainage for Intraventricular Hemorrhage

Официальное название

Effectiveness and Safety of Early Lumbar Drainage in the Treatment of Ventricular Hemorrhage: the LD-IVH Randomized Controlled Trial

Обзор

This is a multicenter, prospective, randomized, open-label, blinded-endpoint (PROBE) trial comparing the addition of early lumbar drainage to standard care in patients with intraventricular hemorrhage (IVH) in China. The primary objective is to evaluate whether early lumbar drainage improves long-term functional outcomes at 180 days, as measured by the modified Rankin Scale (mRS), and reduces complications in patients treated with external ventricular drainage (EVD) and intrathecal urokinase.

Подробное описание

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.

Вмешательства

• Процедура Lumbar Drainage combined with external ventricular drainage plus Intrathecal Urokinase
  Early lumbar cistern drainage is performed within 24 hours. CSF drainage speed is controlled below 8 mL/h, and daily total drainage volume does not exceed 200 mL to maintain stable intracranial pressure.
• Процедура External ventricular drainage plus Intrathecal Urokinase
  Patients receive external ventricular drainage combined with intrathecal urokinase injection. Single dose 30,000 IU per day for continuous 3 days; the maximum duration of urokinase treatment shall not exceed 5 days. Discontinue medication when third/fourth ventricular clot clearance, relieved mass effect, or hematoma clearance rate ≥80% on cranial CT.

Первичные конечные точки

• Proportion of participants with mRS score 0-3 at 180 days after onset [Срок оценки: 180 days after disease onset]

Вторичные конечные точки (9)

• Proportion of participants with mRS 0-3 at 90 days after onset [Срок оценки: 90 days after onset]
• Proportion of participants with GOS score 4-5 at 180 days after onset [Срок оценки: 180 days after onset]
• Proportion of participants with mRS 0-2 at 90 days and 180 days [Срок оценки: 90 days, 180 days after onset]
• Ordinal change of mRS score from baseline to 180 days [Срок оценки: Baseline to 180 days]
• EQ-5D health utility score at 180 days [Срок оценки: 180 days after onset]
• Proportion of participants with Barthel index 75-100 at 180 days [Срок оценки: 180 days after onset]
• Incidence of post-hemorrhagic hydrocephalus [Срок оценки: Up to 180 days after onset]
• Length of hospital stay [Срок оценки: Perioperative period]
• Total hospitalization cost [Срок оценки: Perioperative period]

Критерии участия

Критерии включения

• 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.

Критерии исключения

• 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).

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

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Китай · 29 центров

• Fuzhou First People's Hospital — Фучжоу
• Changde First People's Hospital — Changde
• Lingcheng District People's Hospital — Dezhou
• Qilu Hospital of Shandong University Dezhou Hospital — Dezhou
• Ganzhou People's Hospital — Ganzhou
• Ruijin People's Hospital — Ganzhou
• The First Affiliated Hospital of Gannan Medical University — Ganzhou
• The Affiliated Hospital of Guizhou Medical University — Guiyang
• … и ещё 21 центр

Идентификаторы

NCT: NCT07625449 · LD-IVH-2026-001 · ChiCTR2600123877

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)
• ChiCTR ChiCTR2600123877 (Китайский реестр КИ)

Открыть это исследование на ClinicalTrials.gov ↗