Early Lumbar Drainage Combined With Intrathecal Urokinase Injection for Treatment of Severe Aneurysmal SAH (LD-ITUK)
- Conditions
- Aneurysmal Subarachnoid Hemorrhage
- Interventions
- Drug: Placebo
- Registration Number
- NCT06284642
- Lead Sponsor
- Second Affiliated Hospital of Nanchang University
- Brief Summary
The LD-ITUK is a multicenter, prospective, randomized, double-blind, blind endpoint, placebo-control design trial. All eligible patients with the diagnosis of severe aSAH will be randomly assigned to the treatment group or the placebo group. Patients in the treatment group will receive standard treatment with the addition of lumbar drainage combined with intrathecal urokinase injection started within 24 hours after aneurysm treatment with 30000 IU urokinase, once a day for 3 consecutive days. Patients in the control group will receive standard treatment with the addition of lumbar drainage combined with intrathecal placebo (0.9%NaCl) injection. The primary outcome measure is favorable functional outcome, defined as a score of 0 to 2 on the modified Rankin Scale (mRS), at 6 months after aneurysmal SAH. Primary outcome will be determined by a member of the Independent Committee on Terminal events.
- Detailed Description
Aneurysmal subarachnoid hemorrhages (aSAH) represent about 8% of all strokes and 9.8 per 100,000 per year in China, which is higher than the overall annual incidence rate worldwide. The cumulative death rate after-onset represent about 24.6% in China, only about 30% survivors will be able to have a good neurological prognosis, the majority of the remaining survivors suffer from long-term disability or cognitive impairment. However, these condition may be even worse in patients with severe aSAH.
Studies suggest that early clearance of subarachnoid clot may be associated with a good neurological prognosis. Indeed, subarachnoid clot aggravate the phenomena of cerebral vasospasm and delayed cerebral ischemia in the delayed phase, and promote cell injure within the hypoperfusion zone of the brain in the longer term. Thus, early removal of subarachnoid clot may have a favorable effect on neurological prognosis. Current aSAH recommendations and guidelines advocate the use of lumbar drainage only in case of acute hydrocephalus. The EARLYDRAIN trial suggests that lumber cerebrospinal fluid drainage can early remove subarachnoid clot compare to the standard neurocritical treatment, and improve the prognosis after aSAH. However, the ratio of unfavorable prognosis in severe aSAH is still high.
Intrathecal urokinase injection has been proved to effeciently remove the subarachnoid clot, however, no randomized control trials have been conducted to evaluate the improvement of lumbar drainage combined with intrathecal urokinase injection in the favorable functional outcome, defined as a score of 0 to 2 on the modified Rankin Scale (mRS), at 6 months after aneurysmal SAH.
The LD-ITUK trial was designed to evaluate whether severe aSAH treated by standard treatment with the addition of lumbar drainage combined with intrathecal urokinase injection have a significantly higher percentage of favourable outcome after six months (score 0-2 on the Modified Rankin Scale) compared to the placebo treated by standard treatment with the addition of lumbar drainage combined with intrathecal placebo (0.9%NaCl) injection.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 424
- Patient's age ≥ 18 years
- First occurrence of aneurysmal subarachnoid hemorrhage
- Patients without any craniotomy treatment before onset
- Hunt-Hess grade III-V
- mRS grade 0 or 1 before onset
- Aneurysm treatment within 48 hours of onset
- Informed consent given by the subject or guardian
- Subarachnoid hemorrhage caused by arteriovenous malformation or moyamoya disease or other cerebrovascular disease
- Patients requiring craniotomy to remove intracranial hematoma
- modified Fisher Scale grade 0
- Prothrombin time (PT) and activated partial thromboplastin time (APTT) are greater than 2 times the extended range
- Absolute contraindications for lumbar puncture (e.g., brain hernia, puncture site infection)
- Patients with a life expectancy of less than 1 year due to other causes
- Other concomitant serious diseases that are difficult to treat;
- Pregnant woman
- Patients who were known to be allergic to urokinase and excipients or had a history of severe allergy and were deemed unsuitable for inclusion by the investigators
- Participated in another interventional clinical trial within 30 days before randomization
- Other reasons deemed unsuitable for study participation by the investigator
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description lumbar drainage Placebo lumbar drainage combined with intrathecal placebo saline injection lumbar drainage combined with intrathecal urokinase injection Urokinase lumbar drainage combined with intrathecal urokinase injection
- Primary Outcome Measures
Name Time Method Modified Rankin Scale (mRS) 180 days Good (mRS 0-2) and Poor (mRS 3-6)
- Secondary Outcome Measures
Name Time Method Modified Rankin Scale (mRS) distribution 180 days On the distributed proportion in scores (0-6) on the mRS
Questionnaire EuroQol Five Dimensions Questionnaire (EQ-5D) 180 days EQ-5D questionnaires have 5 dimensions: "Mobility", "Human Autonomy," "Current Activities", "Pain / Discomfort", "Anxiety / Depression" and all dimensions are described by 3 problem levels corresponding to patient response choices.
Barthel Index for Activities of Daily Living (BI) 180 days The Barthel Index (BI) measures the extent to which somebody can function independently and has mobility in their activities of daily living (ADL) i.e. feeding, bathing, grooming, dressing, bowel control, bladder control, toileting, chair transfer, ambulation and stair climbing.
Total hospitalized time Discharge (assessed up to 30 days) Toal hospitalized time from ofter-onset to discharge, including neurocritical care unit
Modified Rankin Scale (mRS) 90 days Good (mRS 0-2) and Poor (mRS 3-6)
Relative Modified Rankin Scale (mRS) 90 days, 180 days Good (mRS 0-3) and Poor (mRS 4-6)
Total hospitalized costs Discharge (assessed up to 30 days) Toal hospitalized costs from ofter-onset to discharge
Hydrocephalus 180 days Occurence of a hydrocephalus after-onset
Glasgow Outcome Scale (GOS） 180 days Good (GOS 4-5) and Poor (GOS 1-3)
Rebleeding 30 days Occurence of a rebleeding after-onset
Death 180 days Occurence of any death during follow-up after operation
Cerebral vasospasm (CV) 14 days Occurence of any symptomatic or image CV after aSAH
Delayed cerebral ischemia (DCI) 14 days Occurence of any symptomatic or image DCI after aSAH
Trial Locations
- Locations (1)
The Second Affiliated Hospital of Nanchang University
🇨🇳Nanchang, Jiangxi, China