Aneurysmal Subarachnoid HemorrhagePhase 4NCT06284642
Early Lumbar Drainage Plus Intrathecal Urokinase in Severe Aneurysmal Subarachnoid Hemorrhage (LD-ITUK)
A Phase 4 study testing Urokinase in people with Aneurysmal Subarachnoid Hemorrhage, run by Second Affiliated Hospital of Nanchang University at 25 sites in China.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Aneurysmal Subarachnoid Hemorrhage
- What is being tested?
- Urokinase
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 424 participants
- Where
- 25 sitesChina
- Study dates
- 28 Mar 2024to 30 Dec 2027
- Phase
- Phase 4
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
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- 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
Trial locations and contacts
25 sites in 1 country. Contact the study team or a site near you to ask about taking part.
25 sites in 1 country
China25 sites, 25 recruiting
- Recruiting
Xiangya Hospital of Central South University
Changsha, Hunan, 410000
Yuchun Zuo, MD
- Recruiting
Sichuan Provincial People's Hospital
Chengdu, Sichuan, 610000
Chunling Li, MD
- Recruiting
The First Affiliated Hospital of Fujian Medical University
Fuzhou, Fujian, 350000
Dengliang Wang, MD
- Recruiting
First Affiliated Hospital of Gannan Medical University
Ganzhou, Jiangxi, 341000
Zhaobin Zhao, MD
- Recruiting
Ganzhou People's Hospital
Ganzhou, Jiangxi, 341000
Zhenyu Zhang, MD
- Recruiting
Zhujiang Hospital of Southern Medical University
Guangzhou, Guangdong, 510000
Xin Feng, MD
- Recruiting
First Affiliated Hospital, Zhejiang University School of Medicine
Hangzhou, Zhejiang, 310000
Kaiyuan Huang, MD
- Recruiting
The Second Affiliated Hospital of Zhejiang University School of Medicine
Hangzhou, Zhejiang, 310000
Xiaoyu Wang, MD
- Recruiting
The First Affiliated Hospital of Harbin Medical University
Harbin, Heilongjiang, 150000
Jingtao Qi, MD
- Recruiting
Anhui Provincial Hospital
Hefei, Anhui, 230000
Yang Wang, MD
- Recruiting
The First Affiliated Hospital of Anhui Medical University
Heihe, Anhui, 230000
Lei Ye, MD
- Recruiting
Qilu hospital of shandong university
Jinan, Shandong, 250000
Ping Zhang, MD
- Recruiting
The First Affiliated Hospital of Shandong First Medical University
Jinan, Shandong, 250000
Chuanjiang Huang, MD
- Recruiting
The Second Affiliated Hospital of Nanchang University
Nanchang, Jiangxi, 330006
Xingen Zhu, MS, zxg2008vip@163.com
- Recruiting
Nanjing Drum Tower Hospital
Nanjing, Jiangsu, 210000
Penglai Zhao, MD
- Recruiting
The first affiliated hospital of nanjing medical university
Nanjing, Jiangsu, 210000
Yifei Wang, MD
- Recruiting
Changhai Hospital, Naval Medical University
Shanghai, Shanghai Municipality, 200000
Rui Zhao, MD
- Recruiting
Huashan hospital of fudan university
Shanghai, Shanghai Municipality, 200000
Dengliang Wang, MD
- Recruiting
Renmin Hospital of Wuhan University
Wuhan, Hubei, 430000
Mingchang Li, MD
- Recruiting
Tongji hospital, Tongji Medical College, Huazhong University of Science and Technology
Wuhan, Hubei, 430000
Hua li, MD
- Recruiting
Union hospital,Tongji Medical College, Huazhong University of Science and Technology
Wuhan, Hubei, 430000
Yin Shen, MD
- Recruiting
Zhongnan Hospital of Wuhan University
Wuhan, Hubei, 430000
Wei Wang, MD
- Recruiting
904th Hospital of Joint Logistic Support Force of PLA
Wuxi, Jiangsu, 214000
Junhui Chen, MD
- Recruiting
Henan Provincial People's Hospital
Zhengzhou, Henan, 450000
Guang Feng, MD
- Recruiting
The First Affiliated Hospital of Zhengzhou University
Zhengzhou, Henan, 450000
Zhiqiang Yao, MD
About this study
Official title: Effectiveness and Safety of Early Lumbar Drainage Plus Intrathecal Urokinase Injection in the Treatment of Severe Aneurysmal Subarachnoid Hemorrhage (LD-ITUK): a Multicentral Randomized Control Trial
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.
Read the 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.
- Conditions
- Aneurysmal Subarachnoid Hemorrhage
- Being tested
- Urokinase, Placebo
- Medical subject headings
- Subarachnoid Hemorrhage
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
UrokinaseDrug
Also called Urokinase-type plasminogen activator
On the basis of standard treatment for severe neurological conditions, within 24 hours of aneurysm treatment, lumbar drainage combined with intrathecal urokinase injection was started. 30,000 IU urokinase dissolved in 3 ml normal saline was injected into the subarachnoid space, 3 ml normal saline was rinsed into the tube, and the tube was clamped for observation for 2 hours, once a day, for 3 consecutive days. Lumbar cisternae drainage Cerebrospinal fluid is slowly and steadily drained at a rate of less than 8ml/h per hour, the daily drainage volume is not more than 200 ml, and the drainage time of lumbar cisternae is controlled within 7 to 10 days, not more than 14 days.
PlaceboDrug
Also called Saline
On the basis of standard treatment for severe neurological conditions, the treatment of lumbar drainage combined with intrathecal placebo saline injection was started within 24 hours after aneurysm treatment, 3 ml placebo was injected into the subarachnoid space, 3 ml normal saline was flushed into the tube, and the tube was observed for 2 hours, once a day for 3 consecutive days. Lumbar cisternae drainage Cerebrospinal fluid is slowly and steadily drained at a rate of less than 8ml/h per hour, the daily drainage volume is not more than 200 ml, and the drainage time of lumbar cisternae is controlled within 7 to 10 days, not more than 14 days.
| Study group | Role | What they receive |
|---|---|---|
| lumbar drainage combined with intrathecal urokinase injection | Active comparator | lumbar drainage combined with intrathecal urokinase injection Receives: Drug: Urokinase |
| lumbar drainage | Placebo comparator | lumbar drainage combined with intrathecal placebo saline injection Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Modified Rankin Scale (mRS)
Good (mRS 0-2) and Poor (mRS 3-6)
Measured: 180 days
Secondary outcomes (13)
Modified Rankin Scale (mRS)
Good (mRS 0-2) and Poor (mRS 3-6)
Measured: 90 days
Relative Modified Rankin Scale (mRS)
Good (mRS 0-3) and Poor (mRS 4-6)
Measured: 90 days, 180 days
Modified Rankin Scale (mRS) distribution
On the distributed proportion in scores (0-6) on the mRS
Measured: 180 days
Glasgow Outcome Scale (GOS）
Good (GOS 4-5) and Poor (GOS 1-3)
Measured: 180 days
Questionnaire EuroQol Five Dimensions Questionnaire (EQ-5D)
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.
Measured: 180 days
Barthel Index for Activities of Daily Living (BI)
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.
Measured: 180 days
Total hospitalized time
Toal hospitalized time from ofter-onset to discharge, including neurocritical care unit
Measured: Discharge (assessed up to 30 days)
Total hospitalized costs
Toal hospitalized costs from ofter-onset to discharge
Measured: Discharge (assessed up to 30 days)
Cerebral vasospasm (CV)
Occurence of any symptomatic or image CV after aSAH
Measured: 14 days
Delayed cerebral ischemia (DCI)
Occurence of any symptomatic or image DCI after aSAH
Measured: 14 days
Death
Occurence of any death during follow-up after operation
Measured: 180 days
Hydrocephalus
Occurence of a hydrocephalus after-onset
Measured: 180 days
Rebleeding
Occurence of a rebleeding after-onset
Measured: 30 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Feb 2024
- Study start28 Mar 2024
- Primary completion30 Jun 2027 (estimated)
- Study completion30 Dec 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Aneurysmal Subarachnoid HemorrhageStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 424 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Second Affiliated Hospital of Nanchang University
- Sponsor type
- University, hospital or other
- Collaborators
- First Affiliated Hospital of Fujian Medical University, Huashan Hospital, Henan Provincial People's Hospital, Tongji Hospital, Southern Medical University, China, Qilu Hospital of Shandong University, Sichuan Provincial People's Hospital, Zhongnan Hospital, Zhejiang University, The First Affiliated Hospital of Zhengzhou University, Xiangya Hospital of Central South University, First Affiliated Hospital of Gannan Medical University, Ganzhou City People's Hospital, The First Affiliated Hospital of Anhui Medical University, Renmin Hospital of Wuhan University, First Affiliated Hospital of Harbin Medical University, The Second Affiliated Hospital of Harbin Medical University, Yichang Central People's Hospital, Xianning Central Hospital, Linyi People's Hospital, Panzhihua Central Hospital, Taizhou Hospital of Zhejiang Province affiliated to Wenzhou Medical University, Changhai Hospital, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School, The First Affiliated Hospital with Nanjing Medical University, 904th Hospital of the Joint Logistics Support Force of the PLA, Qianfoshan Hospital, Dezhou Hospital Qilu Hospital of Shandong University, Liaocheng People's Hospital, Xuanwu Hospital, Beijing, Jiujiang No.1 People's Hospital, The First People's Hospital of Changde City
- Responsible party
- Sponsor
- Investigators
- Xingen Zhu, MS, Principal investigator, Second Affiliated Hospital of Nanchang University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06284642
- Sponsor's protocol ID
- LD-ITUK-2024-001
- Status last verified
- Dec 2025
- First submitted
- 1 Feb 2024
- Last updated
- 5 May 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Wu M, Yan T, Hu P, Wang C, Ye M, Yu Z, Wang Y, Mao G, Xiao B, Gong Y, Li J, Zhao R, Yang P, Liu J, Zhu X; LD-ITUK Investigators. Early lumbar drainage plus intrathecal urokinase in severe aneurysmal subarachnoid hemorrhage: the LD-ITUK randomized controlled trial protocol. Trials. 2026 Apr 13;27(1):379. doi: 10.1186/s13063-026-09716-1.
PubMed 41968344