Early Lumbar Drainage Plus Intrathecal Urokinase in Severe Aneurysmal Subarachnoid Hemorrhage (LD-ITUK)

NCT06284642 | Recruiting Phase 4 DMC

• 1 other identifier: LD-ITUK-2024-001
• Study Type: interventional
• Target: 424
• Locations: 1 country
• Sites: 25

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.

Conditions

Aneurysmal Subarachnoid Hemorrhage

Outcome Measures

Primary Outcomes (1)

• Modified Rankin Scale (mRS)

  Good (mRS 0-2) and Poor (mRS 3-6)

  180 days

Secondary Outcomes (13)

• Modified Rankin Scale (mRS)

  90 days

• Relative Modified Rankin Scale (mRS)

  90 days, 180 days

• Modified Rankin Scale (mRS) distribution

  180 days

• Glasgow Outcome Scale (GOS）

  180 days

• Questionnaire EuroQol Five Dimensions Questionnaire (EQ-5D)

  180 days

Other Outcomes (3)

• Subarachnoid hemorrhage volume clearance

  30 days

• Correlationship between cerebralspinal fluid pressure with subarachnoid hemorrhage volume

  72 hours after-onset

• Correlationship between clinical grades and subarachnoid hemorrhage volume

  72 hours after-onset

Study Arms (2)

lumbar drainage combined with intrathecal urokinase injection

ACTIVE COMPARATOR

lumbar drainage combined with intrathecal urokinase injection

Drug: Urokinase

lumbar drainage

PLACEBO COMPARATOR

lumbar drainage combined with intrathecal placebo saline injection

Drug: Placebo

Interventions

Urokinase DRUG

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.

Also known as: Urokinase-type plasminogen activator

lumbar drainage combined with intrathecal urokinase injection

Placebo DRUG

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.

Also known as: Saline

lumbar drainage

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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
• Participated in another interventional clinical trial within 30 days before randomization
• Other reasons deemed unsuitable for study participation by the investigator

Sponsors & Collaborators

• Ganzhou City People's Hospital: collaborator
• Panzhihua Central Hospital: collaborator
• The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School: collaborator
• Huashan Hospital: collaborator
• Tongji Hospital: collaborator
• Qilu Hospital of Shandong University: collaborator
• Sichuan Provincial People's Hospital: collaborator
• The First Affiliated Hospital of Zhengzhou University: collaborator
• First Affiliated Hospital of Gannan Medical University: collaborator
• Renmin Hospital of Wuhan University: collaborator
• First Affiliated Hospital of Harbin Medical University: collaborator
• Yichang Central People's Hospital: collaborator
• Xianning Central Hospital: collaborator
• Linyi People's Hospital: collaborator
• The Second Military Medical University Changhai Hospital: collaborator
• Qianfoshan Hospital: collaborator
• Dezhou Hospital Qilu Hospital of Shandong University: collaborator
• Xuanwu Hospital, Beijing: collaborator
• Jiujiang No.1 People's Hospital: collaborator
• The First People's Hospital of Changde City: collaborator
• First Affiliated Hospital of Fujian Medical University: collaborator
• Henan Provincial People's Hospital: collaborator
• Southern Medical University, China: collaborator
• Zhongnan Hospital: collaborator
• Zhejiang University: collaborator
• Xiangya Hospital of Central South University: collaborator
• The First Affiliated Hospital of Anhui Medical University: collaborator
• The Second Affiliated Hospital of Harbin Medical University: collaborator
• Taizhou Hospital of Zhejiang Province affiliated to Wenzhou Medical University: collaborator
• Union Hospital, Tongji Medical College, Huazhong University of Science and Technology: collaborator
• The First Affiliated Hospital with Nanjing Medical University: collaborator
• 904th Hospital of the Joint Logistics Support Force of the PLA: collaborator
• Liaocheng People's Hospital: collaborator
• Second Affiliated Hospital of Nanchang University: lead

Study Sites (25)

Anhui Provincial Hospital

Hefei, Anhui, 230000, China

RECRUITING

The First Affiliated Hospital of Anhui Medical University

Heihe, Anhui, 230000, China

RECRUITING

The First Affiliated Hospital of Fujian Medical University

Fuzhou, Fujian, 350000, China

RECRUITING

Zhujiang Hospital of Southern Medical University

Guangzhou, Guangdong, 510000, China

RECRUITING

The First Affiliated Hospital of Harbin Medical University

Harbin, Heilongjiang, 150000, China

RECRUITING

Henan Provincial People's Hospital

Zhengzhou, Henan, 450000, China

RECRUITING

The First Affiliated Hospital of Zhengzhou University

Zhengzhou, Henan, 450000, China

RECRUITING

Renmin Hospital of Wuhan University

Wuhan, Hubei, 430000, China

RECRUITING

Tongji hospital, Tongji Medical College, Huazhong University of Science and Technology

Wuhan, Hubei, 430000, China

RECRUITING

Union hospital,Tongji Medical College, Huazhong University of Science and Technology

Wuhan, Hubei, 430000, China

RECRUITING

Zhongnan Hospital of Wuhan University

Wuhan, Hubei, 430000, China

RECRUITING

Xiangya Hospital of Central South University

Changsha, Hunan, 410000, China

RECRUITING

Nanjing Drum Tower Hospital

Nanjing, Jiangsu, 210000, China

RECRUITING

The first affiliated hospital of nanjing medical university

Nanjing, Jiangsu, 210000, China

RECRUITING

904th Hospital of Joint Logistic Support Force of PLA

Wuxi, Jiangsu, 214000, China

RECRUITING

First Affiliated Hospital of Gannan Medical University

Ganzhou, Jiangxi, 341000, China

RECRUITING

Ganzhou People's Hospital

Ganzhou, Jiangxi, 341000, China

RECRUITING

The Second Affiliated Hospital of Nanchang University

Nanchang, Jiangxi, 330006, China

RECRUITING

Qilu hospital of shandong university

Jinan, Shandong, 250000, China

RECRUITING

The First Affiliated Hospital of Shandong First Medical University

Jinan, Shandong, 250000, China

RECRUITING

Changhai Hospital, Naval Medical University

Shanghai, Shanghai Municipality, 200000, China

RECRUITING

Huashan hospital of fudan university

Shanghai, Shanghai Municipality, 200000, China

RECRUITING

Sichuan Provincial People's Hospital

Chengdu, Sichuan, 610000, China

RECRUITING

First Affiliated Hospital, Zhejiang University School of Medicine

Hangzhou, Zhejiang, 310000, China

RECRUITING

The Second Affiliated Hospital of Zhejiang University School of Medicine

Hangzhou, Zhejiang, 310000, China

RECRUITING

Related Publications (1)

• 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. doi: 10.1186/s13063-026-09716-1. Online ahead of print.

  PMID: 41968344 DERIVED

MeSH Terms

Conditions

Subarachnoid Hemorrhage

Interventions

Urokinase-Type Plasminogen Activator; Sodium Chloride

Condition Hierarchy (Ancestors)

Intracranial Hemorrhages; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases; Hemorrhage; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Serine Endopeptidases; Endopeptidases; Peptide Hydrolases; Hydrolases; Enzymes; Enzymes and Coenzymes; Serine Proteases; Plasminogen Activators; Blood Coagulation Factors; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Chlorides; Hydrochloric Acid; Chlorine Compounds; Inorganic Chemicals; Sodium Compounds

Study Officials

• Xingen Zhu, MS

  Second Affiliated Hospital of Nanchang University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Xingen Zhu, MS

CONTACT

13803546020; zxg2008vip@163.com

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 1, 2024
• First Posted: February 29, 2024
• Study Start: March 28, 2024
• Primary Completion (Estimated): June 30, 2027
• Study Completion (Estimated): December 30, 2027
• Last Updated: May 5, 2026

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will not share

Locations

CN (25)