Safety and Efficacy of Stereotactic Aspiration Plus Urokinase in Deep Intracerebral Hemorrhage Evacuation

NCT ID: NCT04686877

Last Updated: 2025-02-12

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: NA
• Total Enrollment: 400 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-01-31
• Study Completion Date: 2025-09-30

Brief Summary

This is a nationwide, multicenter, open-label, randomized controlled trial of early minimally invasive treatment for deep-seated spontaneous cerebral hemorrhage (dICH). The study consists of 2 steps: the first step is to conduct a dose climbing test to determine the safety and optimal dose of urokinase intra-hematoma irrigation after stereotactic aspiration; the second step is to validate whether stereotactic aspiration plus urokinase irrigation (the optimal dose determined in step one) is superior to conservative treatment in improving long-term outcomes (1 year) in early (within 24h) dICH patients.

Detailed Description

Surgical options have been repeatedly evaluated in large multicenter randomized controlled trials that unfortunately have not demonstrated improved outcomes. Recently, MISTIE III study concluded that minimally invasive surgery with thrombolysis was safely adopted by doctors, but did not improve the proportion of patients who achieved a good long-term outcome. However, subgroup analyses of MISTIE cohorts showed that patients with GCS≥9, time from stroke to treatment initiation <36 h, and reduction of ICH to ≤15 mL had a higher likelihood of achieving mRS of 0 to 3. Thus, we designed this study, considering the reality of clinical practice in China and the limitations of previous studies, to determine the optimal dose and safety of urokinase intra-hematoma irrigation, and to validate whether stereotactic aspiration plus urokinase irrigation (STAPLE) is superior to conservative treatment in improving long-term outcomes (1 year) in early (within 24h) dICH patients.

The Part A study aimed to find the safe optimal dose of urokinase by a Utility-based Bayesian optimal interval (U-BOIN) phase I/II design. In this design, the dose-limiting toxicity (DLT) is defined as rebleeding that occurred from the first urokinase injection to 72 h after the last injection. And the effective performance is defined as a hematoma volume <10 ml on CT scan after the last injection as well as the total number of injections not exceeding four. he demographic data, medical history, examination results, complications, treatment, and survival information of the participants are recorded during hospitalization. The participants should go to the outpatient clinic on the 30th day after entering the study, and their CT scan and neurological examination results will be recorded. If the participants died, the time and cause of death will be collected. In the Part B study, eligible patients will be randomized in equal proportions between STAPLE group and conservative treatment group immediately after the pre-surgical CTA. The method of block randomization and stratification control is used. Patients in the STAPLE group receive the stereotactic CTA-guided aspiration and drainage within 36h after symptoms onset, and the injection volume of urokinase was determined according to the results of CT examination at 6 hours after operation. Patients in the conservative treatment group are treated routinely according to the Guidelines for the Management of Spontaneous Intracerebral Hemorrhage (AHA/ASA, 2015). Hematoma evacuation by craniotomy or decompressive hemicraniectomy is considered in deteriorating patients as a life-saving measure. Subjects will be followed up by phone at days 90, 180, and 270. And the survivors should go to the outpatient clinic of the participating centers at day 30 and day 365 after randomization. Their CT results and neurological physical examination (including but not limited to mRS, Glasgow Outcome Score (GOS), and Barthel Index (BI)) will be recorded.

Conditions

Treatment of Spontaneous Intracerebral Hemorrhage

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: SINGLE

Study Groups

STAPLE group

In patients enrolled in the STAPLE group to receive the stereotactic CTA-guided aspiration and drainage, the surgery is performed within 36 h of symptoms onset. Urokinase injection is determined according to the CT scan 6 h after the surgery. Then the optimal dose of urokinase determined in Step A will be given. On the 1st, 3rd, 5th, and 7th day of post-operation, patients will be re-examined using CT. Conventional craniotomy and hematoma evacuation can be performed when cerebral hernia or rebleeding happened.

Group Type: EXPERIMENTAL

STAPLE

Intervention Type: PROCEDURE

Stereotactic aspiration plus urokinase clot irrigation

Conservative treatment group

Patients in the conservative treatment group are treated routinely in accordance with Guidelines for the Management of Spontaneous Intracerebral Hemorrhage (AHA/ASA, 2015) 9. Hematoma evacuation by craniotomy or decompressive hemicraniectomy is considered in deteriorating patients as a life-saving measure.

Group Type: NO_INTERVENTION

No interventions assigned to this group

Interventions

STAPLE

Stereotactic aspiration plus urokinase clot irrigation

Intervention Type: PROCEDURE

Eligibility Criteria

Inclusion Criteria

1. aged 40 years or older;

2. the duration from onset to the baseline computed tomography angiography (CTA) scan was between 6 to 24 hours;

3. patients with a spontaneous ICH in the deep brain parenchyma (≥1 cm from the cortical surface); with hematoma volume more than 25 ml (measured with the ABC/2 method); without hydrocephalus caused by intraventricular hemorrhage; without cerebral herniation and the benefit of surgical treatment was unknown;

4. The Glasgow Coma Scale (GCS) ranged from 9 to 15;

5. patients with motor deficits;

6. The modified Rankin Score (mRS) ranged from 0 to1 before onset.

Exclusion Criteria

1. ICH was caused by aneurysms, arteriovenous malformations, tumors, or trauma;

2. patients had a history of intracerebral hemorrhage or ischemic cerebral infarction;

3. patients had severe coagulation disorders with INR ≥ 1.5;

4. patients had severe underlying diseases, which may affect the outcomes;

5. pregnant and lactating patients;

6. patients refused to sign the informed consent and receive follow-up.

• Minimum Eligible Age: 40 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Department of Science and Technology of Fujian province

UNKNOWN

Sponsor Role: collaborator

Longyan City First Hospital

OTHER

Sponsor Role: collaborator

Fifth Affiliated Hospital of Zhengzhou University

UNKNOWN

Sponsor Role: collaborator

Shanxi Provincial People's Hospital

OTHER_GOV

Sponsor Role: collaborator

Tangshan Gongren Hospital

OTHER

Sponsor Role: collaborator

Lanzhou University Second Hospital

OTHER

Sponsor Role: collaborator

Qilu Hospital of Shandong University (Qingdao)

OTHER

Sponsor Role: collaborator

The Second Hospital of Shandong University

OTHER

Sponsor Role: collaborator

Shishi General Hospital

UNKNOWN

Sponsor Role: collaborator

Wuping County Hospital

UNKNOWN

Sponsor Role: collaborator

Fuqing Municipal Hospital

UNKNOWN

Sponsor Role: collaborator

Qingyuan People's Hospital

OTHER

Sponsor Role: collaborator

Jinjiang Municipal Hospital

UNKNOWN

Sponsor Role: collaborator

Anxi County Hospital

UNKNOWN

Sponsor Role: collaborator

Nanan Hospital

UNKNOWN

Sponsor Role: collaborator

MinDong Hospital of Ningde City

UNKNOWN

Sponsor Role: collaborator

Affiliated Hospital of Putian University

UNKNOWN

Sponsor Role: collaborator

Lianjiang County Hospital

UNKNOWN

Sponsor Role: collaborator

Shunchang County Hospital

UNKNOWN

Sponsor Role: collaborator

Yulin No.2 Hospital

OTHER

Sponsor Role: collaborator

The First Affiliated Hospital of Xiamen University

OTHER

Sponsor Role: collaborator

The Second Affiliated Hospital of Xiamen Medical College

UNKNOWN

Sponsor Role: collaborator

Zhangzhou Municipal Hospital of Fujian Province

OTHER

Sponsor Role: collaborator

Longyan People's Hospital of Fujian Province

UNKNOWN

Sponsor Role: collaborator

First Affiliated Hospital of Fujian Medical University

OTHER

Sponsor Role: lead

Responsible Party

De-zhi Kang

Doctor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Kang Dezhi, MD.

Role: STUDY_CHAIR

The first affilicated hospital of Fujian Medical univercity

Locations

First Affiliated Hospital of Fujian Medical University

Fuzhou, Fujian, China

Site Status: RECRUITING

Countries

China

Central Contacts

Lin Fuxin, PHD,MD

Role: CONTACT

lfxstuy@126.com

+86 13552358381

Kang Dezhi, MD

Role: CONTACT

kdz999888@163.com

+86 13859099988

Facility Contacts

Lin Fuxin, MD

Role: primary

lfxstudy@126.com

+86 13552358381

References

Yan Z, Jiang L, Li G, Xia K, Peng L, Hu J, Chen S, Zhang J, Huang X. Efficacy study of neuronavigation-assisted stereotactic drilling of urokinase drainage versus craniotomy in the treatment of massive intracerebral haemorrhage in elderly patientsa. Sci Rep. 2024 Sep 3;14(1):20439. doi: 10.1038/s41598-024-71130-x.

Reference Type: DERIVED

PMID: 39227662 (View on PubMed)

Other Identifiers

2019Y9118

Identifier Type: -

Identifier Source: org_study_id