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

Treatment of Spontaneous Intracerebral Hemorrhage Clinical Trial

— STAPLE-dICH  

Official title:

Safety and Efficacy of Stereotactic Aspiration Plus Urokinase in Deep Intracerebral Hemorrhage Evacuation: a Multicentral Randomized, Controlled, Open-label, Trial

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04686877
• Other study ID #: 2019Y9304
• Status: Recruiting
• Phase: Phase 2/Phase 3
• Start date: September 1, 2020
• Est. completion date: September 30, 2023

Study information

• Verified date: December 2020
• Source: First Affiliated Hospital of Fujian Medical University
• Contact: Lin Fuxin, PHD,MD
• Phone: +86 13552358381
• Email: lfxstuy[@]126.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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 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.

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. This is a multicentral, randomised, controlled, open-label, trial, which will enroll about 500 deep ICH patients in 20 qualified hospitals all over China. The eligible patients should be treated within 24h after bleeding，without cerebral hernia, but with contralateral hemiplegia and GCS≥9. This study is conducted in 2 steps. The first step is a dose climbing test to determine the safety and optimal dose of urokinase irrigation. One hundred patients will be randomly assigned to five groups (20000 U, 40000 U, 60000 U, 80000 U, 10000 U urokinase/2-3 mL saline solution) with a block size of 10 patients. Participants within a block will be assigned equally (2:2:2:2:2) to the five dosage groups. Primary outcomes are safety outcomes: 30-day mortality, 7-day procedure-related mortality, 72 h symptomatic bleeding, and 30-day brain infections. The second step is to validate whether STAPLE ( using the optimal dose determined in step one) is superior to conservative treatment in improving long-term outcomes (1 year) in early (within 24h), non-hernia, contralateral limb hemiplegic dICH patients. Four hundred participants will be randomly allocated by local site personnel using a central web-based interactive response system. Block randomization (size =4) is performed, and participants within a block are assigned equally (2:2) to STAPLE group and Conservative treatment group. Three stratification factors are considered including age (40-64 years versus 65-85 years), initial ICH volume (25-44 ml versus 45-65 ml) and GCS (9-12 scores versus 13-15 scores). Primary outcome is good functional outcome, defined as the proportion ofpatients who achieve a modified Rankin Scale (mRS) score of 0-3 at 1 year after hemorrhage. Analysis of the primary efficacy outcome is performed in the modified intention-to-treat (mITT) population, including all eligible, randomly assigned participants who have been subjected to treatment. Clinical data and radiology data will be collected by electric case report form (CRF) and uploaded online by each neurosurgery center to form the prospective clinical database in First Affiliated Hospital of Fujian Medical University. This RCT study will be across a 3-year period with a 2 years interval of enrollment and 1 year follow up for each patient.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 500
• Est. completion date: September 30, 2023
• Est. primary completion date: August 31, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 14 Years to 75 Years

Eligibility

Inclusion Criteria:

• Patients with a deep spontaneous intracerebral hemorrhage on emergent CT scan (=1 cm from the cortical surface), but without hydrocephalus caused by intraventricular hemorrhage.
• Patients with an age of 14-75 years old and have a mRS of 0-1 before ICH.
• Patients with a clot volume between 25 and 65ml, measured by the ABC/2 method.
• Patients without cerebral herniation and the benefit of surgeical treatment is unknown.
• The time from the ICH attack to the randomization is within 24 hours.
• Patients with motor deficits and the GCS of 9-15.
• Patients with written informed consent, and will accept long-term follow-up.

Exclusion Criteria:

• ICH is caused by aneurysms, arteriovenous malformations, tumor or trauma.
• Patients have a history of intracerebral hemorrhage or ischemic cerebral infarction and are disabled.
• Patients have severe underlying diseases, which may affect the outcomes.
• Patients have severe coagulation disorders with INR = 1.5.
• Pregnant and lactating patients.

Related Conditions & MeSH terms

• Cerebral Hemorrhage
• Hemorrhage
• Treatment of Spontaneous Intracerebral Hemorrhage

Intervention

Procedure:
• STAPLE
Stereotactic aspiration plus urokinase clot irrigation

Locations

Country	Name	City	State
China	First Affiliated Hospital of Fujian Medical University	Fuzhou	Fujian

Sponsors (23)

Lead Sponsor

Collaborator

First Affiliated Hospital of Fujian Medical University

Affiliated Hospital of Putian University, Anxi County Hospital, Department of Science and Technology of Fujian province, Fifth Affiliated Hospital of Zhengzhou University, Fuqing Municipal Hospital, Huian County Hospital, Jinjiang Municipal Hospital, LanZhou University, Lianjiang County Hospital, Longyan City First Hospital, MinDong Hospital of Ningde City, Nanan Hospital, Pucheng County Hospital, Qilu Hospital of Shandong University (Qingdao), Qingyuan People's Hospital, Shaanxi Provincial People's Hospital, Shishi General Hospital, Shunchang County Hospital, Tangshan Gongren Hospital, The Second Hospital of Sanming, The Second Hospital of Shandong University, Wuping County Hospital

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	7-day procedure-related mortality	7-day procedure-related mortality	Within post-operative seventh day
Primary	30-day all-cause mortality	30-day all-cause mortality	Within post-operative thirtith day
Primary	30-day symptomatic re-hemorrhage	30-day symptomatic re-hemorrhage	Within post-operative thirtith day
Primary	30-day brain infections	30-day brain infections	Within post-operative thirtith day