Treatment of Spontaneous Intracerebral HemorrhageSTAPLE-dICHNCT04686877
Safety and Efficacy of Stereotactic Aspiration Plus Urokinase in Deep Intracerebral Hemorrhage Evacuation
A study testing STAPLE in people with Treatment of Spontaneous Intracerebral Hemorrhage, run by First Affiliated Hospital of Fujian Medical University at 1 site in China.
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 safety and optimal dose of urokinase intra-hematoma… Read more about this study
- Who is it for?
- Ages 40 years and older
- Conditions the study is for
- Treatment of Spontaneous Intracerebral Hemorrhage
- What is being tested?
- STAPLE
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 400 participants
- Where
- 1 siteChina
- Study dates
- 31 Jan 2021to 30 Sep 2025
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
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 40 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- aged 40 years or older;
- the duration from onset to the baseline computed tomography angiography (CTA) scan was between 6 to 24 hours;
- 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;
- The Glasgow Coma Scale (GCS) ranged from 9 to 15;
- patients with motor deficits;
- The modified Rankin Score (mRS) ranged from 0 to1 before onset.
Who cannot join
- ICH was caused by aneurysms, arteriovenous malformations, tumors, or trauma;
- patients had a history of intracerebral hemorrhage or ischemic cerebral infarction;
- patients had severe coagulation disorders with INR ≥ 1.5;
- patients had severe underlying diseases, which may affect the outcomes;
- pregnant and lactating patients;
- patients refused to sign the informed consent and receive follow-up.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
China1 site, 1 recruiting
- Recruiting
First Affiliated Hospital of Fujian Medical University
Fuzhou, Fujian
Lin Fuxin, MD, +86 13552358381, lfxstudy@126.com
Kang Dezhi, PHD,MD
About this study
Official title: Safety and Efficacy of Stereotactic Aspiration Plus Urokinase in Deep Intracerebral Hemorrhage Evacuation: a Multicentral Randomized, Controlled, Open-label, Trial
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.
Read the 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.
- Being tested
- STAPLE
- Keywords
- Deep-Seated Spontaneous Intracerebral Hemorrhage, Stereotactic Aspiration, Urokinase Irrigation, Randomized Controlled Trial, Long-term outcome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
STAPLEProcedure or surgery
Stereotactic aspiration plus urokinase clot irrigation
| Study group | Role | What they receive |
|---|---|---|
| STAPLE group | Experimental | 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. Receives: Procedure: STAPLE |
| Conservative treatment group | No intervention | 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. |
What is being measured
The primary outcome is the main question the study is designed to answer.
Good functional outcome, measured by the modified Rankin Scale (mRS)
Good functional outcome is defined as a mRS of ≤3 points and will be assessed as binary outcome (yes/no, final value). In this context, a mRS score of 3 points reflects the ability to walk unassisted and care for one's own bodily needs despite being moderately dependent on assistance, while a mRS score of 4 points describes a patient who is not able to walk anymore and needs assistance with all daily activities and thus marks a severe loss of patient autonomy.
Measured: At day 365 after randomization
Secondary outcomes (3)
Proportion of hematoma evacuation by craniotomy or decompressive hemicraniectomy
Number of participants who were converted to hematoma evacuation by craniotomy or decompressive hemicraniectomy for reasons such as hematoma enlargement after conservative treatment or urokinase treatment.
Measured: at 1 year after randomization
Residual hematoma volume
Proportion of patients with hematoma volume reduced to less than 10mL [binary outcome (yes/no)]. The hematoma volume will be measured on cranial computer tomography (cCT) at day 7 after randomization in the Conservative Treatment group and 72 hours after the last urokinase infusion in the STAPLE group.
Measured: At day 7 after randomization in the Conservative Treatment group; At 72 hours after the last urokinase infusion in the STAPLE group
All-cause mortality
Mortality rate as measured by death of a participant [binary outcome (yes/no)]. Death induced by any cause.
Measured: At 365 days after randomization
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Dec 2020
- Study start31 Jan 2021
- Primary completion31 Aug 2025 (estimated)
- Study completion30 Sep 2025 (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 Treatment of Spontaneous Intracerebral HemorrhageStudies of the same condition, open and under way.
- More trials run by First Affiliated Hospital of Fujian Medical UniversityThe sponsor's other registered studies.
- 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 N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- A surgical intervention model of stereotactic hematoma punctural catheter placement, drainage and urokinase irrigation in spontaneous intracerebral hemorrhage.
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 400 participants (estimated)
Sponsor and investigators
- Sponsor type
- University, hospital or other
- Collaborators
- Department of Science and Technology of Fujian province, Longyan City First Hospital, The First Affiliated Hospital of Zhengzhou University, Shanxi Provincial People's Hospital, Tangshan Gongren Hospital, Lanzhou University Second Hospital, Qilu Hospital of Shandong University (Qingdao), The Second Hospital of Shandong University, Shishi General Hospital, Wuping County Hospital, Fuqing Municipal Hospital, Qingyuan People's Hospital, Jinjiang Municipal Hospital, Anxi County Hospital, Nanan Hospital, MinDong Hospital of Ningde City, The Affiliated Hospital of Putian University, Lianjiang County Hospital, Shunchang County Hospital, Yulin No.2 Hospital, The First Affiliated Hospital of Xiamen University, Second Affiliated Hospital of Xiamen Medical College, Zhangzhou Municipal Hospital of Fujian Province, Longyan People's Hospital of Fujian Province
- Responsible party
- Principal investigator, De-zhi Kang, First Affiliated Hospital of Fujian Medical University
- Investigators
- Kang Dezhi, MD., Study chair, The first affilicated hospital of Fujian Medical univercity
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04686877
- Sponsor's protocol ID
- 2019Y9118
- Acronym
- STAPLE-dICH
- Status last verified
- Feb 2025
- First submitted
- 23 Dec 2020
- Last updated
- 12 Feb 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: We will share individual participant data after the primary results have been published.
Publications
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.
PubMed 39227662
Study at a glance
From the registry record, last updated by the sponsor on 12 Feb 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Safety and Efficacy of Stereotactic Aspiration Plus Urokinase in Deep Intracerebral Hemorrhage Evacuation: a Multicentral Randomized, Controlled, Open-label, Trial
- ClinicalTrials.gov ID
- NCT04686877
- Acronym / sponsor ID
- STAPLE-dICH / 2019Y9118
- Keywords
- Deep-Seated Spontaneous Intracerebral Hemorrhage, Stereotactic Aspiration, Urokinase Irrigation, Randomized Controlled Trial, Long-term outcome
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 400 participants (estimated)
- Lead sponsor
- First Affiliated Hospital of Fujian Medical UniversityUniversity, hospital or other
- Collaborators
- Department of Science and Technology of Fujian province, Longyan City First Hospital, The First Affiliated Hospital of Zhengzhou University, Shanxi Provincial People's Hospital, Tangshan Gongren Hospital, Lanzhou University Second Hospital, Qilu Hospital of Shandong University (Qingdao), The Second Hospital of Shandong University, Shishi General Hospital, Wuping County Hospital, Fuqing Municipal Hospital, Qingyuan People's Hospital, Jinjiang Municipal Hospital, Anxi County Hospital, Nanan Hospital, MinDong Hospital of Ningde City, The Affiliated Hospital of Putian University, Lianjiang County Hospital, Shunchang County Hospital, Yulin No.2 Hospital, The First Affiliated Hospital of Xiamen University, Second Affiliated Hospital of Xiamen Medical College, Zhangzhou Municipal Hospital of Fujian Province, Longyan People's Hospital of Fujian Province
- Study start
- 31 Jan 2021 (actual)
- Primary completion
- 31 Aug 2025 (estimated)
- Study completion
- 30 Sep 2025 (estimated)
- First posted
- 29 Dec 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (outcomes assessor)
- Number of arms
- 2
- Model description
- A surgical intervention model of stereotactic hematoma punctural catheter placement, drainage and urokinase irrigation in spontaneous intracerebral hemorrhage.
| Arm | Type | Receives |
|---|---|---|
| STAPLE group | Experimental | Procedure: STAPLEIn 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. |
| Conservative treatment group | No intervention | –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. |
Who may qualify
- Ages
- 40 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- aged 40 years or older;
- the duration from onset to the baseline computed tomography angiography (CTA) scan was between 6 to 24 hours;
- 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;
- The Glasgow Coma Scale (GCS) ranged from 9 to 15;
- patients with motor deficits;
Key exclusion criteria (6 listed)
- ICH was caused by aneurysms, arteriovenous malformations, tumors, or trauma;
- patients had a history of intracerebral hemorrhage or ischemic cerebral infarction;
- patients had severe coagulation disorders with INR ≥ 1.5;
- patients had severe underlying diseases, which may affect the outcomes;
- pregnant and lactating patients;
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| STAPLEStereotactic aspiration plus urokinase clot irrigation | Procedure or surgery | STAPLE group |
Primary outcome
Good functional outcome, measured by the modified Rankin Scale (mRS)
Time frame: At day 365 after randomization
Good functional outcome is defined as a mRS of ≤3 points and will be assessed as binary outcome (yes/no, final value). In this context, a mRS score of 3 points reflects the ability to walk unassisted and care for one's own bodily needs despite being moderately dependent on assistance, while a mRS score of 4 points describes a patient who is not able to walk anymore and needs assistance with all daily activities and thus marks a severe loss of patient autonomy.
3 secondary outcomes
Proportion of hematoma evacuation by craniotomy or decompressive hemicraniectomy
Time frame: at 1 year after randomization
Residual hematoma volume
Time frame: At day 7 after randomization in the Conservative Treatment group; At 72 hours after the last urokinase infusion in the STAPLE group
All-cause mortality
Time frame: At 365 days after randomization
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Feb 2025.
- Derived from this study: PubMed 39227662Yan 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.
- Individual participant dataSharing planned: No. We will share individual participant data after the primary results have been published.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Kang Dezhi, MD. study chair
The first affilicated hospital of Fujian Medical univercity
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing STAPLE in people with Treatment of Spontaneous Intracerebral Hemorrhage, run by First Affiliated Hospital of Fujian Medical University at 1 site in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 12 Feb 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Lin Fuxin, PHD,MD (+86 13552358381, lfxstuy@126.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Good functional outcome, measured by the modified Rankin Scale (mRS) (time frame: At day 365 after randomization). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04686877, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 12 Feb 2025.