An interventional study of STAPLE in Treatment of Spontaneous Intracerebral Hemorrhage, sponsored by First Affiliated Hospital of Fujian Medical University. Recruiting at 1 site in China. Open to participants aged 40 Years and older. Per ClinicalTrials.gov, last updated 2025-02-12.
Sponsored by First Affiliated Hospital of Fujian Medical University · Not applicable, Interventional, and Treatment
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.
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.
476 studies on the registry are indexed under Cerebral Hemorrhage; 181 are open to participants now.
This study's planned enrollment of 400 is above the median of 100 across 287 interventional studies indexed under Cerebral Hemorrhage.
Browse Cerebral Hemorrhage studies →First Affiliated Hospital of Fujian Medical University is the lead sponsor of 92 studies on the registry; 55 are open to participants now.
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Exclusion Criteria:
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.
Procedure: STAPLE
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.
Stereotactic aspiration plus urokinase clot irrigation
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.
Time frame: At day 365 after randomization
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.
Time frame: 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.
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
Mortality rate as measured by death of a participant \[binary outcome (yes/no)\]. Death induced by any cause.
Time frame: At 365 days after randomization
Plan to share: No — We will share individual participant data after the primary results have been published.
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First Affiliated Hospital of Fujian Medical University