Treatment of Spontaneous Intracerebral Hemorrhage Clinical Trial
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 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. 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. ;