Cerebral Hemorrhage, Cerebrovascular Disorders, Hemorrhage, Intracranial Hemorrhages
Conditions
Keywords
Basal ganglia, Stereotactic puncture therapy, Cerebral Hemorrhage, rhTNK-tPA, Minimally Invasive Surgery
Brief summary
The purpose of this trial is to determine the safety of using a combination of robot-assisted stereotactic puncture and clot lysis with rhTNK-tPA to remove intracerebral hemorrhage (ICH) and to provide dose evidence for a phase III clinical trial.
Detailed description
Minimally invasive puncture surgery (MIPS) is a recommended effective surgical treatment method by the new guidelines to improve the mortality rate of intracerebral hemorrhage patients. It is easy to operate and has the conditions for widespread implementation. Stereotactic puncture is the least invasive treatment method, which can reduce the effect of hematoma occlusion and cytotoxicity and maximize the protection of neurological function. The MISTIE III study published in The Lancet showed that the mortality rate of the group treated with minimally invasive intracerebral hematoma evacuation combined with alteplase was reduced at 365 days, but the functional prognosis was not improved. Alteplase may have poor fibrin specificity, a short half-life, and a weak effect on PAI-1, resulting in incomplete blood clot dissolution, which may be the reason for poor prognosis. Tenecteplase (rhTNK-tPA), a third-generation specific fibrinolytic agent, is used for intravenous thrombolysis in acute ischemic stroke and has higher fibrin specifc. The study design is an open-label, non-comparative, phase 1 dose escalation protocol.The purpose of this trial is to determine the safety of using a combination of robot-assisted stereotactic puncture and clot lysis with rhTNK-tPA to remove intracerebral hemorrhage (ICH) and to provide dose evidence for a phase III clinical trial.
Interventions
DRUGMinimally invasive surgery plus low-dose rhTNK-tPA group
The calculated injection amount of teneplase (teneplase injection amount = volume of hematoma ×0.001mg) was diluted to 1ml with sterile injection water, and injected into the stereotaxically planned puncture path according to the location and size of the hematoma. The pipeline was rinsed with 0.5ml normal saline, and the drainage tube was fixed and closed for 2 hours, so that after the full effect of the drug on the hematoma mass was ensured. Re-open the drain to allow gravity drainage.
DRUGMinimally invasive surgery plus medium dose rhTNK-tPA group
The calculated injection amount of teneplase (teneplase injection amount = volume of hematoma ×0.003mg) was diluted to 1ml with sterile injection water, and injected into the stereotaxically planned puncture path according to the location and size of the hematoma. The pipeline was rinsed with 0.5ml normal saline, and the drainage tube was fixed and closed for 2 hours, so that after the full effect of the drug on the hematoma mass was ensured. Re-open the drain to allow gravity drainage.
DRUGMinimally invasive surgery plus high dose rhTNK-tPA group
The calculated injection amount of teneplase (teneplase injection amount = volume of hematoma ×0.009mg) was diluted to 1ml with sterile injection water, and injected into the stereotaxically planned puncture path according to the location and size of the hematoma. The pipeline was rinsed with 0.5ml normal saline, and the drainage tube was fixed and closed for 2 hours, so that after the full effect of the drug on the hematoma mass was ensured. Re-open the drain to allow gravity drainage.
Sponsors
Beijing Tiantan Hospital
Study design
Allocation
NA
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
1. Age ≥18 years and \<80 years. 2. Symptoms must have manifested within 24 hours prior to the diagnostic CT scan. Cases with an indeterminate onset time are excluded. For patients who present symptoms upon sleeping, the last known time they were well should be used. 3. Acute spontaneous deep intracerebral hemorrhage (ICH) occurring in the basal ganglia or thalamus, with a volume between 20-50 mL as measured by ABC/2 method with radiographic imaging (CT, etc.). 4. Glasgow Coma Scale (GCS) score of 5-14. 5. Stability CT scan done at least 6 hours after diagnostic CT showing clot stability (growth \<5 mL as measured by ABC/2 method). 6. Neuronavigation-assisted stereotactic MIPS should be performed within 6 to 24 hours after the diagnostic CT. 7. Systolic blood pressure (SBP) less than 180 mmHg maintained for a duration of six hours, documented proximate to the enrollment time point. Historical Rankin score of 0 or 1.
Exclusion criteria
1. Lobar or subtentorial hemorrhage, including posterior fossa hemorrhage and cerebellar hemorrhage. 2. Stability CT scan done at least 6 hours after diagnostic CT showing clot instability (growth ≥5 mL as measured by ABC/2 method). 3. Intraventricular hemorrhage necessitating intervention to address mass effect or midline shift attributable to trapped ventricle syndrome secondary to intraventricular hemorrhage (IVH)-related casting. 4. Hemorrhage attributable to other cerebrovascular pathologies, including but not limited to ruptured aneurysm, arteriovenous malformation (AVM), vascular anomalies, moyamoya disease, hemorrhagic transformation of an ischemic infarct, or recurrence of a recent hemorrhage within the past year, as diagnosed through radiographic imaging. 5. Patients presenting with an unstable intracranial mass or progressive intracranial compartment syndrome. 6. Thalamic hemorrhages exhibiting evident extension into the midbrain, accompanied by oculomotor nerve palsy or pupils that are dilated and non-reactive. Other supranuclear gaze abnormalities do not constitute
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Drug-related rebleeding events: | Within 24 hours of the last dose | CT examinations were performed at 24, 48, 72, and 96 hours after administration. Compared with the CT at the previous time point, a CT value of more than 72 HU and a volume of more than 5 ml found in and around the hematoma cavity were defined as newly emitted blood. |
Countries
China
Outcome results
None listed