Minimally Invasive Surgery and rhTNK-tPA for Intracerebral Hemorrhage Evacuation

Prior treatment

• Subjects necessitating long-term anticoagulation therapy are excluded from participation. Reversal of anticoagulation is permissible for medically stable patients who can feasibly tolerate the short-term risks associated with reversal. Patients must not require Coumadin (warfarin) or other anticoagulants during the initial 30-day period.
• Prior to the onset of symptoms, anticoagulants such as dabigatran, apixaban, or rivaroxaban, as well as treatments like tirofiban, ticagrelor, cilostazol, or clopidogrel, were used.
• Engagement in a concurrent interventional clinical investigation or trial. Patients enrolled in observational, natural history, or epidemiological studies that do not involve any form of intervention remain eligible.
• The presence of any concurrent serious illness that could confound outcome assessments, including but not limited to hepatic, renal, gastroenterologic, respiratory, cardiovascular, endocrinologic, immunologic, or hematologic disorders.
• Any other condition that, in the investigator's judgment, would present a significant risk to the subject if the investigational therapy were to be initiated.
• Active drug or alcohol use or dependence that, in the opinion of the site investigator, would interfere with adherence to study requirements.

Other illness

• Lobar or subtentorial hemorrhage, including posterior fossa hemorrhage and cerebellar hemorrhage.
• Intraventricular hemorrhage necessitating intervention to address mass effect or midline shift attributable to trapped ventricle syndrome secondary to intraventricular hemorrhage (IVH)-related casting.
• 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.
• Patients presenting with an unstable intracranial mass or progressive intracranial compartment syndrome.
• Irreversible impairment of brainstem function, characterized by bilateral fixed and dilated pupils, extensor motor posturing, and a Glasgow Coma Scale (GCS) score of ≤ 4.
• Indications for craniotomy in patients include: 1) progressive impairment of consciousness; 2) presence of brain herniation, with signs related to cerebellar tonsil herniation or temporal lobe gyrus herniation; 3) hematoma located within 1 cm of the cortical surface.
• Any irreversible coagulation disorders (e.g., hemophilia, von Willebrand disease, use of anticoagulants such as warfarin) or known clotting disorders (e.g., hypercoagulable states).
• Internal bleeding involving the retroperitoneal, gastrointestinal, or genitourinary system, or respiratory tract bleeding.
• Superficial or surface bleeding, observed mainly at vascular puncture and access sites (e.g., venous cutdowns, arterial punctures, etc.) or site of recent surgical intervention.
• Allergy/sensitivity to TNK.
• Patients with mechanical heart valves are excluded. The presence of bioprosthetic valve(s) is permissible.
• Known risk for embolization, including history of left heart thrombus, mitral stenosis with atrial fibrillation, acute pericarditis, or subacute bacterial endocarditis. Atrial fibrillation without mitral stenosis is permitted.
• Patients deemed by the investigator to have unstable conditions that may benefit from other treatments.

Lab values

• Platelet count \<100,000/mL; INR \>1.4.
• Inability to maintain INR ≤1.4 using short-acting and long-acting procoagulants (e.g., recombinant human coagulation factor VIIa, fresh frozen plasma, vitamin K, etc.).
• Positive urine or serum pregnancy test in pre-menopausal female subjects without a documented history of surgical sterilization.

Other

• Stability CT scan done at least 6 hours after diagnostic CT showing clot instability (growth ≥5 mL as measured by ABC/2 method).
• 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 exclusion criteria.
• CT evidence suggesting a high risk of rebleeding, such as spot sign.
• Patients requesting conservative treatment or standard craniotomy microsurgery treatment.
  • The subject or their legal guardian/representative demonstrates an inability or lack of willingness to provide written informed consent.

• Age ≥18 years and \<80 years.
• 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.
• 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.).
• Glasgow Coma Scale (GCS) score of 5-14.
• Stability CT scan done at least 6 hours after diagnostic CT showing clot stability (growth \<5 mL as measured by ABC/2 method).
• Neuronavigation-assisted stereotactic MIPS should be performed within 6 to 24 hours after the diagnostic CT.
• 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.