Inclusion Criteria:

• Spontaneous supratentorial ICH ≥ 30 mL diagnosed using radiographic imaging (computerized tomography (CT), computerized tomography angiography (CTA), etc.), with a Glasgow Coma Scale (GCS) ≤ 14 or a NIHSS ≥ 6.
• Six-hour clot size equal to the most previous clot size (within 5 mL) as determined by additional CT scans at least 6 hours apart using the ABC/2 method.
• Symptoms less than 24 hours prior to diagnostic CT (dCT) scan (an unknown time of onset is exclusionary).
• Ability to randomize between 12 and 72 hours after dCT.
• Systolic Blood Pressure (SBP) < 180 mmHg sustained for six hours recorded closest to the time of randomization.
• Historical Rankin score of 0 or 1.
• Age ≥ 18 and older.

Exclusion Criteria:

• Infratentorial hemorrhage.
• Intraventricular hemorrhage (IVH) requiring treatment for IVH-related (casting) mass effect or shift due to trapped ventricle. External ventricular drain (EVD) to treat intracranial pressure (ICP) is allowed.
• Thalamic bleeds with apparent midbrain extension with third nerve palsy or dilated and non-reactive pupils. Other (supranuclear) gaze abnormalities are not exclusions. Note: Patients with a posterior fossa ICH or cerebellar hematomas are ineligible.
• Irreversible impaired brain stem function (bilateral fixed, dilated pupils and extensor motor posturing), GCS ≤ 4.
• Ruptured aneurysm, arteriovenous malformation (AVM), vascular anomaly, Moyamoya disease, hemorrhagic conversion of an ischemic infarct, recurrence of a recent (< 1 year) hemorrhage diagnosed with radiographic imaging.
• Patients with unstable mass or evolving intracranial compartment syndrome.
• Platelet count < 100,000, international normalized ratio (INR) > 1.4, or an elevated prothrombin time (PT) or activated partial thromboplastin time (aPTT).
• Any irreversible coagulopathy or known clotting disorder.
• Inability to sustain INR ≤ 1.4 using short- and long-active procoagulants (such as but not limited to NovoSeven, Fresh Frozen Plasma (FFP), and/or vitamin K).
• Subjects requiring long-term anti-coagulation are excluded. Reversal of anti-coagulation is permitted for medically stable patients who can realistically tolerate the short term risk of reversal. Patient must not require Coumadin (anticoagulation) during the first 30 days, and normalized coagulation parameters must be demonstrated, monitored closely and maintained during the period of brain instrumentation.
• Use of Dabigatran, Apixaban, and/or Rivaroxaban (or a similar medication from the similar medication class) prior to symptom onset.
• Internal bleeding, involving retroperitoneal sites, or the gastrointestinal, genitourinary, or respiratory tracts.
• 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.
• Positive urine or serum pregnancy test in pre-menopausal female subjects without a documented history of surgical sterilization.
• Allergy/sensitivity to rt-PA.
• Prior enrollment in the study.
• Participation in a concurrent interventional medical investigation or clinical trial. Patients in observational, natural history, and/or epidemiological studies not involving an intervention are eligible.
• Not expected to survive to the day 365 visit due to co-morbidities and/or are do not resuscitate (DNR)/ do not intubate (DNI) status prior to randomization.
• Any concurrent serious illness that would interfere with the safety assessments including hepatic, renal, gastroenterologic, respiratory, cardiovascular, endocrinologic, immunologic, and hematologic disease.
• Patients with a mechanical heart valve. Presence of bio-prosthetic valve(s) is permitted.
• Known risk for embolization, including history of left heart thrombus, mitral stenosis with atrial fibrillation, acute pericarditis, or subacute bacterial endocarditis.
• Any other condition that the investigator believes would pose a significant hazard to the subject if the investigational therapy were initiated.
• Active drug or alcohol use or dependence that, in the opinion of the site investigator, would interfere with adherence to study requirements.
• In the investigator's opinion, the patient is unstable and would benefit from a specific intervention rather than supportive care plus or minus MIS+rt-PA removal of the ICH.
• Inability or unwillingness of subject or legal guardian/representative to give written informed consent.