TrIal of Early Minimally Invasive Catheter Evacuation With Thrombolysis in IntraCerebral Hemorrhage

Patients presenting to the emergency department with stroke due to supratentorial, spontaneous intracerebral hemorrhage ≥20mL volume will be assessed to determine their eligibility for randomization into the trial. If the patient gives informed consent they will be randomized 1:1 using central computerized allocation to early minimally invasive surgery with thrombolysis versus best medical management. The trial is prospective, randomized, open-label, blinded endpoint (PROBE) design. Adaptive sample size re-estimation will be performed when 250 patients have completed 180 days follow-up. Clinical efficacy will be determined by demonstrating an improvement in functional outcome, as determined by a blinded-assessment of the 180-day utility-weighted modified Rankin Scale (mRS).

Inclusion criteria

• Age ≥ 18 years;
• Pre-randomization head CT demonstrating an acute, spontaneous, primary ICH;
• ICH volume ≥ 20mL as calculated by the ABC/2 method;
• The randomization can be completed within 8 hours after the onset of stroke symptoms (or the time last known to be well), and study intervention can reasonably be initiated within 4 hours after randomization.
• Historical Modified Rankin Score 0 or 1;
• Obtain informed consent from patient or legal representative.

Exclusion criteria

• Infratentorial intraparenchymal hemorrhage including midbrain, pontine, or cerebellar;
• Ruptured aneurysm, arteriovenous malformation (AVM), vascular anomaly, Moyamoya disease, venous sinus thrombosis, mass or tumor, hemorrhagic conversion of an ischemic infarct, tumor stroke, recurrence of a recent (<1 year) ICH, as diagnosed with radiographic imaging;
• Presence of spot sign in CT angiography;
• Blood pressure control before randomization is ineffective, systolic blood pressure > 220 mmHg;
• Irreversible impaired brain stem function (bilateral fixed, dilated pupils and extensor motor posturing), GCS ≤ 4;
• Hemorrhage with apparent midbrain extension with third nerve palsy or dilated and non-reactive pupils. Other (supranuclear) gaze abnormalities are not exclusions;
• Intraventricular extension of the Hemorrhage is visually estimated to involve >50% of either of the lateral ventricles;
• Any irreversible coagulopathy or known clotting disorder.
• Platelet count < 750,000, INR > 1.4 after correction
• Patients requiring long-term anti-coagulation that needs to be initiated < 30 days from index ICH;
• Use of 2 or more antithrombotic drugs prior to symptom onset;
• Patients with a mechanical heart valve;
• Positive urine or serum pregnancy test in female subjects without documented history of surgical sterilization or is post-menopausal;
• Urokinase allergy;
• Any concurrent serious illness that would interfere with the outcome assessments including hepatic, renal, gastroenterologic, respiratory, cardiovascular, endocrinologic, immunologic, and hematologic disease;
• Inability or unwillingness of patient or legal representative to give written informed consent;
• Known life-expectancy of less than 6 months;
• Participation in a concurrent interventional medical investigation or clinical trial.