Inclusion Criteria:
Participants must meet all the following criteria:
1. Age ≥ 18 and ≤ 80 years
2. Spontaneous supratentorial ICH confirmed by CT or CTA, with hematoma volume:
* ≥30 mL on initial diagnostic CT, OR
* ≥25 mL on stability CT performed ≥6 hours after diagnostic CT,
1. Clot growth must be less than 5 mL between scans to be eligible
2. A second stability scan at least 12 hours later is allowed if clot expanded \>5 mL
3. NIHSS score ≥ 6 at enrollment
4. Glasgow Coma Scale (GCS) score ≥5 and ≤14 at screening
5. Symptoms onset ≤ 24 hours before diagnostic CT
* Use "last known well" for wake-up strokes
* Unknown onset is exclusionary
6. SBP \< 180 mm Hg sustained for at least 6 hours prior to randomization
7. Randomization must occur between 12 and 24 hours from initial diagnostic CT done at UIC or in case of transfers, at other institutions.
8. Functionally independent pre-ICH, defined as mRS 0-1. Pre-ICH functional status will be determined from medical records and structured interviews with the patient or a reliable caregiver, with ambiguous cases adjudicated by the site PI. Patients with mRS 0-1 are considered functionally independent, able to perform all usual activities without assistance.
9. Written informed consent obtained from patient or legal representative
Exclusion Criteria:
1. Infratentorial hemorrhage (e.g., brainstem or cerebellar hematoma).
2. Hemorrhage due to secondary causes: trauma, AVM, aneurysm, Moyamoya disease, hemorrhagic conversion of ischemic stroke, tumor, or vascular anomaly (diagnosed on imaging).
3. Recurrent ICH within the past year.
4. Intraventricular hemorrhage (IVH) requiring surgical treatment for trapped ventricle or mass effects (e.g., endoscopic evacuation). EVD is permitted.
5. Evidence of irreversible impaired brainstem function (e.g., bilateral fixed dilated pupils, decerebrate posturing).
6. Glasgow Coma Scale (GCS) ≤ 4 at screening, indicating extremely poor neurologic prognosis. NIHSS item 1a = 3, indicating comatose status (unresponsive to verbal or painful stimulation).
7. Thalamic ICH with midbrain extension and third nerve palsy.
8. Clinical indication for emergent surgical hematoma evacuation, as determined by treating neurosurgeons.
9. NIHSS score \< 6 (too mild to benefit).
10. Expected withdrawal of care or death within 72 hours.
11. Prior enrollment in the study.
12. Creatinine ≥ 2.0 mg/dL or evidence of severe renal impairment.
13. Active hepatic failure or severe hepatic disease.
14. Pregnancy or breastfeeding.
15. Severe iron deficiency anemia (Hgb \< 8 g/dL or ferritin \<15 ng/mL).
16. Active systemic infection (e.g., sepsis, subacute bacterial endocarditis).
17. Active internal bleeding (GI, GU, retroperitoneal, pulmonary).
18. History of mechanical heart valve (bioprosthetic valves allowed).
19. Known left atrial/ventricular thrombus or high embolic risk (e.g., mitral stenosis + AFib).
20. Any coagulopathy:
* Platelet count \<100,000
* INR \> 1.4 not correctable within 6 hours
* Use of NOACs (apixaban, rivaroxaban, dabigatran) or LMWH at presentation
21. Long-term anticoagulation that cannot be stopped safely (e.g., mechanical valve needing Coumadin).
22. Allergy or intolerance to DFX or rtPA.
23. Active alcohol or drug use that impairs adherence to follow-up.
24. Participation in another interventional trial. (Observational studies are allowed.
25. Inability or unwillingness to provide informed consent. This includes patients who lack decision-making capacity (and have no available legally authorized representative) or those who decline participation.
26. Not expected to survive to Day 365 or have DNR/DNI status at time of screening.
27. Any other condition that the investigator believes would pose a significant hazard or interfere with outcome assessments.
28. Patients with confirmed aspiration, pneumonia, pulmonary edema, evident bilateral pulmonary infiltrates on CXR or CT scan prior to enrollment.
29. Patients with significant respiratory disease such as chronic obstructive pulmonary disease, pulmonary fibrosis, or any use of chronic or intermittent inhaled O2 at home.
30. The presence of 4 or more of the following risk modifiers for ARDS prior to enrollment:
1. Tachypnea (respiratory rate \>30)
2. SpO2 \<95%
3. Obesity, defined as Body Mass Index (BMI) \>30 d) Acidosis (pH \<7.35)
e. Hypoalbuminemia (albumin \<3.5 g/dL) f. Concurrent use of chemotherapy
31. Subjects who are taking prochlorperazine or are expected to undergo Gallium-67 imaging during the study period.
32. Known severe hearing loss.
33. Taking iron supplements containing ≥325 mg ferrous iron or prochlorperazine 34. Patients with heart failure taking \>500 mg vitamin C daily
