This is a prospective, multicenter, randomized, double-blind, placebo-controlled clinical trial. It aims to evaluate the efficacy and safety of oral minocycline in patients with acute spontaneous intracerebral hemorrhage within 48 hours of onset.

The aim of this study was to evaluate the efficacy and safety of 5-day Minocycline versus placebo in patients with acute intracerebral hemorrhage within 48 hours of onset. In addition, we will explore the effect of Minocycline versus placebo on indicators of venous neuroinflammation at different time points in patients with acute intracerebral hemorrhage within 48 hours of onset.

A total of 1192 participants will be randomized 1:1 to receive either minocycline or matching placebo for 5 days, in addition to guideline-based standard medical care.

The primary objective is to evaluate the effect of Minocycline in improving the level of 90-day mRS score to 0-3 in patients with acute intracerebral hemorrhage within 48 hours of onset.

The trial is divided into three phases: screening/baseline period, treatment period, and follow-up period. The visit schedule is as follows: Randomized participants are interviewed at screening/baseline period, 72±12 hours, 7±1 days, 90±7 days,180±7 days after randomization, and when events occur.

Inclusion Criteria:

1. CT-confirmed spontaneous supratentorial intracerebral hemorrhage;
2. Aged 18 to 80 years;
3. Within 48 hours of symptom onset;
4. Hematoma volume 15-40 ml;
5. NIHSS score 8-24, with item 1a ≤ 2;
6. Signed informed consent by the patient or legal representative.

Exclusion Criteria:

1. Secondary intracerebral hemorrhage (traumatic, tumor-related, vascular malformation, aneurysm, coagulation disorder, etc.);
2. Intraventricular hemorrhage filling one entire lateral ventricle, third ventricle, or fourth ventricle, or more than half of two lateral ventricles;
3. Significant subarachnoid hemorrhage (Fisher grade ≥ 3) or subdural hemorrhage;
4. Patients with uncontrollable hypertension ( systolic blood pressure persistently ≥ 180 mmHg despite intensive antihypertensive treatment);
5. Progressive neurological or other severe systemic diseases;
6. Planned surgical intervention for the intracerebral hemorrhage;
7. Pre-stroke disability (modified Rankin Scale score > 1);
8. Severe cardiac insufficiency (NYHA Class III-IV), severe liver disease (ALT or AST > 3 times the normal upper limit value), severe renal insufficiency (serum creatinine > 2 times the normal upper limit value, or glomerular filtration rate < 45 ml/min), or malignancy with life expectancy < 1 year;
9. Moderate to severe anemia (hemoglobin < 90 g/L), thrombocytopenia (platelet count < 100×10^9/L), leukopenia (white blood cell count < 2×10^9/L), or coagulopathy (INR > 1.5);
10. Allergy or intolerance to minocycline or other tetracycline antibiotics;
11. History of pseudomembranous enteritis or antibiotic-associated enteritis;
12. Use of tetracycline antibiotics within the past week;
13. Intracranial or spinal surgery within the past 3 months;
14. Any major surgery or severe physical trauma within the past month;
15. Females who are pregnant, within 30 days postpartum, or in the lactation period.
16. Participated in other interventional clinical trials within the past 3 months;
17. Inability to obtain signed informed consent from the patient or representative;
18. Other conditions that are not suitable for participating in this clinical trial, such as inability to understand and/or follow the research procedures due to mental, cognitive, emotional, or physical disorders, etc.