Efficacy and Safety of Minocycline in Acute Spontaneous Intracerebral Hemorrhage (MISTICH)

Capital Medical University

Status and phase: Not yet enrolling; Phase 3

Conditions: Intracerebral Hemorrhage

Treatments: Drug: Placebo capsules of Minocycline hydrochloride capsules; Drug: Minocycline hydrochloride capsules

Study type: Interventional

Funder types: Other

Identifiers

NCT07338175

MISTICH

Details and patient eligibility

About

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.

Full description

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.

Enrollment: 1,192 estimated patients

Sex: All

Ages: 18 to 80 years old

Volunteers: No Healthy Volunteers

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 or those at high risk of hematoma expansion indicated by imaging signs;
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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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1,192 participants in 2 patient groups, including a placebo group

Active Comparator: Minocycline treatment group

Experimental group

Description:

Minocycline Hydrochloride Capsules (50 mg per capsule). The first dose (200mg, 4 capsules) should be given immediately after randomization (within 30 minutes); Subsequently, 100mg (2 capsules) will be administered once every 12 hours; a total of 10 times (lasting 5 days; the subject with dysphagia will be administrated through a nasal feeding tube).

Treatment:

Drug: Minocycline hydrochloride capsules

Placebo Comparator: Minocycline placebo-control group

Placebo Comparator group

Description:

Placebo of Minocycline Hydrochloride capsules (50mg per capsule, containing 0 mg of Minocycline). The method of administration was the same as that of treatment group.

Treatment:

Drug: Placebo capsules of Minocycline hydrochloride capsules