Intracerebral Hemorrhage
Conditions
Keywords
Intracerebral Hemorrhage, Minocycline, Neuroprotection
Brief summary
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.
Detailed 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.
Interventions
50 mg per capsule, containing 50mg of Minocycline Hydrochloride
50 mg per capsule, containing 0 mg of Minocycline Hydrochloride
Sponsors
Beijing Tiantan Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| mRS score 0-3 | At 90±7 days after randomization | Modified Rankin Scale score |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Changes in NIHSS score compared with baseline score | At 72±12 hours and 7±1 days after randomization | NIHSS score |
| Changes in Glasgow Coma Scale score compared with baseline score | At 72±12 hours and 7±1 days after randomization | Glasgow Coma Scale score |
| Early neurological deterioration | At 72±12 hours and 7±1 days after randomization | Early neurological deterioration is defined as a decrease of ≥2 in GCS score or an increase of ≥4 in NIHSS score caused by non-sedatives/sleeping drugs compared with the baseline level. |
| Changes in hs-CRP level compared with baseline level | At 72±12 hours and 7±1 days after randomization | hs-CRP is examined to evaluate the level of systematic inflammation. |
| Volume of perihematomal edema (PHE) | At 7±1 days after randomization | Volume of perihematomal edema (PHE) on MRI |
| EQ-5D-5L utility score | At 90±7 days and 180±7 days after randomization | Quality of life assessed by the EQ-5D-5L utility score |
| Recurrent stroke | At 90±7 days and 180±7 days after randomization | Recurrent stroke includes ischemic stroke and hemorrhagic stroke. |
| Combined vascular events | At 90±7 days and 180±7 days after randomization | Combined vascular events include stroke, myocardial infarction, and vascular death. |
| mRS score | At 90±7 days and 180±7 days after randomization | Modified Rankin Scale score |
Other
| Measure | Time frame | Description |
|---|---|---|
| Hematoma expansion or rebleeding | At 72±12 hours and 7±1 days after randomization | Hematoma expansion or rebleeding |
| Antibiotic-associated diarrhea, enteritis, and constipation | At 7±1 days after randomization | Antibiotic-associated diarrhea, enteritis, and constipation |
| Any bleeding events | At 90±7 days after randomization | Any bleeding events |
| Adverse events (AE) | At 90±7 days after randomization | Adverse events (AE) |
| Serious adverse events (SAE) | At 90±7 days after randomization | Serious adverse events (SAE) |
| Perihematomal blood-brain barrier permeability | At 7±1 days after randomization | Perihematomal blood-brain barrier permeability is assessed using dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI). |
| Changes in the levels of venous neuroinflammation indicators compared with baseline levels | At 72±12 hours and 7±1 days after randomization | Venous neuroinflammation indicators (IL, TNF-α, TGF-β, NFL, etc.) |
Countries
China
Contacts
Primary ContactKaijiang Kang, MD
Outcome results
None listed