Efficacy and Safety of Mirabegron in Intracerebral Hemorrhage

Study Overview
=================
Brief Summary
-----------------
Intracerebral hemorrhage (ICH) accounts for 10-15% of all strokes without effective pharmacological treatment. Inflammation following ICH contributes to barrier disruption and peri-hematoma edema, leading to deterioration of neurological function. Preclinical evidence suggests that bone marrow hematopoietic stem and progenitor cells (HSPCs) are swiftly activated after ICH. Thereafter, these HSPCs produce an increased output of anti-inflammatory monocytes as an endogenous protective mechanism. Stimulation of β3 adrenergic receptor using selective agonists promotes the production of anti-inflammatory monocytes in bone marrow, and thereby reduces neuroinflammation, brain edema and neurological deficits. This study is to assess the safety and efficacy of a β3 adrenergic receptor agonist Mirabegron as a potential treatment option in ICH patients.

Detailed Description
-----------------
This study is to evaluate the efficacy and safety of mirabegron in patients with intracerebral hemorrhage based on standard therapy

Official Title
-----------------
Efficacy and Safety of Mirabegron in Intracerebral Hemorrhage

Conditions
-----------------
Intracerebral Haemorrhage

Intervention / Treatment
-----------------
* Drug: mirabegron
* Other: usual care


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: 1. Male or female patients aged 18 to 85 years (inclusive). 2. Written informed consent obtained before any study assessment is performed. If the patient is not able to give the informed consent personally, consent by a relative or legal representative is acceptable. 3. Spontaneous, supratentorial intracerebral hemorrhage in cerebral cortex or deep brain structures (putamen, thalamus, caudate, and associated deep white matter tracts) with a volume ≥ 10 mL but ≤ 30 mL (calculated by the ABC/2 method) determined by routine clinical CT. 4. Patients with the onset of ICH witnessed and/or last seen healthy no longer than 24 hrs previously. 5. Patients with Glasgow Coma Scale (GCS) no less than 6. 6. Before the onset of the disease, function was independent, mRS score<2. Exclusion Criteria: 1. Infratentorial (midbrain, pons, medulla, or cerebellum) ICH. 2. Secondary ICH due to aneurysm, brain tumor, arteriovenous malformation, thrombocytopenia, coagulopathy, acute sepsis, traumatic,brain injury (TBI), or disseminated intravascular coagulation (DIC). 3. Candidates for surgical hematoma evacuation or other urgent surgical intervention (i.e., surgical relief of increased intracranial pressure). 4. Intraventricular hemorrhage. 5. Severe liver and kidney dysfunction. 6. Hypertension that cannot be controlled by drugs (systolic blood pressure≥180mmHg or diastolic blood pressure≥110mmHg). 7. Urinary tract infection. 8. Difficulty swallowing, nausea, and vomiting, resulting in difficulty taking mirabegron on orally. 9. Pregnancy and lactation. 10. Patients with malignant tumor.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 85 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Standard treatment+mirabegron<br>In addition to standard treatment, mirabegron 50 mg/d will be given as the first dose within 24 hours of symptom onset for 14 consecutive days. | Drug: mirabegron<br>* In addition to standard treatment, mirabegron 50 mg/d will be given as the first dose within 24 hours of symptom onset for 14 consecutive days.<br>Other: usual care<br>* usual care<br>|
| Placebo Comparator: Control group<br>Patients will receive usual care | Other: usual care<br>* usual care<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in absolute perihematomal edema volume measured by computed tomography (CT) | Repeated CT images will be obtained at 24-48 hours after diagnosis and on days 7 and 14 with CT at 24-48 hours after diagnosis as the baseline for analysis. | 7 and 14 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in absolute hematoma volume measured by CT after ICH | Repeated CT images will be obtained at 24-48 hours after diagnosis and on days 7 and 14 with CT at 24-48 hours after diagnosis as the baseline for analysis. | 7 and 14 days | 
| Changes in NIHSS scores | The assessment will be based on the National Institutes of Health Stroke Scale (NIHSS) with a score range of 0 (asymptomatic) to 42 (death). | 7 and 14 days | 
| The rate of functional independence at 90 days | Number of participants with functional independence. Modified Rankin scale (mRS) is a scale for measuring the degree of disability or dependence in the daily activities of people who have suffered a stroke or other causes neurological disability. Functional Independence: 0 - no symptoms at all 1 - no significant disability despite symptoms; able to carry out all usual duties and activities 2- slight disability; unable to carry out all previous activities, but able to look after own affairs without assistance | 90 days | 
| Proportion of adverse drug reactions | Adverse events related to mirabegron will be recorded. | 14 days | 
| All cause mortality | Death induced by any cause | 90 days |