Efficacy and Safety of Mirabegron in Intracerebral Hemorrhage

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.

Study Overview

• Status: Recruiting
• Conditions: Intracerebral Haemorrhage
• Intervention / Treatment: Other: Standard treatment; Drug: Standard treatment+mirabegron

Detailed Description

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

• Study Type: Interventional
• Enrollment (Estimated): 25
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Handong Li; Phone Number: +8615022439149; Email: handongli90@foxmail.com

Study Locations

• China
  • Tianjin
    • Tianjin, Tianjin, China, 300052
      • Recruiting
      • Tianjin Medical University General Hospital
      • Contact: Handong Li; Phone Number: +8615022439149; Email: handongli90@foxmail.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 85 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Male or female patients aged above 18 years old.
2. The volume of the hematoma is 5-30 ml (including the cerebral cortex; Putamen, thalamus, caudate nucleus and related deep tracts; Cerebellar hemorrhage), which determined by CT scan.
3. The onset of cerebral hemorrhage symptoms or the time from last normal to detection is not more than 72 hours.
4. Patients with Glasgow Coma Scale (GCS) score ≥6 and < 12.
5. Before the onset of the disease, function was independent and mRS score<1.
6. Able and willing to sign written informed consent and comply with the requirements of the research protocol.

Exclusion criteria:

1. Multifocal cerebral hemorrhage, brain stem hemorrhage, or ventricular hemorrhage.
2. Secondary cerebral hemorrhage caused by aneurysm, brain tumor, arteriovenous malformation, thrombocytopenia, coagulation disorder, traumatic brain injury, etc.
3. Patients who require hematoma removal surgery or other emergency surgical interventions (such as decompressive craniectomy), or who are critically ill and close to death.
4. Patients who interfere with drug use due to nausea or vomiting.
5. Combined with the following conditions that preclude participation in the study due to other systemic diseases: Severe hepatic or renal impairment, atrial fibrillation or tachycardia, pulmonary infection, severe urinary tract infection, severe urinary tract obstruction, medically uncontrolled hypertension (systolic blood pressure ≥180mmHg or diastolic blood pressure ≥110mmHg), pregnant and lactating women, and a history of malignant tumors within 5 years.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Standard treatment; Patients will receive usual care	Other: Standard treatment; Standard treatment
Experimental: Standard treatment+mirabegron; In addition to standard treatment, the first dose of mirabegron 50mg/day will be given within 72 hours of symptom onset and continued until the 7th day after onset.	Drug: Standard treatment+mirabegron; In addition to standard treatment, the first dose of mirabegron 50mg/day will be given within 72 hours of symptom onset and continued until the 7th day after onset.

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
Changes of immune cells in peripheral blood	The counts of monocytes subsets and other immune cells in peripheral blood were compared.	14 days

Collaborators and Investigators

• Sponsor: Tianjin Medical University General Hospital

Study record dates

Study Major Dates

• Study Start (Actual): January 17, 2024
• Primary Completion (Estimated): August 10, 2026
• Study Completion (Estimated): November 10, 2026

Study Registration Dates

• First Submitted: May 6, 2022
• First Submitted That Met QC Criteria: May 10, 2022
• First Posted (Actual): May 11, 2022

Study Record Updates

• Last Update Posted (Actual): February 13, 2024
• Last Update Submitted That Met QC Criteria: February 9, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Cardiovascular Diseases; Vascular Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Intracranial Hemorrhages; Hemorrhage; Cerebral Hemorrhage; Physiological Effects of Drugs; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Urological Agents; Adrenergic Agonists; Adrenergic beta-Agonists; Adrenergic beta-3 Receptor Agonists; Mirabegron
• Other Study ID Numbers: IRB2022-YX-073-01

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No