Effects of Minocycline on Patients With Ischemic Stroke Undergoing Intravenous Thrombectomy

Study Overview
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Brief Summary
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Minocycline is the second generation of tetracycline. Because of its lipophilicity, it has high penetrance of blood-brain barrier. Animal model studies have shown that minocycline can reduce cerebral damage after ischemic stroke, and its mechanism involves multiple molecular pathways, such as antioxidant, anti-inflammatory, anti apoptotic pathways, and protection of blood-brain barrier. Clinical studies have also shown that minocycline can significantly improve 3-month National Institute of Health Stroke Scale (NIHSS) and modified Rankin Scale (mRS) of patients with ischemic stroke, indicating that minocycline is a potential neuroprotective drug. Minocycline is believed to protect the blood-brain barrier, thereby reducing the ischemia-reperfusion injury caused by mechanical thrombectomy. However, whether minocycline can become a synergistic treatment method of mechanical thrombectomy, there is no clinical research in this area at present. Therefore, investigators carry out the study on the effect of minocycline in patients with acute anterior circulation ischemic stroke after mechanical thrombectomy, and plan to enroll 180 patients. To explore the safety and effectiveness of minocycline in patients with acute ischemic stroke after thrombectomy.

Official Title
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Effects of Minocycline on Patients With Acute Anterior Circulation Ischemic Stroke Undergoing Intravenous Thrombectomy

Conditions
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Ischemic Stroke, Acute

Intervention / Treatment
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* Drug: Minocycline


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with acute cerebral infarction of anterior circulation accompanied by large vessel occlusion; Age ≥ 18 years old; The time of onset ≤ 6 hours or ≤ 24 hours suitable for mechanical thrombectomy determined by multimodal imaging; Sign the informed consent form; Exclusion Criteria: There are contraindications for mechanical thrombectomy; There are other major central nervous system diseases, such as brain injury, brain tumor, multiple sclerosis, etc; There was a history of neurological impairment or dementia before the stroke; Chronic renal failure; There are infectious diseases requiring antibiotic treatment; Allergic to tetracyclines or unable to take minocycline for other reasons; Pregnant patients; Refuse to sign the informed consent form.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Minocycline treatment group<br>Patients were given minocycline 200mg/d orally from the day of admission for 5 days. At the same time, the patient received mechanical thrombectomy and other standard treatments for acute ischemic stroke. | Drug: Minocycline<br>* Minocycline is a tetracycline antibiotic. Previous studies have confirmed that its application in stroke patients has good efficacy and safety, suggesting that it could become a synergistic treatment of mechanical thrombectomy.<br>|
| No Intervention: Routine treatment group<br>Patients were given mechanical thrombectomy and other standard treatment for acute ischemic stroke, without minocycline treatment. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in infarct volume from baseline to day 7 | Baseline infarct volume is measured by diffusion-weighted imaging (DWI), day 7 infarct volume is measured by fluid attenuated inversion recovery (FLAIR), Images are processed by imSTROKE software. | Day 7 after onset | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Functional outcome at 3 months after onset | Defined by the modified Rankin Scale (mRS), which ranges from 0 (no symptoms) to 6 (death), analyzed for superiority and then for noninferiority. | 3 months after onset | 
| Favourable outcome at 3 months after onset | Defined as proportion of patients with modified Rankin Scale (mRS) 0-2, which ranges from 0 (no symptoms) to 6 (death), An mRS score of <3 indicated a favourable outcome, whereas a score of ≥3 indicated a poor outcome. | 3 months after onset | 
| Excellent outcome at 3 months after onset | Defined as proportion of patients with modified Rankin Scale (mRS) 0-1, which ranges from 0 (no symptoms) to 6 (death), An mRS score of <2 indicated a excellent outcome, whereas a score of ≥2 indicated a poor outcome. | 3 months after onset | 
| Improvement of neurological function compared with baseline | Defined by the National Institute of Health Stroke Scale (NIHSS), which ranges from 0 (no neurological injury) to 42 (severe neurological injury). The assessment time points were baseline, day 1, day 3, day 5, day 7, and 3 months after onset. | day 1, day 3, day 5, day 7, and 3 months after onset | 
| Improvement of activity of daily living at 3 months after onset | Defined by Barthel index (BI), which ranges from 0 (completely lose the ability to live independently) to 100 (complete ability to live independently). The assessment time points were 3 months after onset | 3 months after onset | 
| Incidence of intracranial hemorrhage at day 1 after onset | Intracranial hemorrhage is measured by CT scan. Images are processed by RAPID ICH software. | Day 1 after onset | 
| Mortality at 3 months after onset | The investigators record all-cause mortality | 3 months after onset | 
| Infarct volume at day 7 after onset | Day 7 infarct volume is measured by fluid attenuated inversion recovery (FLAIR). Images are processed by imSTROKE software. | Day 7 after onset | 
| Length of hospital stay and length of Intensive Care Unit (ICU) stay | How long the patients stay in hospital, and how long the patients stay in ICU | 3 months after onset | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Ischemic Stroke, Minocycline, Mechanical thrombectomy, Anterior circulation, Neuroprotection