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| Name | Class |
|---|---|
| Xi'an No.3 Hospital | OTHER_GOV |
| Xi'an Gaoxin Hospital | OTHER |
| First People's Hospital of Xianyang | OTHER |
| Xi'an XD Group Hospital |
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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Minocycline treatment group | Experimental | 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. |
|
| Routine treatment group | No Intervention | Patients were given mechanical thrombectomy and other standard treatment for acute ischemic stroke, without minocycline treatment. |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Minocycline | Drug | 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. |
| Measure | Description | Time Frame |
|---|---|---|
| Change in infarct volume from baseline to day 5 | Baseline infarct volume is measured by diffusion-weighted imaging (DWI), day 5 infarct volume is measured by fluid attenuated inversion recovery (FLAIR), Images are processed by imSTROKE software. | Day 5 after onset |
| 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 |
| Measure | Description | Time Frame |
|---|---|---|
| Safety outcomes: adverse events and serious adverse events | Safety outcomes were incidences of adverse events and serious adverse events that were related or not related to the study treatment. | 3 months after onset |
Inclusion Criteria:
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Wen Jiang, Ph.D | Contact | 86-029-84771319 | jiangwen@fmmu.edu.cn | |
| Fang Yang, Ph.D | Contact | 86-029-84771319 | fyangx@fmmu.edu.cn |
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Xijing Hospital | Recruiting | Xi'an | China |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 18815396 | Background | Hacke W, Kaste M, Bluhmki E, Brozman M, Davalos A, Guidetti D, Larrue V, Lees KR, Medeghri Z, Machnig T, Schneider D, von Kummer R, Wahlgren N, Toni D; ECASS Investigators. Thrombolysis with alteplase 3 to 4.5 hours after acute ischemic stroke. N Engl J Med. 2008 Sep 25;359(13):1317-29. doi: 10.1056/NEJMoa0804656. | |
| 16497985 | Background |
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| ID | Term |
|---|---|
| D000083242 | Ischemic Stroke |
| C562573 | cyclopia sequence |
| ID | Term |
|---|---|
| D020521 | Stroke |
| D002561 | Cerebrovascular Disorders |
| D001927 | Brain Diseases |
| D002493 | Central Nervous System Diseases |
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| ID | Term |
|---|---|
| D008911 | Minocycline |
| ID | Term |
|---|---|
| D013754 | Tetracyclines |
| D009279 | Naphthacenes |
| D011084 | Polycyclic Aromatic Hydrocarbons |
| D006841 | Hydrocarbons, Aromatic |
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| UNKNOWN |
| Baoji High-tech Hospital | UNKNOWN |
| Weinan Central Hospital | OTHER |
| Xi'An Daxing Hospital | UNKNOWN |
| Yan'an University Xianyang Hospital | UNKNOWN |
| The First Hospital of Yulin | UNKNOWN |
| Northwest University First Hospital | UNKNOWN |
| Jingyang County Hospital | UNKNOWN |
| Yulin No.2 Hospital | OTHER |
| Yan'an People's Hospital | OTHER |
| Yuncheng Central Hospital | OTHER |
| Second Affiliated Hospital of Xi'an Jiaotong University | OTHER |
| Xi'an No.9 Hospital | UNKNOWN |
| First Affiliated Hospital Xi'an Jiaotong University | OTHER |
| Pucheng County Hospital | UNKNOWN |
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In this study, the outcome of minocycline group and routine treatment group was compared. Placebo control was not used, so outcomes assessor blind was used.
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 5 after onset | Day 5 infarct volume is measured by fluid attenuated inversion recovery (FLAIR). Images are processed by imSTROKE software. | Day 5 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 |
| Yenari MA, Xu L, Tang XN, Qiao Y, Giffard RG. Microglia potentiate damage to blood-brain barrier constituents: improvement by minocycline in vivo and in vitro. Stroke. 2006 Apr;37(4):1087-93. doi: 10.1161/01.STR.0000206281.77178.ac. Epub 2006 Feb 23. |
| 19807907 | Background | Matsukawa N, Yasuhara T, Hara K, Xu L, Maki M, Yu G, Kaneko Y, Ojika K, Hess DC, Borlongan CV. Therapeutic targets and limits of minocycline neuroprotection in experimental ischemic stroke. BMC Neurosci. 2009 Oct 6;10:126. doi: 10.1186/1471-2202-10-126. |
| 24059465 | Background | Liao TV, Forehand CC, Hess DC, Fagan SC. Minocycline repurposing in critical illness: focus on stroke. Curr Top Med Chem. 2013;13(18):2283-90. doi: 10.2174/15680266113136660160. |
| 25889169 | Background | Yang Y, Salayandia VM, Thompson JF, Yang LY, Estrada EY, Yang Y. Attenuation of acute stroke injury in rat brain by minocycline promotes blood-brain barrier remodeling and alternative microglia/macrophage activation during recovery. J Neuroinflammation. 2015 Feb 10;12:26. doi: 10.1186/s12974-015-0245-4. |
| 27560521 | Background | Muhammad S, Planz O, Schwaninger M. Increased Plasma Matrix Metalloproteinase-9 Levels Contribute to Intracerebral Hemorrhage during Thrombolysis after Concomitant Stroke and Influenza Infection. Cerebrovasc Dis Extra. 2016;6(2):50-9. doi: 10.1159/000447750. Epub 2016 Aug 25. |
| 20705929 | Background | Fagan SC, Waller JL, Nichols FT, Edwards DJ, Pettigrew LC, Clark WM, Hall CE, Switzer JA, Ergul A, Hess DC. Minocycline to improve neurologic outcome in stroke (MINOS): a dose-finding study. Stroke. 2010 Oct;41(10):2283-7. doi: 10.1161/STROKEAHA.110.582601. Epub 2010 Aug 12. |
| 17909152 | Background | Lampl Y, Boaz M, Gilad R, Lorberboym M, Dabby R, Rapoport A, Anca-Hershkowitz M, Sadeh M. Minocycline treatment in acute stroke: an open-label, evaluator-blinded study. Neurology. 2007 Oct 2;69(14):1404-10. doi: 10.1212/01.wnl.0000277487.04281.db. |
| 28229893 | Background | Elkins J, Veltkamp R, Montaner J, Johnston SC, Singhal AB, Becker K, Lansberg MG, Tang W, Chang I, Muralidharan K, Gheuens S, Mehta L, Elkind MSV. Safety and efficacy of natalizumab in patients with acute ischaemic stroke (ACTION): a randomised, placebo-controlled, double-blind phase 2 trial. Lancet Neurol. 2017 Mar;16(3):217-226. doi: 10.1016/S1474-4422(16)30357-X. Epub 2017 Feb 15. |
| 29129157 | Background | Nogueira RG, Jadhav AP, Haussen DC, Bonafe A, Budzik RF, Bhuva P, Yavagal DR, Ribo M, Cognard C, Hanel RA, Sila CA, Hassan AE, Millan M, Levy EI, Mitchell P, Chen M, English JD, Shah QA, Silver FL, Pereira VM, Mehta BP, Baxter BW, Abraham MG, Cardona P, Veznedaroglu E, Hellinger FR, Feng L, Kirmani JF, Lopes DK, Jankowitz BT, Frankel MR, Costalat V, Vora NA, Yoo AJ, Malik AM, Furlan AJ, Rubiera M, Aghaebrahim A, Olivot JM, Tekle WG, Shields R, Graves T, Lewis RJ, Smith WS, Liebeskind DS, Saver JL, Jovin TG; DAWN Trial Investigators. Thrombectomy 6 to 24 Hours after Stroke with a Mismatch between Deficit and Infarct. N Engl J Med. 2018 Jan 4;378(1):11-21. doi: 10.1056/NEJMoa1706442. Epub 2017 Nov 11. |
| 42305108 | Derived | Zhang X, Wei D, Li Y, Zhang H, Yao L, Yuan X, Liu W, Ma X, Wang B, Qin N, Li D, Shi R, Fan Z, Wang X, Wang L, Liu Z, Wang L, Wang D, Zhao J, Jiang W; MIST-A Study Group. Efficacy and safety of minocycline on patients with acute anterior circulation ischaemic stroke undergoing mechanical thrombectomy (MIST-A): a multicentre, prospective, randomised, open-label, blinded-endpoint, phase 2 trial. Lancet Reg Health West Pac. 2026 Jun 5;71:101898. doi: 10.1016/j.lanwpc.2026.101898. eCollection 2026 Jun. |
| 39806586 | Derived | Zhang X, Zhao J, Sun Z, Wei D, Yao L, Li W, Zhu H, Liu W, Zhang H, Yuan X, Ma X, Meng J, Wang B, Jia Y, Qin N, Jiang W; MIST-A Study Group. Effects of minocycline on patients with acute anterior circulation ischaemic stroke undergoing intravenous thrombectomy (MIST-A): the study protocol for a multicentre, prospective, randomised, open-label, blinded-endpoint trial. BMJ Open. 2024 Dec 20;14(12):e093443. doi: 10.1136/bmjopen-2024-093443. |
| D009422 |
| Nervous System Diseases |
| D014652 | Vascular Diseases |
| D002318 | Cardiovascular Diseases |
| D006844 |
| Hydrocarbons, Cyclic |
| D006838 | Hydrocarbons |
| D009930 | Organic Chemicals |
| D011083 | Polycyclic Compounds |