Effects of Minocycline on Patients With Ischemic Stroke Undergoing Intravenous Thrombectomy

NCT05487417 | Recruiting Phase 4 DMC

• 1 other identifier: XJLL-KY20222186
• Study Type: interventional
• Target: 180
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Ischemic Stroke, Acute

Keywords

Ischemic Stroke; Minocycline; Mechanical thrombectomy; Anterior circulation; Neuroprotection

Outcome Measures

Primary Outcomes (1)

• 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

Secondary Outcomes (9)

• Functional outcome at 3 months after onset

  3 months after onset

• Favourable outcome at 3 months after onset

  3 months after onset

• Excellent outcome at 3 months after onset

  3 months after onset

• Improvement of neurological function compared with baseline

  day 1, day 3, day 5, day 7, and 3 months after onset

• Improvement of activity of daily living at 3 months after onset

  3 months after onset

Other Outcomes (1)

• Safety outcomes: adverse events and serious adverse events

  3 months after onset

Study Arms (2)

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.

Drug: Minocycline

Routine treatment group

NO INTERVENTION

Patients were given mechanical thrombectomy and other standard treatment for acute ischemic stroke, without minocycline treatment.

Interventions

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.

Minocycline treatment group

Eligibility Criteria

• Age: 18 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients with acute cerebral infarction of anterior circulation accompanied by large vessel occlusion;
• Age 18-85 years old;
• The time of onset ≤ 6 hours or ≤ 24 hours suitable for mechanical thrombectomy determined by multimodal imaging;
• The time of onset 6-24 hours, DWI shows an infarct volume less than 1/3 of the MCA blood supply area; the time of onset ≤ 6 hours, the ASPECTS(Alberta Stroke Program Early CT Score) is ≥6;
• Preoperative NIHSS score ranges from 6 to 30 points;
• Sign the informed consent form;

You may not qualify if:

• There are contraindications for mechanical thrombectomy;
• No revascularization therapy was performed during the operation or the TICI score after revascularization therapy was less than 2b;
• There are other major central nervous system diseases, such as brain injury, brain tumor, multiple sclerosis, etc;
• There is evidence that the patient has bacterial endocarditis, aortic dissection, arteritis or venous cerebral infarction;
• Renal insufficiency or hepatic insufficiency (serum creatinine \>2.0 mg/dL or 180 µmol/L; liver function greater than 3 times the normal value);
• Known history of congestive heart failure (requiring dietary or medication changes or hospitalization) within 6 months, or myocardial infarction within 6 months;
• There is evidence of any other life-threatening or severe diseases that may hinder the completion of the 3-month follow-up and affect the evaluation of the results;
• Pre-existing neurological deficits or history of dementia;
• There are infectious diseases that require antibiotic treatment before the disease;
• Allergic to tetracyclines or unable to take minocycline for other reasons;
• Minocycline could not be given within 1 hour after recanalization;
• Pregnant patients;
• Refuse to sign the informed consent form.

Sponsors & Collaborators

• Xijing Hospital: lead
• Xi'an No.3 Hospital: collaborator
• Xi'an Gaoxin Hospital: collaborator
• First People's Hospital of Xianyang: collaborator
• Xi'an XD Group Hospital: collaborator
• Baoji High-tech Hospital: collaborator
• Weinan Central Hospital: collaborator
• Xi'An Daxing Hospital: collaborator
• Yan'an University Xianyang Hospital: collaborator
• The First Hospital of Yulin: collaborator
• Northwest University First Hospital: collaborator
• Jingyang County Hospital: collaborator
• Yulin No.2 Hospital: collaborator
• Yan'an people's Hospital: collaborator
• Yuncheng Central Hospital: collaborator
• Second Affiliated Hospital of Xi'an Jiaotong University: collaborator
• Xi'an No.9 Hospital: collaborator
• First Affiliated Hospital Xi'an Jiaotong University: collaborator
• Pucheng County Hospital: collaborator

Study Sites (1)

Xijing Hospital

Xi'an, China

RECRUITING

Related Publications (11)

• 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.

  PMID: 18815396 BACKGROUND

• 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.

  PMID: 16497985 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.

  PMID: 19807907 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.

  PMID: 24059465 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.

  PMID: 25889169 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.

  PMID: 27560521 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.

  PMID: 20705929 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.

  PMID: 17909152 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.

  PMID: 28229893 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.

  PMID: 29129157 BACKGROUND

• 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.

  PMID: 39806586 DERIVED

MeSH Terms

Conditions

Ischemic Stroke; cyclopia sequence

Interventions

Minocycline

Condition Hierarchy (Ancestors)

Stroke; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Tetracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds

Central Study Contacts

Wen Jiang, Ph.D

CONTACT

86-029-84771319; jiangwen@fmmu.edu.cn

Fang Yang, Ph.D

CONTACT

86-029-84771319; fyangx@fmmu.edu.cn

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Masking Details: 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.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: July 30, 2022
• First Posted: August 4, 2022
• Study Start: November 1, 2022
• Primary Completion: June 10, 2025
• Study Completion: September 10, 2025
• Last Updated: July 24, 2025

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)