Efficacy and Safety of Minocycline in Patients With Moderate to Severe Acute Ischemic Stroke

Summary

The aim of this study was to evaluate the efficacy and safety of Minocycline versus placebo in the treatment of patients with moderate to severe acute ischemic stroke.

Timeline

Start

2023-05-19

Primary completion

2024-05-20

Completion

2024-08-15

Publications

• Results Zhou M, Wang H, Zhu J, Chen W, Wang L, Liu S, Li Y, Wang L, Liu Y, Yin P, Liu J, Yu S, Tan F, Barber RM, Coates MM, Dicker D, Fraser M, Gonzalez-Medina D, Hamavid H, Hao Y, Hu G, Jiang G, Kan H, Lopez AD, Phillips MR, She J, Vos T, Wan X, Xu G, Yan LL, Yu C, Zhao Y, Zheng Y, Zou X, Naghavi M, Wang Y, Murray CJ, Yang G, Liang X. Cause-specific mortality for 240 causes in China during 1990-2013: a systematic subnational analysis for the Global Burden of Disease Study 2013. Lancet. 2016 Jan 16;387(10015):251-72. doi: 10.1016/S0140-6736(15)00551-6. Epub 2015 Oct 26.
• Results GBD 2019 Stroke Collaborators. Global, regional, and national burden of stroke and its risk factors, 1990-2019: a systematic analysis for the Global Burden of Disease Study 2019. Lancet Neurol. 2021 Oct;20(10):795-820. doi: 10.1016/S1474-4422(21)00252-0. Epub 2021 Sep 3.
• Results Wardlaw JM, Murray V, Berge E, del Zoppo G, Sandercock P, Lindley RL, Cohen G. Recombinant tissue plasminogen activator for acute ischaemic stroke: an updated systematic review and meta-analysis. Lancet. 2012 Jun 23;379(9834):2364-72. doi: 10.1016/S0140-6736(12)60738-7. Epub 2012 May 23.
• Results Saver JL, Goyal M, van der Lugt A, Menon BK, Majoie CB, Dippel DW, Campbell BC, Nogueira RG, Demchuk AM, Tomasello A, Cardona P, Devlin TG, Frei DF, du Mesnil de Rochemont R, Berkhemer OA, Jovin TG, Siddiqui AH, van Zwam WH, Davis SM, Castano C, Sapkota BL, Fransen PS, Molina C, van Oostenbrugge RJ, Chamorro A, Lingsma H, Silver FL, Donnan GA, Shuaib A, Brown S, Stouch B, Mitchell PJ, Davalos A, Roos YB, Hill MD; HERMES Collaborators. Time to Treatment With Endovascular Thrombectomy and Outcomes From Ischemic Stroke: A Meta-analysis. JAMA. 2016 Sep 27;316(12):1279-88. doi: 10.1001/jama.2016.13647.
• Results Tao C, Nogueira RG, Zhu Y, Sun J, Han H, Yuan G, Wen C, Zhou P, Chen W, Zeng G, Li Y, Ma Z, Yu C, Su J, Zhou Z, Chen Z, Liao G, Sun Y, Ren Y, Zhang H, Chen J, Yue X, Xiao G, Wang L, Liu R, Liu W, Liu Y, Wang L, Zhang C, Liu T, Song J, Li R, Xu P, Yin Y, Wang G, Baxter B, Qureshi AI, Liu X, Hu W; ATTENTION Investigators. Trial of Endovascular Treatment of Acute Basilar-Artery Occlusion. N Engl J Med. 2022 Oct 13;387(15):1361-1372. doi: 10.1056/NEJMoa2206317.
• Results Shi K, Tian DC, Li ZG, Ducruet AF, Lawton MT, Shi FD. Global brain inflammation in stroke. Lancet Neurol. 2019 Nov;18(11):1058-1066. doi: 10.1016/S1474-4422(19)30078-X. Epub 2019 Jul 8.
• Results Yang JL, Yang YR, Chen SD. The potential of drug repurposing combined with reperfusion therapy in cerebral ischemic stroke: A supplementary strategy to endovascular thrombectomy. Life Sci. 2019 Nov 1;236:116889. doi: 10.1016/j.lfs.2019.116889. Epub 2019 Oct 11.
• Results McGarry T, Biniecka M, Veale DJ, Fearon U. Hypoxia, oxidative stress and inflammation. Free Radic Biol Med. 2018 Sep;125:15-24. doi: 10.1016/j.freeradbiomed.2018.03.042. Epub 2018 Mar 27.
• Results Stoll G, Nieswandt B. Thrombo-inflammation in acute ischaemic stroke - implications for treatment. Nat Rev Neurol. 2019 Aug;15(8):473-481. doi: 10.1038/s41582-019-0221-1. Epub 2019 Jul 1.
• Results Kollikowski AM, Schuhmann MK, Nieswandt B, Mullges W, Stoll G, Pham M. Local Leukocyte Invasion during Hyperacute Human Ischemic Stroke. Ann Neurol. 2020 Mar;87(3):466-479. doi: 10.1002/ana.25665. Epub 2020 Jan 16.
• Results El Amki M, Wegener S. Improving Cerebral Blood Flow after Arterial Recanalization: A Novel Therapeutic Strategy in Stroke. Int J Mol Sci. 2017 Dec 9;18(12):2669. doi: 10.3390/ijms18122669.
• Results Bustamante A, Ning M, Garcia-Berrocoso T, Penalba A, Boada C, Simats A, Pagola J, Ribo M, Molina C, Lo E, Montaner J. Usefulness of ADAMTS13 to predict response to recanalization therapies in acute ischemic stroke. Neurology. 2018 Mar 20;90(12):e995-e1004. doi: 10.1212/WNL.0000000000005162. Epub 2018 Feb 14.
• Results Sagris D, Papanikolaou A, Kvernland A, Korompoki E, Frontera JA, Troxel AB, Gavriatopoulou M, Milionis H, Lip GYH, Michel P, Yaghi S, Ntaios G. COVID-19 and ischemic stroke. Eur J Neurol. 2021 Nov;28(11):3826-3836. doi: 10.1111/ene.15008. Epub 2021 Jul 17.
• Results Stein LK, Mayman NA, Dhamoon MS, Fifi JT. The emerging association between COVID-19 and acute stroke. Trends Neurosci. 2021 Jul;44(7):527-537. doi: 10.1016/j.tins.2021.03.005. Epub 2021 Apr 8.
• Results Wichmann D, Sperhake JP, Lutgehetmann M, Steurer S, Edler C, Heinemann A, Heinrich F, Mushumba H, Kniep I, Schroder AS, Burdelski C, de Heer G, Nierhaus A, Frings D, Pfefferle S, Becker H, Bredereke-Wiedling H, de Weerth A, Paschen HR, Sheikhzadeh-Eggers S, Stang A, Schmiedel S, Bokemeyer C, Addo MM, Aepfelbacher M, Puschel K, Kluge S. Autopsy Findings and Venous Thromboembolism in Patients With COVID-19: A Prospective Cohort Study. Ann Intern Med. 2020 Aug 18;173(4):268-277. doi: 10.7326/M20-2003. Epub 2020 May 6.
• Results Hingorani KS, Bhadola S, Cervantes-Arslanian AM. COVID-19 and the brain. Trends Cardiovasc Med. 2022 Aug;32(6):323-330. doi: 10.1016/j.tcm.2022.04.004. Epub 2022 Apr 21.
• Results Cherian R, Tung ML, Chandra B. Severe COVID-19 as a virus-independent immunothrombotic process. Lancet Rheumatol. 2022 Mar;4(3):e172-e173. doi: 10.1016/S2665-9913(22)00033-9. Epub 2022 Feb 24. No abstract available.
• Results Perico L, Benigni A, Casiraghi F, Ng LFP, Renia L, Remuzzi G. Immunity, endothelial injury and complement-induced coagulopathy in COVID-19. Nat Rev Nephrol. 2021 Jan;17(1):46-64. doi: 10.1038/s41581-020-00357-4. Epub 2020 Oct 19.
• Results Jin Z, Liang J, Wang J, Kolattukudy PE. MCP-induced protein 1 mediates the minocycline-induced neuroprotection against cerebral ischemia/reperfusion injury in vitro and in vivo. J Neuroinflammation. 2015 Feb 27;12:39. doi: 10.1186/s12974-015-0264-1.
• Results Tikka T, Fiebich BL, Goldsteins G, Keinanen R, Koistinaho J. Minocycline, a tetracycline derivative, is neuroprotective against excitotoxicity by inhibiting activation and proliferation of microglia. J Neurosci. 2001 Apr 15;21(8):2580-8. doi: 10.1523/JNEUROSCI.21-08-02580.2001.
• Results Sheng Z, Liu Y, Li H, Zheng W, Xia B, Zhang X, Yong VW, Xue M. Efficacy of Minocycline in Acute Ischemic Stroke: A Systematic Review and Meta-Analysis of Rodent and Clinical Studies. Front Neurol. 2018 Dec 20;9:1103. doi: 10.3389/fneur.2018.01103. eCollection 2018.
• Results Switzer JA, Hess DC, Ergul A, Waller JL, Machado LS, Portik-Dobos V, Pettigrew LC, Clark WM, Fagan SC. Matrix metalloproteinase-9 in an exploratory trial of intravenous minocycline for acute ischemic stroke. Stroke. 2011 Sep;42(9):2633-5. doi: 10.1161/STROKEAHA.111.618215. Epub 2011 Jul 7.
• Results Machado LS, Sazonova IY, Kozak A, Wiley DC, El-Remessy AB, Ergul A, Hess DC, Waller JL, Fagan SC. Minocycline and tissue-type plasminogen activator for stroke: assessment of interaction potential. Stroke. 2009 Sep;40(9):3028-33. doi: 10.1161/STROKEAHA.109.556852. Epub 2009 Jul 23.
• Results Naderi Y, Panahi Y, Barreto GE, Sahebkar A. Neuroprotective effects of minocycline on focal cerebral ischemia injury: a systematic review. Neural Regen Res. 2020 May;15(5):773-782. doi: 10.4103/1673-5374.268898.
• Results Fagan SC, Cronic LE, Hess DC. Minocycline development for acute ischemic stroke. Transl Stroke Res. 2011 Jun 1;2(2):202-8. doi: 10.1007/s12975-011-0072-6.
• Results Malhotra K, Chang JJ, Khunger A, Blacker D, Switzer JA, Goyal N, Hernandez AV, Pasupuleti V, Alexandrov AV, Tsivgoulis G. Minocycline for acute stroke treatment: a systematic review and meta-analysis of randomized clinical trials. J Neurol. 2018 Aug;265(8):1871-1879. doi: 10.1007/s00415-018-8935-3. Epub 2018 Jun 14.
• Lu Y, Guan L, Wu J, Yang Q, Zhang M, Zhou D, Yang H, Pan Y, Wang L, Qiu B, Liu C, Wang Y, Yang Y, Zhou X, Qu H, Liao X, Liu L, Zhao X, Bath PM, Johnston SC, Amarenco P, Turc G, Shi FD, Wang Y, Wang Y; EMPHASIS Investigators. Efficacy and safety of minocycline in patients with acute ischaemic stroke (EMPHASIS): a multicentre, double-blind, randomised controlled trial. Lancet. 2026 Feb 14;407(10529):679-688. doi: 10.1016/S0140-6736(25)01862-8. Epub 2026 Jan 30.

Drugs

Indications