Efficacy and Safety of Minocycline in Acute Spontaneous Intracerebral Hemorrhage

Summary

This is a prospective, multicenter, randomized, double-blind, placebo-controlled clinical trial. It aims to evaluate the efficacy and safety of oral minocycline in patients with acute spontaneous intracerebral hemorrhage within 48 hours of onset.

Timeline

Start

2026-04-02

Primary completion

2028-06

Completion

2028-12

Publications

• Results Chang JJ, Kim-Tenser M, Emanuel BA, Jones GM, Chapple K, Alikhani A, Sanossian N, Mack WJ, Tsivgoulis G, Alexandrov AV, Pourmotabbed T. Minocycline and matrix metalloproteinase inhibition in acute intracerebral hemorrhage: a pilot study. Eur J Neurol. 2017 Nov;24(11):1384-1391. doi: 10.1111/ene.13403. Epub 2017 Sep 20.
• Results Lu Y, Guan L, Zhang M, Yang Q, Qiu B, Zhou D, Wang Y, Pan Y, Wang L, Zhou X, Qu H, Liao X, Liu L, Zhao X, Bath PM, Johnston SC, Amarenco P, Wang Y, Wang Y. Rationale and Study Design to Assess the Efficacy and Safety of Minocycline in Patients with Moderate to Severe Acute Ischaemic Stroke (EMPHASIS). Stroke Vasc Neurol. 2025 Dec 23;10(6):786-792. doi: 10.1136/svn-2024-003577.
• Results Fouda AY, Newsome AS, Spellicy S, Waller JL, Zhi W, Hess DC, Ergul A, Edwards DJ, Fagan SC, Switzer JA. Minocycline in Acute Cerebral Hemorrhage: An Early Phase Randomized Trial. Stroke. 2017 Oct;48(10):2885-2887. doi: 10.1161/STROKEAHA.117.018658. Epub 2017 Sep 8.
• Results 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.
• Results Wu DC, Jackson-Lewis V, Vila M, Tieu K, Teismann P, Vadseth C, Choi DK, Ischiropoulos H, Przedborski S. Blockade of microglial activation is neuroprotective in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine mouse model of Parkinson disease. J Neurosci. 2002 Mar 1;22(5):1763-71. doi: 10.1523/JNEUROSCI.22-05-01763.2002.
• Results Kraus RL, Pasieczny R, Lariosa-Willingham K, Turner MS, Jiang A, Trauger JW. Antioxidant properties of minocycline: neuroprotection in an oxidative stress assay and direct radical-scavenging activity. J Neurochem. 2005 Aug;94(3):819-27. doi: 10.1111/j.1471-4159.2005.03219.x.
• Results Lee JM, Yin K, Hsin I, Chen S, Fryer JD, Holtzman DM, Hsu CY, Xu J. Matrix metalloproteinase-9 in cerebral-amyloid-angiopathy-related hemorrhage. J Neurol Sci. 2005 Mar 15;229-230:249-54. doi: 10.1016/j.jns.2004.11.041. Epub 2004 Dec 29.
• Results Yrjanheikki J, Tikka T, Keinanen R, Goldsteins G, Chan PH, Koistinaho J. A tetracycline derivative, minocycline, reduces inflammation and protects against focal cerebral ischemia with a wide therapeutic window. Proc Natl Acad Sci U S A. 1999 Nov 9;96(23):13496-500. doi: 10.1073/pnas.96.23.13496.
• Results Garrido-Mesa N, Zarzuelo A, Galvez J. What is behind the non-antibiotic properties of minocycline? Pharmacol Res. 2013 Jan;67(1):18-30. doi: 10.1016/j.phrs.2012.10.006. Epub 2012 Oct 17.
• Results Fu Y, Hao J, Zhang N, Ren L, Sun N, Li YJ, Yan Y, Huang D, Yu C, Shi FD. Fingolimod for the treatment of intracerebral hemorrhage: a 2-arm proof-of-concept study. JAMA Neurol. 2014 Sep;71(9):1092-101. doi: 10.1001/jamaneurol.2014.1065.
• Results Xue M, Yong VW. Neuroinflammation in intracerebral haemorrhage: immunotherapies with potential for translation. Lancet Neurol. 2020 Dec;19(12):1023-1032. doi: 10.1016/S1474-4422(20)30364-1.
• Results Bai Q, Xue M, Yong VW. Microglia and macrophage phenotypes in intracerebral haemorrhage injury: therapeutic opportunities. Brain. 2020 May 1;143(5):1297-1314. doi: 10.1093/brain/awz393.
• Results Puy L, Perbet R, Figeac M, Duchene B, Deramecourt V, Cordonnier C, Berezowski V. Brain Peri-Hematomal Area, a Strategic Interface for Blood Clearance: A Human Neuropathological and Transcriptomic Study. Stroke. 2022 Jun;53(6):2026-2035. doi: 10.1161/STROKEAHA.121.037751. Epub 2022 Apr 25.
• Results Li N, Guo J, Kang K, Zhang J, Zhang Z, Liu L, Liu X, Du Y, Wang Y, Zhao X. Cytotoxic Edema and Adverse Clinical Outcomes in Patients with Intracerebral Hemorrhage. Neurocrit Care. 2023 Apr;38(2):414-421. doi: 10.1007/s12028-022-01603-2. Epub 2022 Sep 30.
• Results Cordonnier C, Demchuk A, Ziai W, Anderson CS. Intracerebral haemorrhage: current approaches to acute management. Lancet. 2018 Oct 6;392(10154):1257-1268. doi: 10.1016/S0140-6736(18)31878-6.
• Results Greenberg SM, Ziai WC, Cordonnier C, Dowlatshahi D, Francis B, Goldstein JN, Hemphill JC 3rd, Johnson R, Keigher KM, Mack WJ, Mocco J, Newton EJ, Ruff IM, Sansing LH, Schulman S, Selim MH, Sheth KN, Sprigg N, Sunnerhagen KS; American Heart Association/American Stroke Association. 2022 Guideline for the Management of Patients With Spontaneous Intracerebral Hemorrhage: A Guideline From the American Heart Association/American Stroke Association. Stroke. 2022 Jul;53(7):e282-e361. doi: 10.1161/STR.0000000000000407. Epub 2022 May 17. No abstract available.
• Results Wu TY, Sharma G, Strbian D, Putaala J, Desmond PM, Tatlisumak T, Davis SM, Meretoja A. Natural History of Perihematomal Edema and Impact on Outcome After Intracerebral Hemorrhage. Stroke. 2017 Apr;48(4):873-879. doi: 10.1161/STROKEAHA.116.014416. Epub 2017 Mar 8.
• Results Murthy SB, Moradiya Y, Dawson J, Lees KR, Hanley DF, Ziai WC; VISTA-ICH Collaborators. Perihematomal Edema and Functional Outcomes in Intracerebral Hemorrhage: Influence of Hematoma Volume and Location. Stroke. 2015 Nov;46(11):3088-92. doi: 10.1161/STROKEAHA.115.010054. Epub 2015 Sep 22.
• Results Sheth KN. Spontaneous Intracerebral Hemorrhage. N Engl J Med. 2022 Oct 27;387(17):1589-1596. doi: 10.1056/NEJMra2201449. No abstract available.
• Results Gross BA, Jankowitz BT, Friedlander RM. Cerebral Intraparenchymal Hemorrhage: A Review. JAMA. 2019 Apr 2;321(13):1295-1303. doi: 10.1001/jama.2019.2413.
• Results Wang WJ, Lu JJ, Wang YJ, Wang CX, Wang YL, Hoff K, Yang ZH, Liu LP, Wang AX, Zhao XQ; China National Stroke Registry (CNSR). Clinical characteristics, management, and functional outcomes in Chinese patients within the first year after intracerebral hemorrhage: analysis from China National Stroke Registry. CNS Neurosci Ther. 2012 Sep;18(9):773-80. doi: 10.1111/j.1755-5949.2012.00367.x.
• Results Flower O, Smith M. The acute management of intracerebral hemorrhage. Curr Opin Crit Care. 2011 Apr;17(2):106-14. doi: 10.1097/MCC.0b013e328342f823.
• Results Zhao Y, Hua X, Ren X, Ouyang M, Chen C, Li Y, Yin X, Song P, Chen X, Wu S, Song L, Anderson CS. Increasing burden of stroke in China: A systematic review and meta-analysis of prevalence, incidence, mortality, and case fatality. Int J Stroke. 2023 Mar;18(3):259-267. doi: 10.1177/17474930221135983. Epub 2022 Nov 16.
• Results Ma Q, Li R, Wang L, Yin P, Wang Y, Yan C, Ren Y, Qian Z, Vaughn MG, McMillin SE, Hay SI, Naghavi M, Cai M, Wang C, Zhang Z, Zhou M, Lin H, Yang Y. Temporal trend and attributable risk factors of stroke burden in China, 1990-2019: an analysis for the Global Burden of Disease Study 2019. Lancet Public Health. 2021 Dec;6(12):e897-e906. doi: 10.1016/S2468-2667(21)00228-0.
• 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.

Drugs

Indications