Methylprednisolone for Moderate to Severe Traumatic Brain Injury

Summary

The goal of this clinical trial is to learn if standard-dose methylprednisolone sodium succinate can improve neurological recovery and safety in adults with moderate to severe traumatic brain injury (TBI). The main questions it aims to answer are: 1. Does adding a 5-day course of methylprednisolone improve overall long-term neurological outcome compared with placebo? 2. Does methylprednisolone reduce 6-month mortality or increase the proportion of patients with good neurological recovery? 3. What medical problems do participants experience when receiving methylprednisolone? Researchers will compare methylprednisolone sodium succinate (2 mg/kg/day intravenously for 5 days) with a matching placebo to see if the steroid improves outcomes beyond standard TBI care. Participants will: 1. Receive either methylprednisolone or placebo once daily for 5 days, added to guideline-directed standard care. 2. Undergo CT scans and neuro-examinations during hospitalization. 3. Return for follow-up visits at 1 month and 6 months after injury for neurological assessments, safety checks, and questionnaires.

Timeline

Start

2025-10-01

Primary completion

2027-10-01

Completion

2028-03-01

Publications

• Background Carney N, Totten AM, O'Reilly C, Ullman JS, Hawryluk GW, Bell MJ, Bratton SL, Chesnut R, Harris OA, Kissoon N, Rubiano AM, Shutter L, Tasker RC, Vavilala MS, Wilberger J, Wright DW, Ghajar J. Guidelines for the Management of Severe Traumatic Brain Injury, Fourth Edition. Neurosurgery. 2017 Jan 1;80(1):6-15. doi: 10.1227/NEU.0000000000001432.
• Background Roberts I, Yates D, Sandercock P, Farrell B, Wasserberg J, Lomas G, Cottingham R, Svoboda P, Brayley N, Mazairac G, Laloe V, Munoz-Sanchez A, Arango M, Hartzenberg B, Khamis H, Yutthakasemsunt S, Komolafe E, Olldashi F, Yadav Y, Murillo-Cabezas F, Shakur H, Edwards P; CRASH trial collaborators. Effect of intravenous corticosteroids on death within 14 days in 10008 adults with clinically significant head injury (MRC CRASH trial): randomised placebo-controlled trial. Lancet. 2004 Oct 9-15;364(9442):1321-8. doi: 10.1016/S0140-6736(04)17188-2.
• Background He C, Wang Y, Gong W, Zhang S. Targeted Delivery of Acid-Responsive Rutin Nanoparticles Based on Aldehyde Adsorption for the Treatment of Spinal Cord Injury in Rats. ACS Biomater Sci Eng. 2025 Apr 14;11(4):2192-2202. doi: 10.1021/acsbiomaterials.5c00038. Epub 2025 Apr 1.
• Background Chen X, Chai Y, Wang SB, Wang JC, Yue SY, Jiang RC, Zhang JN. Risk factors for corticosteroid insufficiency during the sub-acute phase of acute traumatic brain injury. Neural Regen Res. 2020 Jul;15(7):1259-1265. doi: 10.4103/1673-5374.272611.
• Background Zhang B, Bai M, Xu X, Yang M, Niu F, Gao F, Liu B. Corticosteroid receptor rebalancing alleviates critical illness-related corticosteroid insufficiency after traumatic brain injury by promoting paraventricular nuclear cell survival via Akt/CREB/BDNF signaling. J Neuroinflammation. 2020 Oct 25;17(1):318. doi: 10.1186/s12974-020-02000-2.
• Background Liu Z, Yang Y, He L, Pang M, Luo C, Liu B, Rong L. High-dose methylprednisolone for acute traumatic spinal cord injury: A meta-analysis. Neurology. 2019 Aug 27;93(9):e841-e850. doi: 10.1212/WNL.0000000000007998. Epub 2019 Jul 29.
• Background Zhang Y, Xiao S, Zhu L, Gan X, Huang Y, Dan F, Chen J, Zhou R, Tang W, Liu J, Liu Z. Effect of Low-dose Methylprednisolone in Promoting Neurological Function Recovery After Spinal Cord Injury: Clinical and Animal Studies. Spine (Phila Pa 1976). 2025 Jul 15;50(14):965-974. doi: 10.1097/BRS.0000000000005269. Epub 2025 Jan 29.
• Background Zheng C, Li R, Shen C, Guo F, Fan D, Yang L, Zhang L, Chen A, Chen Y, Chen D, Zi W, Guo C, Nguyen TN, Albers GW, Campbell BCV, Qiu Z, Hu Z. Methylprednisolone as Adjunct to Thrombectomy for Acute Intracranial Internal Carotid Artery Occlusion Stroke: Post Hoc Secondary Analysis of the MARVEL Randomized Clinical Trial. JAMA Netw Open. 2025 Feb 3;8(2):e2459945. doi: 10.1001/jamanetworkopen.2024.59945.
• Background Wang B, Zhang Q, Liu C, Chen X. Counteracting immunodepression by extracellular matrix hydrogel to promote brain tissue remodeling and neurological function recovery after traumatic brain injury. Biomaterials. 2025 Jul;318:123181. doi: 10.1016/j.biomaterials.2025.123181. Epub 2025 Feb 8.

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