{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,9]],"date-time":"2026-11-09T23:30:22Z","timestamp":1794267022851,"version":"4.9.0"},"reference-count":49,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2025,12,12]],"date-time":"2025-12-12T00:00:00Z","timestamp":1765497600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2025,12,12]],"date-time":"2025-12-12T00:00:00Z","timestamp":1765497600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sig Transduct Target Ther"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    To assess the efficacy and safety of L-oxiracetam, a novel nootropic agent, in improving cognition in patients with TBI, we performed a multicentre, double-blind, randomized controlled trial in China. Participants aged 18 to 75 years with TBI (Glasgow Coma Scale score of 10 to 15) were recruited from 51 hospitals from 2019 to 2024. Patients were randomly assigned to L-oxiracetam, 4\u2009g\/day, oxiracetam 6\u2009g\/day, or placebo in 2:2:1. The primary outcome was the change in the Loewenstein Occupational Therapy Cognitive Assessment (LOTCA) score from baseline to 90 days post treatment. Secondary outcomes included changes in additional cognitive evaluations, neurological function, activities of daily living (ADL), and adverse events (AEs). The trial was approved by the China National Medical Products Administration (2016L03521), and registered at Clinicaltrials.gov (NCT04205565) and Chinadrugtrials.org.cn (CTR20192539). Five hundred and ninety patients were included (mean age (SD), 50.9 (14.5); 421 males). The least squares (LS) mean of LOTCA change from baseline to 90 days post treatment was 20.45 (95% confidence interval [CI] 17.23, 23.66) in the L-oxiracetam group, 15.90 (95% CI 12.71, 19.10) in the oxiracetam group, and 11.47 (95% CI 7.75, 15.20) in the placebo group (\n                    <jats:italic>P<\/jats:italic>\n                    value\u2009&lt;\u20090.05 for all groups). The LS mean difference of the L-oxiracetam was significantly higher than the placebo group (8.97, 95% CI 5.69,12.26;\n                    <jats:italic>P<\/jats:italic>\n                    \u2009&lt;\u20090.001; Cohen\u2019s\n                    <jats:italic>d<\/jats:italic>\n                    \u2009=\u20090.48 [95% CI: 0.26,0.69]) and the oxiracetam group (4.54, 95% CI 1.85,7.23). Secondary efficacy outcomes did not differ between the L-oxiracetam and oxiracetam groups. The proportion of serious AEs did not differ among the three groups. L-oxiracetam could improve cognitive function in patients with mild-to-moderate TBI. L-oxiracetam might be more efficacious than oxiracetam. No significant safety concerns were reported. Despite limitations such as loss to follow-up, the findings of this study provide important evidence for the clinical management of cognitive dysfunction following TBI. Future studies in real-world clinical settings are warranted to further substantiate the efficacy of L-oxiracetam and oxiracetam.\n                  <\/jats:p>","DOI":"10.1038\/s41392-025-02492-5","type":"journal-article","created":{"date-parts":[[2025,12,12]],"date-time":"2025-12-12T00:02:05Z","timestamp":1765497725000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Efficacy and safety of L-oxiracetam on cognitive function in patients with traumatic brain injury: a multicentre, randomised, double-blind, phase 3 clinical 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