Efficacy and safety of oxiracetam for cognitive and functional outcomes after acute traumatic brain injury in Chinese populations: a systematic review and meta-analysis of randomized controlled trials

Background Oxiracetam is used in China for cognitive dysfunction after traumatic brain injury (TBI), but its efficacy and safety remain uncertain. We assessed oxiracetam in adults with acute TBI. Methods We searched six bibliographic databases and trial registries from inception through 28 February 2026, for randomized trials. Risk of bias was assessed with the Cochrane risk-of-bias tool (RoB 1), and evidence certainty with GRADE. We performed comparator-stratified random-effects meta-analyses and verified treatment regimens, assessment times, and numerical data against source reports. Results Thirty-three randomized controlled trials involving 2,864 participants contributed to the quantitative synthesis. When both groups received the same or otherwise balanced background therapy, mean post-treatment MMSE scores were 4.67 points higher with oxiracetam (10 studies, n = 798; MD 4.67, 95% CI 3.07–6.28; I 2 = 92%), and NIHSS scores were 3.22 points lower (8 studies, n = 685; MD −3.22, 95% CI −4.14 to −2.30; I 2 = 58%). Compared with piracetam, mean post-treatment MMSE scores were 4.05 points higher with oxiracetam (8 studies, n = 739; MD 4.05, 95% CI 3.51–4.60; I 2 = 0%). These MDs were between-group differences in endpoint scores, not within-patient changes. Barthel Index and GCS scores were also higher with oxiracetam in balanced-background comparisons, but heterogeneity was substantial. More participants met study-defined response criteria with oxiracetam than with control (5 studies, n = 558; RR 1.26, 95% CI 1.16–1.37; I 2 = 0%). In balanced-background comparisons, reported adverse events or adverse reactions did not differ significantly between groups (5 studies, n = 504; RR 1.14, 95% CI 0.64–2.04; I 2 = 0%), although reporting was sparse and incomplete. Conclusion Oxiracetam was associated with higher short-term MMSE scores and, in some comparisons, lower NIHSS scores and higher Barthel Index and GCS scores after acute TBI. Risk of bias, clinical heterogeneity, variable assessment timing, incomplete safety reporting, and low or very low certainty of evidence preclude firm conclusions about durable benefit or routine clinical use. Systematic Review Registration https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD420261394733 , identifier CRD420261394733.