Oxiracetam

Findings:

This text describes a study protocol; findings from this specific Phase III trial are not reported. The abstract notes a current lack of robust evidence for the efficacy of l-oxiracetam or oxiracetam in TBI patients. Preliminary results from a previous Phase II trial are mentioned, suggesting l-oxiracetam (4 g/day) showed a statistically significant improvement in LOTCA scores compared to placebo at 3 months post-treatment.

Participants:

N=590 patients aged 18–75 years with mild-to-moderate traumatic brain injury (TBI) meeting specific criteria: clear evidence of head trauma, confirmed intracranial bleeding via MRI/CT, Glasgow Coma Scale (GCS) 9–15, stable condition within 72h post-injury, undergoing conservative treatment, MMSE score below normal adjusted for education level. Recruited from 74 centers across 51 hospitals in China.

Dosage:

Injectable l-oxiracetam (4 g/day), injectable oxiracetam (6 g/day), or placebo administered for 14 days using a double-blind, double-dummy method.

Study Quality Assessment:

Study protocol for a multicenter (74 centers, 51 hospitals in China), randomized, double-blind, parallel-group, placebo-controlled, three-arm, phase III clinical trial. Registered (chinadrugtrials.org.cn identifier CTR20192539; ClinicalTrials.gov identifier NCT04205565). Adheres to Helsinki Declaration, approved by ethics committees and China National Medical Products Administration. Sample size N=590 (236 l-oxiracetam, 236 oxiracetam, 118 placebo) calculated using PASS software based on pilot trial data, accounting for 15% dropout. Centralized block randomization (2:2:1 ratio) via IWRS. Double-blind, double-dummy design with placebo controls; specific research nurses for drug dispensing. Statistical analysis plan detailed (ITT principle, ANCOVA, SAS 9.4). Data management via eCRF following GCP, audits planned. Acknowledged potential limitations: predominantly Chinese sample, sample collection timing constraints, dose ratio assessment standard. Funding acknowledged (Nanjing Yoko Pharmaceutical Co., Ltd.) with statement of no funder involvement in study design, data handling, or publication decisions.

Findings:

Supplementation with vitamins B12, B6, or folic acid, alone or in combination, did not improve cognitive function (across various domains) in older adults, regardless of whether they had pre-existing cognitive impairment. B-vitamin supplementation did statistically significantly lower total homocysteine levels compared to placebo.

Participants:

Older adults (50 years or older), with or without cognitive impairment (Alzheimer's disease, dementia, or mild cognitive impairment) or dementia. Some participants were volunteers without cognitive impairment; some had other health conditions such as hypertension and cerebrovascular disease. Total N=5,398 across 19 RCTs.

Dosage:

Doses varied across trials: folic acid from 0.75mg to 15mg, vitamin B12 from 0.05mg to 1mg, and vitamin B6 from 3mg to 50mg. Duration ranged from 4 weeks to 5.4 years.

Study Quality Assessment:

Systematic review and meta-analysis of randomised placebo controlled trials (RCTs). Trial quality assessed using criteria (random allocation, allocation concealment, blinding, incomplete outcome data, selective reporting, other bias); 6/19 RCTs met all criteria. Potential limitations mentioned: language bias (English only search), single reviewer for data extraction, unclear if quality assessment done in duplicate (potential reviewer error/bias), considerable clinical and methodological heterogeneity between trials, small sample sizes in some trials, short treatment durations in some trials, uncertainties regarding adequate power. Publication bias assessed using funnel plots (no evidence found).

All Effects: