Citicoline for Treatment of Head Trauma. Systematic Review and Meta-analysis of Clinical Controlled Trials

Trabajos Distinguidos Neurología 01/2013; 3:4.

ABSTRACT Background: Citicoline is a neuroprotective/neurorestorative drug used in several countries for the
treatment of traumatic brain injury. After the publication of the controversial COBRIT trial, the use of
citicoline has been questioned in this use, then it has been considered as necessary proceed to do a
systematic review to evaluate if citicoline is effective in the treatment of patients with traumatic brain
injury. Methods: A systematic search was performed on Medline, Embase, and Ferrer Group database to
identify all published, unconfounded, comparative clinical trials of citicoline in acute phase head injured
patients. Results: 12 controlled trials enrolling 2 706 patients were identified. Under the random-effects
model, the meta-analysis shows an 1.815 (IC 95:% 1.302-2.530) in favour of citicoline in the rates of
independence, using as measure the Galsgow Outcome Scale. The effect of citicoline has been diluted
across the time in parallel with the improvement of the standard of care of this kind of pacients, as demonstrated
by the cumulative meta-analysis technique. Conclusion: Formal meta-analysis of comparative
trials of citicoline in traumatic brain injury shows a beneficial treatment effect, without safety concerns.

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    ABSTRACT: Traumatic brain injury (TBI) is a serious public health problem in the United States, yet no treatment is currently available to improve outcome after TBI. Approved for use in TBI in 59 countries, citicoline is an endogenous substance offering potential neuroprotective properties as well as facilitated neurorepair post injury. To determine the ability of citicoline to positively affect functional and cognitive status in persons with complicated mild, moderate, and severe TBI. The Citicoline Brain Injury Treatment Trial (COBRIT), a phase 3, double-blind randomized clinical trial conducted between July 20, 2007, and February 4, 2011, among 1213 patients at 8 US level 1 trauma centers to investigate effects of citicoline vs placebo in patients with TBI classified as complicated mild, moderate, or severe. Ninety-day regimen of daily enteral or oral citicoline (2000 mg) or placebo. Functional and cognitive status, assessed at 90 days using the TBI-Clinical Trials Network Core Battery. A global statistical test was used to analyze the 9 scales of the core battery. Secondary outcomes were functional and cognitive improvement, assessed at 30, 90, and 180 days, and examination of the long-term maintenance of treatment effects. Rates of favorable improvement for the Glasgow Outcome Scale-Extended were 35.4% in the citicoline group and 35.6% in the placebo group. For all other scales the rate of improvement ranged from 37.3% to 86.5% in the citicoline group and from 42.7% to 84.0% in the placebo group. The citicoline and placebo groups did not differ significantly at the 90-day evaluation (global odds ratio [OR], 0.98 [95% CI, 0.83-1.15]); in addition, there was no significant treatment effect in the 2 severity subgroups (global OR, 1.14 [95% CI, 0.88-1.49] and 0.89 [95% CI, 0.72-1.49] for moderate/severe and complicated mild TBI, respectively). At the 180-day evaluation, the citicoline and placebo groups did not differ significantly with respect to the primary outcome (global OR, 0.87 [95% CI, 0.72-1.04]). Among patients with traumatic brain injury, the use of citicoline compared with placebo for 90 days did not result in improvement in functional and cognitive status. Identifier: NCT00545662.
    JAMA The Journal of the American Medical Association 11/2012; 308(19):1993-2000. DOI:10.1001/jama.2012.13256 · 30.39 Impact Factor
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    ABSTRACT: Cerebral ischemia leads to brain damage caused by pathogenetic mechanisms that are also activated by neurotrauma. These mechanisms include among others excitotoxicity, over production of free radicals, inflammation and apoptosis. Furthermore, cerebral ischemia and trauma both trigger similar auto-protective mechanisms including the production of heat shock proteins, anti-inflammatory cytokines and endogenous antioxidants. Neuroprotective therapy aims at minimizing the activation of toxic pathways and at enhancing the activity of endogenous neuroprotective mechanisms. The similarities in the damage-producing and endogenous auto-protective mechanisms may imply that neuroprotective compounds found to be active against one of these conditions may indeed be also protective in the other. This review summarizes the pathogenetic events of ischemic and traumatic brain injury and reviews the neuroprotective strategies employed thus far in each of these conditions with a special emphasize on their clinical relevance and on future directions in the field of neuronal protection.
    Brain Research Reviews 07/2002; 39(1):55-73. DOI:10.1016/S0165-0173(02)00157-1 · 5.93 Impact Factor
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