title: Effect of citicoline on functional and cognitive status among patients with traumatic brain injury: Citicoline Brain Injury Treatment Trial (COBRIT).
abstract: BACKGROUND
  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.
  
  
  OBJECTIVE
  To determine the ability of citicoline to positively affect functional and cognitive status in persons with complicated mild, moderate, and severe TBI.
  
  
  METHODS
  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.
  
  
  METHODS
  Ninety-day regimen of daily enteral or oral citicoline (2000 mg) or placebo.
  
  
  METHODS
  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.
  
  
  RESULTS
  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]).
  
  
  CONCLUSIONS
  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.
  
  
  BACKGROUND
  clinicaltrials.gov Identifier: NCT00545662.
authors.affiliation: Department of Physical Medicine and Rehabilitation, Harvard Medical School, and Massachusetts General Hospital, Boston, Massachusetts 02114, USA. rzafonte@partners.org
authors.forename: Ross D
authors.initials: RD
authors.lastname: Zafonte
authors.forename: Emilia
authors.initials: E
authors.lastname: Bagiella
authors.forename: Beth M
authors.initials: BM
authors.lastname: Ansel
authors.forename: Thomas A
authors.initials: TA
authors.lastname: Novack
authors.forename: William T
authors.initials: WT
authors.lastname: Friedewald
authors.forename: Dale C
authors.initials: DC
authors.lastname: Hesdorffer
authors.forename: Shelly D
authors.initials: SD
authors.lastname: Timmons
authors.forename: Jack
authors.initials: J
authors.lastname: Jallo
authors.forename: Howard
authors.initials: H
authors.lastname: Eisenberg
authors.forename: Tessa
authors.initials: T
authors.lastname: Hart
authors.forename: Joseph H
authors.initials: JH
authors.lastname: Ricker
authors.forename: Ramon
authors.initials: R
authors.lastname: Diaz-Arrastia
authors.forename: Randall E
authors.initials: RE
authors.lastname: Merchant
authors.forename: Nancy R
authors.initials: NR
authors.lastname: Temkin
authors.forename: Sherry
authors.initials: S
authors.lastname: Melton
authors.forename: Sureyya S
authors.initials: SS
authors.lastname: Dikmen
mesh_terms: D000293:Adolescent; D000328:Adult; D001930:Brain Injuries / Q000150:complications / Q000188:drug therapy*; D003072:Cognition Disorders / Q000150:complications / Q000188:drug therapy*; D003566:Cytidine Diphosphate Choline / Q000627:therapeutic use*; D004311:Double-Blind Method; D005260:Female; D015600:Glasgow Coma Scale; D006801:Humans; D008297:Male; D008875:Middle Aged; D018697:Nootropic Agents / Q000627:therapeutic use*; D012720:Severity of Illness Index; D014193:Trauma Centers; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D018697:Nootropic Agents; D003566:Cytidine Diphosphate Choline