Effect of citicoline on functional and cognitive status among patients with traumatic brain injury

Citicoline Brain Injury Treatment Trial (COBRIT)

Ross D. Zafonte, Emilia Bagiella, Beth M. Ansel, Thomas A. Novack, William T. Friedewald, Dale C. Hesdorffer, Shelly Timmons, Jack Jallo, Howard Eisenberg, Tessa Hart, Joseph H. Ricker, Ramon Diaz-Arrastia, Randall E. Merchant, Nancy R. Temkin, Sherry Melton, Sureyya S. Dikmen

Research output: Contribution to journalArticle

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Abstract

Context: 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. Design, Setting, and Patients: 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. Intervention: Ninety-day regimen of daily enteral or oral citicoline (2000 mg) or placebo. Main Outcome Measures: 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 longterm 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]). Conclusion: 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. Trial Registration: clinicaltrials.gov Identifier: NCT00545662.

Original languageEnglish (US)
Pages (from-to)1993-2000
Number of pages8
JournalJAMA - Journal of the American Medical Association
Volume308
Issue number19
DOIs
StatePublished - Nov 21 2012

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Cytidine Diphosphate Choline
Brain Injuries
Placebos
Therapeutics
Odds Ratio
Brain Concussion
Traumatic Brain Injury
Glasgow Outcome Scale
Trauma Centers
Small Intestine
Randomized Controlled Trials
Public Health
Outcome Assessment (Health Care)
Clinical Trials

All Science Journal Classification (ASJC) codes

  • Medicine(all)

Cite this

Zafonte, Ross D. ; Bagiella, Emilia ; Ansel, Beth M. ; Novack, Thomas A. ; Friedewald, William T. ; Hesdorffer, Dale C. ; Timmons, Shelly ; Jallo, Jack ; Eisenberg, Howard ; Hart, Tessa ; Ricker, Joseph H. ; Diaz-Arrastia, Ramon ; Merchant, Randall E. ; Temkin, Nancy R. ; Melton, Sherry ; Dikmen, Sureyya S. / Effect of citicoline on functional and cognitive status among patients with traumatic brain injury : Citicoline Brain Injury Treatment Trial (COBRIT). In: JAMA - Journal of the American Medical Association. 2012 ; Vol. 308, No. 19. pp. 1993-2000.
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title = "Effect of citicoline on functional and cognitive status among patients with traumatic brain injury: Citicoline Brain Injury Treatment Trial (COBRIT)",
abstract = "Context: 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. Design, Setting, and Patients: 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. Intervention: Ninety-day regimen of daily enteral or oral citicoline (2000 mg) or placebo. Main Outcome Measures: 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 longterm 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]). Conclusion: 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. Trial Registration: clinicaltrials.gov Identifier: NCT00545662.",
author = "Zafonte, {Ross D.} and Emilia Bagiella and Ansel, {Beth M.} and Novack, {Thomas A.} and Friedewald, {William T.} and Hesdorffer, {Dale C.} and Shelly Timmons and Jack Jallo and Howard Eisenberg and Tessa Hart and Ricker, {Joseph H.} and Ramon Diaz-Arrastia and Merchant, {Randall E.} and Temkin, {Nancy R.} and Sherry Melton and Dikmen, {Sureyya S.}",
year = "2012",
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doi = "10.1001/jama.2012.13256",
language = "English (US)",
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Zafonte, RD, Bagiella, E, Ansel, BM, Novack, TA, Friedewald, WT, Hesdorffer, DC, Timmons, S, Jallo, J, Eisenberg, H, Hart, T, Ricker, JH, Diaz-Arrastia, R, Merchant, RE, Temkin, NR, Melton, S & Dikmen, SS 2012, 'Effect of citicoline on functional and cognitive status among patients with traumatic brain injury: Citicoline Brain Injury Treatment Trial (COBRIT)', JAMA - Journal of the American Medical Association, vol. 308, no. 19, pp. 1993-2000. https://doi.org/10.1001/jama.2012.13256

Effect of citicoline on functional and cognitive status among patients with traumatic brain injury : Citicoline Brain Injury Treatment Trial (COBRIT). / Zafonte, Ross D.; Bagiella, Emilia; Ansel, Beth M.; Novack, Thomas A.; Friedewald, William T.; Hesdorffer, Dale C.; Timmons, Shelly; Jallo, Jack; Eisenberg, Howard; Hart, Tessa; Ricker, Joseph H.; Diaz-Arrastia, Ramon; Merchant, Randall E.; Temkin, Nancy R.; Melton, Sherry; Dikmen, Sureyya S.

In: JAMA - Journal of the American Medical Association, Vol. 308, No. 19, 21.11.2012, p. 1993-2000.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Effect of citicoline on functional and cognitive status among patients with traumatic brain injury

T2 - Citicoline Brain Injury Treatment Trial (COBRIT)

AU - Zafonte, Ross D.

AU - Bagiella, Emilia

AU - Ansel, Beth M.

AU - Novack, Thomas A.

AU - Friedewald, William T.

AU - Hesdorffer, Dale C.

AU - Timmons, Shelly

AU - Jallo, Jack

AU - Eisenberg, Howard

AU - Hart, Tessa

AU - Ricker, Joseph H.

AU - Diaz-Arrastia, Ramon

AU - Merchant, Randall E.

AU - Temkin, Nancy R.

AU - Melton, Sherry

AU - Dikmen, Sureyya S.

PY - 2012/11/21

Y1 - 2012/11/21

N2 - Context: 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. Design, Setting, and Patients: 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. Intervention: Ninety-day regimen of daily enteral or oral citicoline (2000 mg) or placebo. Main Outcome Measures: 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 longterm 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]). Conclusion: 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. Trial Registration: clinicaltrials.gov Identifier: NCT00545662.

AB - Context: 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. Design, Setting, and Patients: 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. Intervention: Ninety-day regimen of daily enteral or oral citicoline (2000 mg) or placebo. Main Outcome Measures: 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 longterm 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]). Conclusion: 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. Trial Registration: clinicaltrials.gov Identifier: NCT00545662.

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