Study of Citicoline for the Treatment of Traumatic Brain Injury (COBRIT)

This study has been terminated.
(Trial stopped due to futility.)
Sponsor:
Information provided by (Responsible Party):
William Friedewald, Columbia University
ClinicalTrials.gov Identifier:
NCT00545662
First received: October 16, 2007
Last updated: November 16, 2012
Last verified: November 2012
Results First Received: November 29, 2011  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Efficacy Study;   Intervention Model: Parallel Assignment;   Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition: Traumatic Brain Injury
Interventions: Drug: Placebo
Drug: citicoline

  Participant Flow
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Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
Participant were recruited from eight level I trauma centers: Virginia Commonwealth University; University of Maryland; Temple University; University of Tennessee; University of Alabama (Birmingham); University of Texas Southwestern (Dallas); University of Pittsburgh; University of Washington. Recruitment began on 7/23/2007 and ended on 2/4/2011.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
None.

Reporting Groups
  Description
Control The first dose of placebo was administered within 24 hours of traumatic brain injury. Placebo was administered orally or enterally depending upon whether the participant could swallow at 1,000 mg twice a day for 90 days or until the 90-day outcome assessment.
Treatment Treatment with citicoline begun within 24 hours of traumatic brain injury. Treatment was administered orally or enterally depending upon whether the participant could swallow at 1,000 mg twice a day for 90 days or until the 90-day outcome assessment.

Participant Flow:   Overall Study
    Control     Treatment  
STARTED     606     607  
COMPLETED     521     528  
NOT COMPLETED     85     79  



  Baseline Characteristics
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Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
No text entered.

Reporting Groups
  Description
Control The first dose of placebo was administered within 24 hours of traumatic brain injury. Placebo was administered orally or enterally depending upon whether the participant could swallow at 1,000 mg twice a day for 90 days or until the 90-day outcome assessment.
Treatment Treatment with citicoline begun within 24 hours of traumatic brain injury. Treatment was administered orally or enterally depending upon whether the participant could swallow at 1,000 mg twice a day for 90 days or until the 90-day outcome assessment.
Total Total of all reporting groups

Baseline Measures
    Control     Treatment     Total  
Number of Participants  
[units: participants]
  606     607     1213  
Age  
[units: participants]
     
<=18 years     0     1     1  
Between 18 and 65 years     568     563     1131  
>=65 years     38     43     81  
Age  
[units: years]
Mean ± Standard Deviation
  41.1  ± 15.5     39.7  ± 16.2     40.4  ± 15.9  
Gender  
[units: participants]
     
Female     159     151     310  
Male     447     456     903  
Region of Enrollment  
[units: participants]
     
United States     606     607     1213  



  Outcome Measures

1.  Primary:   Functional and Cognitive Outcome   [ Time Frame: 90 days ]
  Hide Outcome Measure 1

Measure Type Primary
Measure Title Functional and Cognitive Outcome
Measure Description The primary outcome of this study was analyzed using a global statistic of the Network Core Battery. There were 9 scales: California Verbal Learning Test II (CVLT-II); Controlled Oral Word Association Test (COWAT); Digit Span (DS); Glasgow Outcome Scale Extended (GOSE); Processing Speed Index (PSI); Stroop Test 1 and 2 (ST1&2); and Trail Making Test part A and B (TMT parts A and B). Each scale was assigned cut-off for good outcome: GOSE>7, CVLT>36, PSI>85, TMT part A <42, TMT part B<138.1, DS>7.15, ST1<60.29, ST2<151.47, COWAT>32.5. Logistic regression was used to estimate the global OR.
Time Frame 90 days  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The analysis included both the patients with complete outcome data and those with at least one measure. Patients who died were also included in the analysis.

Reporting Groups
  Description
Control The first dose of placebo was administered within 24 hours of traumatic brain injury. Placebo was administered orally or enterally depending upon whether the participant could swallow at 1,000 mg twice a day for 90 days or until the 90-day outcome assessment.
Treatment Treatment with citicoline begun within 24 hours of traumatic brain injury. Treatment was administered orally or enterally depending upon whether the participant could swallow at 1,000 mg twice a day for 90 days or until the 90-day outcome assessment.

Measured Values
    Control     Treatment  
Number of Participants Analyzed  
[units: participants]
  509     508  
Functional and Cognitive Outcome  
[units: percentage¬†of¬†participants]
   
Glasgow Outcome Scale - Extended     35.56     35.43  
California Verbal Learning Test     60.48     57.71  
Processing Speed Index     53.28     52.68  
Trail Making A     61.96     64.96  
Trail Making B     71.05     74.44  
Digit Span     84.02     86.50  
Stroop Task 1     67.95     65.31  
Stroop Task 2     66.59     68.29  
Controlled Oral Word Association Test     42.68     37.32  


Statistical Analysis 1 for Functional and Cognitive Outcome
Groups [1] All groups
Method [2] Regression, Logistic
P Value [3] 0.76
Odds Ratio (OR) [4] 0.98
95% Confidence Interval ( 0.83 to 1.14 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
 

Null hypothesis: The placebo and citicoline groups do not differ at 90-days on the Core Battery

Power:

  1. Two sided type I error of 0.05
  2. 85% power
  3. Expected OR=1.40 for the global statistic
  4. Response rate in the control group
  5. Correlations among the nine measures were accounted for. Response rates for the whole sample were a weighted average of the rates provided by TBI severity.

1240 participants were required to detect an OR >= 1.4 for the global statistic.

[2] Other relevant method information, such as adjustments or degrees of freedom:
  Logistic regression estimated global OR. GEE accounted for correlations of the scales. Models adjusted for site & injury severity.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  a priori threshold for statistical significance is 0.05
[4] Other relevant estimation information:
  The odds in the citicoline group were compared to the odds in the placebo group.




  Serious Adverse Events


  Other Adverse Events


  More Information
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Certain Agreements:  
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.


Limitations and Caveats
Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
No text entered.  


Results Point of Contact:  
Name/Title: Dr. William Friedewald
Organization: Columbia University
phone: 212-305-3017
e-mail: wtf1@columbia.edu


No publications provided by Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

Publications automatically indexed to this study:

Responsible Party: William Friedewald, Columbia University
ClinicalTrials.gov Identifier: NCT00545662     History of Changes
Other Study ID Numbers: BA-HD042, HD042687-04, HD042738-05, HD042678-03, HD042653-05, HD042689-05, HD042736-04, HD 042686-01A1, HD042652-04, HD042823-05
Study First Received: October 16, 2007
Results First Received: November 29, 2011
Last Updated: November 16, 2012
Health Authority: United States: Food and Drug Administration