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

Phase 3

Terminated

• Conditions: Traumatic Brain Injury
• Interventions: Drug: Placebo; Drug: citicoline

• Registration Number: NCT00545662
• Lead Sponsor: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

Brief Summary

The Citicoline Brain Injury Treatment (COBRIT) is a randomized, double-blind, placebo controlled, multi-center trial of the effects of 90 days of citicoline on functional outcome in patients with complicated mild, moderate and severe traumatic brain injury.

Detailed Description

Traumatic brain injury (TBI) is a major cause of death and disability. In the United States alone approximately 1.4 million sustain a TBI each year, of which 50,000 people die, and over 200,000 are hospitalized. Despite numerous prior clinical trials no standard pharmacotherapy for the treatment of TBI has been established in either the acute or post acute setting. Citicoline is a naturally occurring endogenous compound. This compound offers the potential of employing neuroprotection, neuro-recovery and neurofacilitation to enhance recovery after TBI.

The primary goal of this study is to assess the efficacy of citicoline compared to placebo on functional and cognitive outcome in participants with traumatic brain injury.

Study Timeline

• Study Start: 2007-07
• Study First Submitted: 2007-10-16
• Study First Submitted QC: 2007-10-16
• Study First Posted: 2007-10-17
• Primary Completion: 2011-05
• Study Completion: 2011-05
• Results First Submitted: 2011-11-29
• Status Verified: 2012-11
• Results First Submitted QC: 2012-11-16
• Last Update Submitted: 2012-11-16
• Results First Posted: 2012-12-19
• Last Update Posted: 2012-12-19

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 1213

Inclusion Criteria

1. Non-penetrating traumatic brain injury.
2. Age 18 (19 in Alabama) - 70 years.
3. GCS criteria on/off paralytics as specified in protocol
4. Reasonable expectation of completion of outcomes measures at a network center at six months post-injury.
5. Able to swallow oral medication or, if unable to swallow, a gastric tube or peg are placed by 23 hours after injury.
6. Reasonable expectation of enrollment within 24-hour time window.
7. English-speaking

Exclusion Criteria

1. Intubated patients with GCS motor score = 6 and not meeting CT criteria.
2. Bilaterally fixed and dilated pupils
3. Positive pregnancy test, known pregnancy, or currently breast feeding
4. Evidence of diseases that interfere with outcome assessment
5. Current acetylcholinesterase inhibitor use (Appendix 1)
6. Imminent death or current life-threatening disease
7. Currently enrolled in another study
8. Prisoners

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo	Placebo tablets formulated to resemble the citicoline treatment.
Citicoline	citicoline	Experimental treatment administered orally or enterally depending upon whether the participant can swallow at 1,000 mg twice a day for 90 days or until the 90-day outcome assessment.

Primary Outcome Measures

Name	Time	Method
Functional and Cognitive Outcome	90 days	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.

Trial Locations

Locations (8)

University of Pittsburgh; 🇺🇸 Pittsburgh, Pennsylvania, United States

Virginia Commonwealth University; 🇺🇸 Richmond, Virginia, United States

University of Maryland, Baltimore; 🇺🇸 Baltimore, Maryland, United States

Temple University; 🇺🇸 Philadelphia, Pennsylvania, United States

University of Texas, Southwestern Medical Center; 🇺🇸 Dallas, Texas, United States

University of Tennessee Health Sciences Center; 🇺🇸 Memphis, Tennessee, United States

University of Washington; 🇺🇸 Seattle, Washington, United States

University of Alabama at Birmingham; 🇺🇸 Birmingham, Alabama, United States