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| ID | Type | Description | Link |
|---|---|---|---|
| HD042687-04 | |||
| HD042738-05 | |||
| HD042678-03 | |||
| HD042653-05 | |||
| HD042689-05 | |||
| HD042736-04 | |||
| HD 042686-01A1 | |||
| HD042652-04 | |||
| HD042823-05 |
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Trial stopped due to futility.
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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Placebo | Experimental | Placebo tablets formulated to resemble the citicoline treatment. |
|
| Citicoline | Experimental | 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. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Placebo | Drug | Drug Placebo Inactive twice a day given orally or enterally. The first dose is given within 24 hours of injury and treatment continues until 90 days or until the 90-day outcome assessment. |
| Measure | Description | Time Frame |
|---|---|---|
| Functional and Cognitive Outcome | 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. | 90 days |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Sherry Melton, MD | University of Alabama at Birmingham | Principal Investigator |
| Howard Eisenberg, MD | University of Maryland, Baltimore | Principal Investigator |
| Jack Jallo, MD, PhD | Temple University | Principal Investigator |
| Joseph Ricker, PhD | University of Pittsburgh | Principal Investigator |
| Shelly Timmons, MD, PhD | University of Tennessee Health Sciences Center | Principal Investigator |
| Ramon Diaz-Arrastia, MD, PhD | University of Texas Southwestern Medical Center | Principal Investigator |
| John Ward, MD | Virginia Commonwealth University | Principal Investigator |
| Nancy Temkin, PhD | University of Washington | Principal Investigator |
| Beth Ansel, PhD | National Institute of Child Health and Human Development, National Center for Medical Rehabilitation Research |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of Alabama at Birmingham | Birmingham | Alabama | 35294-3295 | United States | ||
| University of Maryland, Baltimore |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 23168823 | Derived | Zafonte RD, Bagiella E, Ansel BM, Novack TA, Friedewald WT, Hesdorffer DC, Timmons SD, Jallo J, Eisenberg H, Hart T, Ricker JH, Diaz-Arrastia R, Merchant RE, Temkin NR, Melton S, Dikmen SS. Effect of citicoline on functional and cognitive status among patients with traumatic brain injury: Citicoline Brain Injury Treatment Trial (COBRIT). JAMA. 2012 Nov 21;308(19):1993-2000. doi: 10.1001/jama.2012.13256. |
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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.
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| ID | Title | Description |
|---|---|---|
| FG000 | 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. |
| FG001 | Treatment |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| citicoline | Drug | 1000 mg twice a day orally or enterally. The first dose is within 24 hours of injury and treatment continues for 90-days or until the 90-day outcome assessment. |
|
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| William Friedewald, MD | Columbia University Department of Biostatistics | Principal Investigator |
| Baltimore |
| Maryland |
| 21201 |
| United States |
| Temple University | Philadelphia | Pennsylvania | 19141-3099 | United States |
| University of Pittsburgh | Pittsburgh | Pennsylvania | 15213-3221 | United States |
| University of Tennessee Health Sciences Center | Memphis | Tennessee | 38163 | United States |
| University of Texas, Southwestern Medical Center | Dallas | Texas | 75390 | United States |
| Virginia Commonwealth University | Richmond | Virginia | 23298-0677 | United States |
| University of Washington | Seattle | Washington | 23298-0631 | United States |
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. |
| COMPLETED |
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| NOT COMPLETED |
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| ID | Title | Description |
|---|---|---|
| BG000 | 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. |
| BG001 | 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. |
| BG002 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants | Participants |
| ||||||||||||||||||
| Age Continuous | Mean | Standard Deviation | years |
| |||||||||||||||||
| Sex: Female, Male | Count of Participants | Participants |
| ||||||||||||||||||
| Region of Enrollment | Number | participants |
|
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Functional and Cognitive Outcome | 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. | 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. | Posted | Number | percentage of participants | 90 days |
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | 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. | 117 | 606 | 452 | 606 | ||
| EG001 | 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. | 117 | 607 | 449 | 607 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| CNS | Nervous system disorders | Systematic Assessment |
| ||
| Cardiovascular | Vascular disorders | Systematic Assessment |
| ||
| Respiratory | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
| ||
| Dermatology/Skin | Skin and subcutaneous tissue disorders | Systematic Assessment |
| ||
| Endocrine | Endocrine disorders | Systematic Assessment |
| ||
| Digestive | Gastrointestinal disorders | Systematic Assessment |
| ||
| Circulatory | Blood and lymphatic system disorders | Systematic Assessment |
| ||
| Immune | Immune system disorders | Systematic Assessment |
| ||
| Musculoskeletal | Musculoskeletal and connective tissue disorders | Systematic Assessment |
| ||
| Excretory/Urinary | Renal and urinary disorders | Systematic Assessment |
|
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Gastrointestinal | Gastrointestinal disorders | Systematic Assessment |
| ||
| Abnormal Lab | Investigations | Systematic Assessment |
| ||
| Musculoskeletal | Musculoskeletal and connective tissue disorders | Systematic Assessment |
| ||
| Neurological | Nervous system disorders | Systematic Assessment |
| ||
| Fever/Infection | Infections and infestations | Systematic Assessment |
| ||
| Cardiovascular | Vascular disorders | Systematic Assessment |
| ||
| Genitourinary | Renal and urinary disorders | Systematic Assessment |
| ||
| Ophthalmologic | Eye disorders | Systematic Assessment |
| ||
| Respiratory | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
| ||
| Dermatologic/Skin | Skin and subcutaneous tissue disorders | Systematic Assessment |
| ||
| Diaphoresis | General disorders | Systematic Assessment |
|
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr. William Friedewald | Columbia University | 212-305-3017 | wtf1@columbia.edu |
| ID | Term |
|---|---|
| D000070642 | Brain Injuries, Traumatic |
| ID | Term |
|---|---|
| D001930 | Brain Injuries |
| D001927 | Brain Diseases |
| D002493 | Central Nervous System Diseases |
| D009422 | Nervous System Diseases |
| D006259 | Craniocerebral Trauma |
| D020196 | Trauma, Nervous System |
| D014947 | Wounds and Injuries |
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| ID | Term |
|---|---|
| D003566 | Cytidine Diphosphate Choline |
| ID | Term |
|---|---|
| D002794 | Choline |
| D050337 | Trimethyl Ammonium Compounds |
| D000644 | Quaternary Ammonium Compounds |
| D000588 | Amines |
| D009930 | Organic Chemicals |
| D009861 | Onium Compounds |
| D003565 | Cytidine Diphosphate |
| D003597 | Cytosine Nucleotides |
| D011742 | Pyrimidine Nucleotides |
| D011743 | Pyrimidines |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
| D009711 | Nucleotides |
| D009706 | Nucleic Acids, Nucleotides, and Nucleosides |
| D012265 | Ribonucleotides |
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| >=65 years |
|
| Male |
|
| Processing Speed Index |
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| Trail Making A |
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| Trail Making B |
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| Digit Span |
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| Stroop Task 1 |
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| Stroop Task 2 |
|
| Controlled Oral Word Association Test |
|
The odds in the citicoline group were compared to the odds in the placebo group. |
| No |
| Superiority or Other |