Traumatic Brain InjuryPhase 3COBRITNCT00545662
Study of Citicoline for the Treatment of Traumatic Brain Injury (COBRIT)
A Phase 3 study testing citicoline in people with Traumatic Brain Injury, run by Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) at 8 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Traumatic Brain Injury
- What is being tested?
- citicoline
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 1,213 participants
- Where
- 8 sitesUnited States
- Study dates
- Jul 2007to May 2011
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Non-penetrating traumatic brain injury.
- Age 18 (19 in Alabama) - 70 years.
- GCS criteria on/off paralytics as specified in protocol
- Reasonable expectation of completion of outcomes measures at a network center at six months post-injury.
- Able to swallow oral medication or, if unable to swallow, a gastric tube or peg are placed by 23 hours after injury.
- Reasonable expectation of enrollment within 24-hour time window.
- English-speaking
Who cannot join
- Intubated patients with GCS motor score = 6 and not meeting CT criteria.
- Bilaterally fixed and dilated pupils
- Positive pregnancy test, known pregnancy, or currently breast feeding
- Evidence of diseases that interfere with outcome assessment
- Current acetylcholinesterase inhibitor use (Appendix 1)
- Imminent death or current life-threatening disease
- Currently enrolled in another study
- Prisoners
Trial locations and contacts
8 sites in 1 country.
8 sites in 1 country
United States8 sites
University of Maryland, Baltimore
Baltimore, Maryland, 21201
University of Alabama at Birmingham
Birmingham, Alabama, 35294-3295
University of Texas, Southwestern Medical Center
Dallas, Texas, 75390
University of Tennessee Health Sciences Center
Memphis, Tennessee, 38163
Temple University
Philadelphia, Pennsylvania, 19141-3099
University of Pittsburgh
Pittsburgh, Pennsylvania, 15213-3221
Virginia Commonwealth University
Richmond, Virginia, 23298-0677
University of Washington
Seattle, Washington, 23298-0631
About this study
Official title: Citicoline Brain Injury Treatment Trial
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.
Read the 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.
- Conditions
- Traumatic Brain Injury
- Being tested
- Placebo, citicoline
- Keywords
- traumatic brain injury, cognition, behavioral outcome, functional outcome, treatment, early intervention, citicoline
- Medical subject headings
- Brain Injuries, Traumatic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PlaceboDrug
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.
citicolineDrug
Also called CDP-Choline, Cytidine 5-diphosphocholine, Somazina
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.
| Study group | Role | What they receive |
|---|---|---|
| Placebo | Experimental | Placebo tablets formulated to resemble the citicoline treatment. Receives: Drug: Placebo |
| 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. Receives: Drug: citicoline |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 90 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Oct 2007 (estimated)
- Study startJul 2007
- Primary completionMay 2011
- Study completionMay 2011
Why it stopped: Trial stopped due to futility.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Traumatic Brain InjuryStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 1,213 participants (actual)
Sponsor and investigators
- Lead sponsor
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
- Sponsor type
- US National Institutes of Health
- Responsible party
- Principal investigator, William Friedewald, Columbia University
- Investigators
- Sherry Melton, MD, Principal investigator, University of Alabama at BirminghamHoward Eisenberg, MD, Principal investigator, University of Maryland, BaltimoreJack Jallo, MD, PhD, Principal investigator, Temple UniversityJoseph Ricker, PhD, Principal investigator, University of PittsburghShelly Timmons, MD, PhD, Principal investigator, University of Tennessee Health Sciences CenterRamon Diaz-Arrastia, MD, PhD, Principal investigator, University of Texas Southwestern Medical CenterJohn Ward, MD, Principal investigator, Virginia Commonwealth UniversityNancy Temkin, PhD, Principal investigator, University of Washington
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00545662
- Sponsor's protocol ID
- BA-HD042
- Other IDs
- HD042687-04, HD042738-05, HD042678-03, HD042653-05, HD042689-05, HD042736-04, HD 042686-01A1, HD042652-04
- Acronym
- COBRIT
- Status last verified
- Nov 2012
- First submitted
- 16 Oct 2007
- Last updated
- 19 Dec 2012
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
Baird CL, Mullin HA, Hillary FG. Into the multiverse: Applications to neuropsychology. Neuropsychology. 2026 Sep 21. doi: 10.1037/neu0001094. Online ahead of print.
PubMed 42765966Zafonte 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.
PubMed 23168823
Study at a glance
From the registry record, last updated by the sponsor on 19 Dec 2012. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Citicoline Brain Injury Treatment Trial
- ClinicalTrials.gov ID
- NCT00545662
- Acronym / sponsor ID
- COBRIT / BA-HD042
- Conditions
- Traumatic Brain Injury
- Keywords
- traumatic brain injury, cognition, behavioral outcome, functional outcome, treatment, early intervention, citicoline
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Trial stopped due to futility.
- Enrolment
- 1,213 participants (actual)
- Lead sponsor
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)US National Institutes of Health
- Study start
- Jul 2007
- Primary completion
- May 2011 (actual)
- Study completion
- May 2011 (actual)
- First posted
- 17 Oct 2007 (estimated)
- Results
- Posted 19 Dec 2012
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Placebo | Experimental | Drug: PlaceboPlacebo tablets formulated to resemble the citicoline treatment. |
| Citicoline | Experimental | Drug: citicolineExperimental 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. |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- Non-penetrating traumatic brain injury.
- Age 18 (19 in Alabama) - 70 years.
- GCS criteria on/off paralytics as specified in protocol
- Reasonable expectation of completion of outcomes measures at a network center at six months post-injury.
- Able to swallow oral medication or, if unable to swallow, a gastric tube or peg are placed by 23 hours after injury.
Key exclusion criteria (8 listed)
- Intubated patients with GCS motor score = 6 and not meeting CT criteria.
- Bilaterally fixed and dilated pupils
- Positive pregnancy test, known pregnancy, or currently breast feeding
- Evidence of diseases that interfere with outcome assessment
- Current acetylcholinesterase inhibitor use (Appendix 1)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| PlaceboDrug 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. | Drug | Placebo |
| citicolineAlso: CDP-Choline, Cytidine 5-diphosphocholine, Somazina1000 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. | Drug | Citicoline |
Primary outcome
Functional and Cognitive Outcome
Time frame: 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.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Dec 2012.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 42765966Baird CL, Mullin HA, Hillary FG. Into the multiverse: Applications to neuropsychology. Neuropsychology. 2026 Sep 21. doi: 10.1037/neu0001094. Online ahead of print.
- Derived from this study: PubMed 23168823Zafonte 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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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Sherry Melton, MD principal investigator
University of Alabama at Birmingham
Howard Eisenberg, MD principal investigator
University of Maryland, Baltimore
Jack Jallo, MD, PhD principal investigator
Temple University
8 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing citicoline in people with Traumatic Brain Injury, run by Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) at 8 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 19 Dec 2012. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 8 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 19 Dec 2012). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Functional and Cognitive Outcome (time frame: 90 days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00545662, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Dec 2012.