Trial Outcomes & Findings for Study of Citicoline for the Treatment of Traumatic Brain Injury (COBRIT) (NCT NCT00545662)
NCT ID: NCT00545662
Last Updated: 2012-12-19
Results Overview
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.
TERMINATED
PHASE3
1213 participants
90 days
2012-12-19
Participant Flow
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.
Participant milestones
| Measure |
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.
|
|---|---|---|
|
Overall Study
STARTED
|
606
|
607
|
|
Overall Study
COMPLETED
|
521
|
528
|
|
Overall Study
NOT COMPLETED
|
85
|
79
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Study of Citicoline for the Treatment of Traumatic Brain Injury (COBRIT)
Baseline characteristics by cohort
| Measure |
Control
n=606 Participants
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
n=607 Participants
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
n=1213 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
568 Participants
n=5 Participants
|
563 Participants
n=7 Participants
|
1131 Participants
n=5 Participants
|
|
Age, Categorical
>=65 years
|
38 Participants
n=5 Participants
|
43 Participants
n=7 Participants
|
81 Participants
n=5 Participants
|
|
Age Continuous
|
41.1 years
STANDARD_DEVIATION 15.5 • n=5 Participants
|
39.7 years
STANDARD_DEVIATION 16.2 • n=7 Participants
|
40.4 years
STANDARD_DEVIATION 15.9 • n=5 Participants
|
|
Sex: Female, Male
Female
|
159 Participants
n=5 Participants
|
151 Participants
n=7 Participants
|
310 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
447 Participants
n=5 Participants
|
456 Participants
n=7 Participants
|
903 Participants
n=5 Participants
|
|
Region of Enrollment
United States
|
606 participants
n=5 Participants
|
607 participants
n=7 Participants
|
1213 participants
n=5 Participants
|
PRIMARY outcome
Timeframe: 90 daysPopulation: 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.
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.
Outcome measures
| Measure |
Control
n=509 Participants
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
n=508 Participants
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.
|
|---|---|---|
|
Functional and Cognitive Outcome
Processing Speed Index
|
53.28 percentage of participants
|
52.68 percentage of participants
|
|
Functional and Cognitive Outcome
Trail Making A
|
61.96 percentage of participants
|
64.96 percentage of participants
|
|
Functional and Cognitive Outcome
Glasgow Outcome Scale - Extended
|
35.56 percentage of participants
|
35.43 percentage of participants
|
|
Functional and Cognitive Outcome
California Verbal Learning Test
|
60.48 percentage of participants
|
57.71 percentage of participants
|
|
Functional and Cognitive Outcome
Trail Making B
|
71.05 percentage of participants
|
74.44 percentage of participants
|
|
Functional and Cognitive Outcome
Digit Span
|
84.02 percentage of participants
|
86.50 percentage of participants
|
|
Functional and Cognitive Outcome
Stroop Task 1
|
67.95 percentage of participants
|
65.31 percentage of participants
|
|
Functional and Cognitive Outcome
Stroop Task 2
|
66.59 percentage of participants
|
68.29 percentage of participants
|
|
Functional and Cognitive Outcome
Controlled Oral Word Association Test
|
42.68 percentage of participants
|
37.32 percentage of participants
|
Adverse Events
Control
Treatment
Serious adverse events
| Measure |
Control
n=606 participants at risk
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
n=607 participants at risk
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.
|
|---|---|---|
|
Nervous system disorders
CNS
|
10.2%
62/606
|
10.4%
63/607
|
|
Vascular disorders
Cardiovascular
|
2.3%
14/606
|
2.3%
14/607
|
|
Respiratory, thoracic and mediastinal disorders
Respiratory
|
5.1%
31/606
|
4.0%
24/607
|
|
Skin and subcutaneous tissue disorders
Dermatology/Skin
|
0.50%
3/606
|
0.16%
1/607
|
|
Endocrine disorders
Endocrine
|
0.17%
1/606
|
0.49%
3/607
|
|
Gastrointestinal disorders
Digestive
|
1.2%
7/606
|
2.1%
13/607
|
|
Blood and lymphatic system disorders
Circulatory
|
0.99%
6/606
|
1.8%
11/607
|
|
Immune system disorders
Immune
|
0.83%
5/606
|
0.66%
4/607
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal
|
0.83%
5/606
|
0.82%
5/607
|
|
Renal and urinary disorders
Excretory/Urinary
|
0.83%
5/606
|
0.49%
3/607
|
Other adverse events
| Measure |
Control
n=606 participants at risk
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
n=607 participants at risk
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.
|
|---|---|---|
|
Gastrointestinal disorders
Gastrointestinal
|
30.4%
184/606
|
31.8%
193/607
|
|
Investigations
Abnormal Lab
|
23.6%
143/606
|
28.8%
175/607
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal
|
25.9%
157/606
|
21.7%
132/607
|
|
Nervous system disorders
Neurological
|
52.6%
319/606
|
50.7%
308/607
|
|
Infections and infestations
Fever/Infection
|
19.5%
118/606
|
20.9%
127/607
|
|
Vascular disorders
Cardiovascular
|
14.5%
88/606
|
14.2%
86/607
|
|
Renal and urinary disorders
Genitourinary
|
12.0%
73/606
|
12.4%
75/607
|
|
Eye disorders
Ophthalmologic
|
8.4%
51/606
|
7.9%
48/607
|
|
Respiratory, thoracic and mediastinal disorders
Respiratory
|
21.8%
132/606
|
23.6%
143/607
|
|
Skin and subcutaneous tissue disorders
Dermatologic/Skin
|
11.4%
69/606
|
9.7%
59/607
|
|
General disorders
Diaphoresis
|
5.9%
36/606
|
4.6%
28/607
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place