Trial Outcomes & Findings for Effectiveness of Amantadine Hydrochloride for Treatment of Severe Traumatic Brain Injury (TBI) (NCT NCT00970944)
NCT ID: NCT00970944
Last Updated: 2012-09-24
Results Overview
Measure of function after traumatic brain injury (TBI) intended to measure function from "coma to community." Minimum score= 0; Maximum score= 29 (High scores are indicative of greater degree of disability).
Recruitment status
COMPLETED
Study phase
PHASE2/PHASE3
Target enrollment
184 participants
Primary outcome timeframe
Randomization and weekly for 6 weeks. The primary study endpoint was week 4 and drug washout was week 6.
Results posted on
2012-09-24
Participant Flow
February 23,2003 through March 15, 2010. Eleven rehabilitations centers in the USA (8) and Europe (3)
Participant milestones
| Measure |
Amantadine HCL
100mg BID administered for 2 weeks, then increased to 150mg BID in week 3 if change on primary outcome measure (ie Disability Rating Scale, DRS) was less than 2 points after week 2. If change in DRS score remained less than 2 points after week 3, dose was increased to 200mg BID in week 4.
|
Placebo
Visually identical compound administered in the same manner (ie enterally) as the actual study drug.
|
|---|---|---|
|
Overall Study
STARTED
|
87
|
97
|
|
Overall Study
COMPLETED
|
86
|
95
|
|
Overall Study
NOT COMPLETED
|
1
|
2
|
Reasons for withdrawal
| Measure |
Amantadine HCL
100mg BID administered for 2 weeks, then increased to 150mg BID in week 3 if change on primary outcome measure (ie Disability Rating Scale, DRS) was less than 2 points after week 2. If change in DRS score remained less than 2 points after week 3, dose was increased to 200mg BID in week 4.
|
Placebo
Visually identical compound administered in the same manner (ie enterally) as the actual study drug.
|
|---|---|---|
|
Overall Study
Death
|
1
|
0
|
|
Overall Study
Physician Decision
|
0
|
2
|
Baseline Characteristics
Effectiveness of Amantadine Hydrochloride for Treatment of Severe Traumatic Brain Injury (TBI)
Baseline characteristics by cohort
| Measure |
Amantadine HCL
n=87 Participants
100mg BID administered for 2 weeks, then increased to 150mg BID in week 3 if change on primary outcome measure (ie Disability Rating Scale, DRS) was less than 2 points after week 2. If change in DRS score remained less than 2 points after week 3, dose was increased to 200mg BID in week 4.
|
Placebo
n=97 Participants
Visually identical compound administered in the same manner (ie enterally) as the actual study drug.
|
Total
n=184 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Categorical
<=18 years
|
5 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
6 Participants
n=5 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
82 Participants
n=5 Participants
|
96 Participants
n=7 Participants
|
178 Participants
n=5 Participants
|
|
Age, Categorical
>=65 years
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Age Continuous
|
35.5 years
STANDARD_DEVIATION 15.3 • n=5 Participants
|
37.2 years
STANDARD_DEVIATION 15.4 • n=7 Participants
|
36.4 years
STANDARD_DEVIATION 15.4 • n=5 Participants
|
|
Sex: Female, Male
Female
|
23 Participants
n=5 Participants
|
28 Participants
n=7 Participants
|
51 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
64 Participants
n=5 Participants
|
69 Participants
n=7 Participants
|
133 Participants
n=5 Participants
|
|
Region of Enrollment
United States
|
61 participants
n=5 Participants
|
73 participants
n=7 Participants
|
134 participants
n=5 Participants
|
|
Region of Enrollment
Denmark
|
3 participants
n=5 Participants
|
2 participants
n=7 Participants
|
5 participants
n=5 Participants
|
|
Region of Enrollment
Germany
|
23 participants
n=5 Participants
|
22 participants
n=7 Participants
|
45 participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Randomization and weekly for 6 weeks. The primary study endpoint was week 4 and drug washout was week 6.Population: Analyses were conducted according to the intention-to-treat principle. 184 subjects were randomized and included for analysis. Since missing data were infrequent and unrelated to the study outcome, imputation methods were not undertaken.
Measure of function after traumatic brain injury (TBI) intended to measure function from "coma to community." Minimum score= 0; Maximum score= 29 (High scores are indicative of greater degree of disability).
Outcome measures
| Measure |
Amantadine
n=87 Participants
Amantadine (200-400 mg/day)
|
Placebo
n=97 Participants
Visually identical compound administered in the same manner (ie enterally) as the study drug.
|
|---|---|---|
|
Disability Rating Scale: Functional Status
Week 4 (Primary endpoint)
|
17.3 units on a scale
Standard Deviation 4.7
|
18.7 units on a scale
Standard Deviation 4.5
|
|
Disability Rating Scale: Functional Status
Week 6 (Drug washout)
|
17.1 units on a scale
Standard Deviation 5.2
|
17.8 units on a scale
Standard Deviation 5.3
|
SECONDARY outcome
Timeframe: Week 4 (primary endpoint); Week 6 (post-washout)Population: Analyses were conducted according to the ITT principle so that all 184 patients randomized were included for analysis. Imputation techniques were not undertaken since missing data were infrequent and unrelated to study outcome.
Measure of neurobehavioral function and clinical change for individuals with severe alterations of consciousness. Minimum score= 0; Maximum score= 23 (Higher scores are indicative of a higher-level of neurobehavioral function).
Outcome measures
| Measure |
Amantadine
n=87 Participants
Amantadine (200-400 mg/day)
|
Placebo
n=97 Participants
Visually identical compound administered in the same manner (ie enterally) as the study drug.
|
|---|---|---|
|
JFK Coma Recovery Scale-Revised: Neurobehavioral Status
Week 4 (Primary endpoint)
|
15.8 units on a scale
Standard Deviation 6.1
|
14.2 units on a scale
Standard Deviation 6.6
|
|
JFK Coma Recovery Scale-Revised: Neurobehavioral Status
Week 6 (Post-washout)
|
15.7 units on a scale
Standard Deviation 6.3
|
15.1 units on a scale
Standard Deviation 6.8
|
Adverse Events
Amantadine HCL
Serious events: 15 serious events
Other events: 54 other events
Deaths: 0 deaths
Placebo
Serious events: 19 serious events
Other events: 51 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Amantadine HCL
n=87 participants at risk
100mg BID administered for 2 weeks, then increased to 150mg BID in week 3 if change on primary outcome measure (ie Disability Rating Scale, DRS) was less than 2 points after week 2. If change in DRS score remained less than 2 points after week 3, dose was increased to 200mg BID in week 4.
|
Placebo
n=97 participants at risk
Visually identical compound administered in the same manner (ie enterally) as the actual study drug.
|
|---|---|---|
|
Nervous system disorders
Epilepsy
|
0.00%
0/87
|
2.1%
2/97 • Number of events 2
|
|
Nervous system disorders
Hydrocephalus
|
3.4%
3/87 • Number of events 3
|
2.1%
2/97 • Number of events 2
|
|
Nervous system disorders
Intracranial Hemorrage
|
0.00%
0/87
|
1.0%
1/97 • Number of events 1
|
|
Nervous system disorders
Other Neurologic
|
1.1%
1/87 • Number of events 1
|
1.0%
1/97 • Number of events 1
|
|
Psychiatric disorders
Hypoarousal/Lethargy/Somnolence
|
0.00%
0/87
|
1.0%
1/97 • Number of events 1
|
|
Nervous system disorders
Autonomic Storm
|
0.00%
0/87
|
1.0%
1/97 • Number of events 1
|
|
Gastrointestinal disorders
Other Gastrointestinal Problems
|
2.3%
2/87 • Number of events 2
|
3.1%
3/97 • Number of events 3
|
|
Respiratory, thoracic and mediastinal disorders
Pneumonia
|
6.9%
6/87 • Number of events 6
|
2.1%
2/97 • Number of events 2
|
|
Infections and infestations
Infection
|
3.4%
3/87 • Number of events 3
|
5.2%
5/97 • Number of events 5
|
|
General disorders
General Medical Problems
|
1.1%
1/87 • Number of events 1
|
2.1%
2/97 • Number of events 2
|
|
Blood and lymphatic system disorders
Leukocytosis
|
0.00%
0/87
|
1.0%
1/97 • Number of events 1
|
|
General disorders
Vomiting
|
0.00%
0/87
|
1.0%
1/97 • Number of events 1
|
|
Cardiac disorders
Cardiac arrest
|
1.1%
1/87 • Number of events 1
|
0.00%
0/97
|
|
Renal and urinary disorders
Urinary tract infection
|
1.1%
1/87 • Number of events 1
|
0.00%
0/97
|
|
Blood and lymphatic system disorders
Other Abnormal Laboratory
|
0.00%
0/87
|
1.0%
1/97 • Number of events 1
|
Other adverse events
| Measure |
Amantadine HCL
n=87 participants at risk
100mg BID administered for 2 weeks, then increased to 150mg BID in week 3 if change on primary outcome measure (ie Disability Rating Scale, DRS) was less than 2 points after week 2. If change in DRS score remained less than 2 points after week 3, dose was increased to 200mg BID in week 4.
|
Placebo
n=97 participants at risk
Visually identical compound administered in the same manner (ie enterally) as the actual study drug.
|
|---|---|---|
|
Musculoskeletal and connective tissue disorders
Hypertonia / Spasticity
|
20.7%
18/87 • Number of events 21
|
14.4%
14/97 • Number of events 18
|
|
General disorders
Insomnia / Sleep Disturbance
|
13.8%
12/87 • Number of events 14
|
14.4%
14/97 • Number of events 15
|
|
Psychiatric disorders
Agitation / Aggression
|
13.8%
12/87 • Number of events 16
|
11.3%
11/97 • Number of events 14
|
|
Infections and infestations
Infections
|
11.5%
10/87 • Number of events 14
|
15.5%
15/97 • Number of events 16
|
|
Renal and urinary disorders
Urinary tract infection
|
14.9%
13/87 • Number of events 15
|
12.4%
12/97 • Number of events 13
|
|
General disorders
General Medical Problems
|
10.3%
9/87 • Number of events 10
|
11.3%
11/97 • Number of events 16
|
Additional Information
Joseph T Giacino, PhD
Spaulding Rehabilitation Hospital
Phone: 617-573-2757
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place
Restriction type: LTE60