Trial Outcomes & Findings for A Safety and Feasibility Study of Enteral LVT vs. Standard of Care for Seizure Control in Pediatric CM (NCT NCT01982812)
NCT ID: NCT01982812
Last Updated: 2016-07-29
Results Overview
Comparing LVT to standard AED the number of minutes spent in seizure per cEEG in the 72 hours after treatment allocation.
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
44 participants
Primary outcome timeframe
72 hours
Results posted on
2016-07-29
Participant Flow
Randomized consecutive, eligible consented children with cerebral malaria during two recruitment periods--January to June 2014 and 2015,
Participant milestones
| Measure |
Oral Levetiracetam
Oral Levetiracetam administered by NG tube.
Oral Levetiracetam: liquid, 40 mg/kg loading dose and 30mg/kg every 12 hours via nasogastric tube for 3 days
|
Comparison Group
2014: Children randomized to routine care who then recieved 20mg/kg phenobarbital with additional doses at the managing clinicians discretion
2015: Children randomized to routine care will phenobarbital given at the discretion of the managing clinician but with a max od 20mg/kg load
|
|---|---|---|
|
Overall Study
STARTED
|
23
|
21
|
|
Overall Study
COMPLETED
|
22
|
11
|
|
Overall Study
NOT COMPLETED
|
1
|
10
|
Reasons for withdrawal
| Measure |
Oral Levetiracetam
Oral Levetiracetam administered by NG tube.
Oral Levetiracetam: liquid, 40 mg/kg loading dose and 30mg/kg every 12 hours via nasogastric tube for 3 days
|
Comparison Group
2014: Children randomized to routine care who then recieved 20mg/kg phenobarbital with additional doses at the managing clinicians discretion
2015: Children randomized to routine care will phenobarbital given at the discretion of the managing clinician but with a max od 20mg/kg load
|
|---|---|---|
|
Overall Study
Death
|
1
|
5
|
|
Overall Study
Adverse Event
|
0
|
5
|
Baseline Characteristics
A Safety and Feasibility Study of Enteral LVT vs. Standard of Care for Seizure Control in Pediatric CM
Baseline characteristics by cohort
| Measure |
Oral Levetiracetam
n=23 Participants
Oral Levetiracetam administered by NG tube.
Oral Levetiracetam: liquid, 40 mg/kg loading dose and 30mg/kg every 12 hours via nasogastric tube for 3 days
|
Standard AED
n=21 Participants
Standard AED regimen
Standard AED: Active comparitor, Standard AED
|
Total
n=44 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Categorical
<=18 years
|
23 Participants
n=5 Participants
|
21 Participants
n=7 Participants
|
44 Participants
n=5 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 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
|
41.4 months
STANDARD_DEVIATION 10.6 • n=5 Participants
|
41.8 months
STANDARD_DEVIATION 16.7 • n=7 Participants
|
41.6 months
STANDARD_DEVIATION 13.7 • n=5 Participants
|
|
Sex: Female, Male
Female
|
10 Participants
n=5 Participants
|
14 Participants
n=7 Participants
|
24 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
13 Participants
n=5 Participants
|
7 Participants
n=7 Participants
|
20 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
African
|
23 participants
n=5 Participants
|
21 participants
n=7 Participants
|
44 participants
n=5 Participants
|
|
cerebral malaria retinopathy (present)
retinopathy positive
|
16 participants
n=5 Participants
|
12 participants
n=7 Participants
|
28 participants
n=5 Participants
|
|
cerebral malaria retinopathy (present)
retinopathy negative
|
7 participants
n=5 Participants
|
9 participants
n=7 Participants
|
16 participants
n=5 Participants
|
PRIMARY outcome
Timeframe: 72 hoursComparing LVT to standard AED the number of minutes spent in seizure per cEEG in the 72 hours after treatment allocation.
Outcome measures
| Measure |
Oral Levetiracetam
n=23 Participants
Oral Levetiracetam administered by NG tube.
Oral Levetiracetam: liquid, 40 mg/kg loading dose and 30mg/kg every 12 hours via nasogastric tube for 3 days
|
Comparison Group
n=21 Participants
2014: Children randomized to routine care who then recieved 20mg/kg phenobarbital with additional doses at the managing clinicians discretion
2015: Children randomized to routine care will phenobarbital given at the discretion of the managing clinician but with a max od 20mg/kg load
|
|---|---|---|
|
Minutes With Seizure on EEG
|
165.2 minutes with seizure
Standard Deviation 265.9
|
464.8 minutes with seizure
Standard Deviation 639.3
|
SECONDARY outcome
Timeframe: 7 daysAdditional AEDs required (including for breakthrough seizures in LVT group) during admission for seizure control (yes/no)
Outcome measures
| Measure |
Oral Levetiracetam
n=23 Participants
Oral Levetiracetam administered by NG tube.
Oral Levetiracetam: liquid, 40 mg/kg loading dose and 30mg/kg every 12 hours via nasogastric tube for 3 days
|
Comparison Group
n=21 Participants
2014: Children randomized to routine care who then recieved 20mg/kg phenobarbital with additional doses at the managing clinicians discretion
2015: Children randomized to routine care will phenobarbital given at the discretion of the managing clinician but with a max od 20mg/kg load
|
|---|---|---|
|
Required Additional AED
|
18 Participants requiring additional AEDs
|
18 Participants requiring additional AEDs
|
SECONDARY outcome
Timeframe: 7 daysPopulation: Comparing mean time to coma resolution in hours among survivors
The mean time in hours from admission until the subject reaches Blantyre Coma Scale of greater than or equal to 4. Participants who died are excluded from this analysis. The Blantyre Coma Score has ranges from 0-5 based upon the a sum of the following 3 domains- Eye movement 1 - Watches or follows 0 - Fails to watch or follow Best motor response 2 - Localizes painful stimulus 1 - Withdraws limb from painful stimulus 0 - No response or inappropriate response Best verbal response 2 - Cries appropriately with pain, or, if verbal, speaks 1 - Moan or abnormal cry with pain 0 - No vocal response to pain
Outcome measures
| Measure |
Oral Levetiracetam
n=22 Participants
Oral Levetiracetam administered by NG tube.
Oral Levetiracetam: liquid, 40 mg/kg loading dose and 30mg/kg every 12 hours via nasogastric tube for 3 days
|
Comparison Group
n=16 Participants
2014: Children randomized to routine care who then recieved 20mg/kg phenobarbital with additional doses at the managing clinicians discretion
2015: Children randomized to routine care will phenobarbital given at the discretion of the managing clinician but with a max od 20mg/kg load
|
|---|---|---|
|
Mean Time From Admission to BCS >/= 4
|
35.4 hours of coma from admission
Standard Deviation 29.0
|
34.6 hours of coma from admission
Standard Deviation 27.8
|
SECONDARY outcome
Timeframe: 7 daysNeurologic outcome in 3 categories-- 1. Neurologically intact at discharge 2. Neurologic sequelae at discharge--specifically new sensory or motor deficits, ongoing seizures, or behavioral abnormalities based upon a physician examination at discharge 3. Died during admission, never discharged
Outcome measures
| Measure |
Oral Levetiracetam
n=23 Participants
Oral Levetiracetam administered by NG tube.
Oral Levetiracetam: liquid, 40 mg/kg loading dose and 30mg/kg every 12 hours via nasogastric tube for 3 days
|
Comparison Group
n=21 Participants
2014: Children randomized to routine care who then recieved 20mg/kg phenobarbital with additional doses at the managing clinicians discretion
2015: Children randomized to routine care will phenobarbital given at the discretion of the managing clinician but with a max od 20mg/kg load
|
|---|---|---|
|
Sequelae
Neurologically intact at discharge
|
19 participants
|
14 participants
|
|
Sequelae
Neurologic sequelae at discharge
|
3 participants
|
2 participants
|
|
Sequelae
Died during admission
|
1 participants
|
5 participants
|
Adverse Events
Oral Levetiracetam
Serious events: 5 serious events
Other events: 15 other events
Deaths: 0 deaths
Comparison Group
Serious events: 8 serious events
Other events: 18 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Oral Levetiracetam
n=23 participants at risk
Oral Levetiracetam administered by NG tube.
Oral Levetiracetam: liquid, 40 mg/kg loading dose and 30mg/kg every 12 hours via nasogastric tube for 3 days
|
Comparison Group
n=21 participants at risk
2014: Children randomized to routine care who then recieved 20mg/kg phenobarbital with additional doses at the managing clinicians discretion
2015: Children randomized to routine care will phenobarbital given at the discretion of the managing clinician but with a max od 20mg/kg load
|
|---|---|---|
|
Nervous system disorders
death
|
4.3%
1/23 • Number of events 1 • 1 month post enrollment
|
23.8%
5/21 • Number of events 5 • 1 month post enrollment
|
|
Hepatobiliary disorders
elevated AST
|
13.0%
3/23 • Number of events 4 • 1 month post enrollment
|
9.5%
2/21 • Number of events 2 • 1 month post enrollment
|
|
Blood and lymphatic system disorders
thrombocytopenia
|
8.7%
2/23 • Number of events 2 • 1 month post enrollment
|
4.8%
1/21 • Number of events 1 • 1 month post enrollment
|
|
Metabolism and nutrition disorders
hyperkalemia
|
0.00%
0/23 • 1 month post enrollment
|
0.00%
0/21 • 1 month post enrollment
|
|
Renal and urinary disorders
Acute kidney injury
|
4.3%
1/23 • Number of events 1 • 1 month post enrollment
|
0.00%
0/21 • 1 month post enrollment
|
|
Respiratory, thoracic and mediastinal disorders
respiratory suppression or aspiration
|
0.00%
0/23 • 1 month post enrollment
|
14.3%
3/21 • Number of events 3 • 1 month post enrollment
|
|
Blood and lymphatic system disorders
Anemia (persistent)
|
0.00%
0/23 • 1 month post enrollment
|
0.00%
0/21 • 1 month post enrollment
|
|
Hepatobiliary disorders
elevated ALT
|
0.00%
0/23 • 1 month post enrollment
|
0.00%
0/21 • 1 month post enrollment
|
|
Hepatobiliary disorders
elevated alkaline phosphatase
|
0.00%
0/23 • 1 month post enrollment
|
0.00%
0/21 • 1 month post enrollment
|
Other adverse events
| Measure |
Oral Levetiracetam
n=23 participants at risk
Oral Levetiracetam administered by NG tube.
Oral Levetiracetam: liquid, 40 mg/kg loading dose and 30mg/kg every 12 hours via nasogastric tube for 3 days
|
Comparison Group
n=21 participants at risk
2014: Children randomized to routine care who then recieved 20mg/kg phenobarbital with additional doses at the managing clinicians discretion
2015: Children randomized to routine care will phenobarbital given at the discretion of the managing clinician but with a max od 20mg/kg load
|
|---|---|---|
|
Nervous system disorders
myoclonus
|
4.3%
1/23 • Number of events 1 • 1 month post enrollment
|
0.00%
0/21 • 1 month post enrollment
|
|
Blood and lymphatic system disorders
Anemia with persistent low retics
|
0.00%
0/23 • 1 month post enrollment
|
4.8%
1/21 • Number of events 1 • 1 month post enrollment
|
|
Hepatobiliary disorders
Increased AST
|
21.7%
5/23 • Number of events 7 • 1 month post enrollment
|
33.3%
7/21 • Number of events 10 • 1 month post enrollment
|
|
Blood and lymphatic system disorders
Thrombocytopenia
|
8.7%
2/23 • Number of events 2 • 1 month post enrollment
|
4.8%
1/21 • Number of events 1 • 1 month post enrollment
|
|
Blood and lymphatic system disorders
elevated platelet count
|
4.3%
1/23 • Number of events 1 • 1 month post enrollment
|
9.5%
2/21 • Number of events 2 • 1 month post enrollment
|
|
Blood and lymphatic system disorders
Decreased reticulocyte count
|
4.3%
1/23 • Number of events 1 • 1 month post enrollment
|
19.0%
4/21 • Number of events 4 • 1 month post enrollment
|
|
Cardiac disorders
Abnormal ECG
|
0.00%
0/23 • 1 month post enrollment
|
4.8%
1/21 • Number of events 1 • 1 month post enrollment
|
|
Nervous system disorders
Excess sedation
|
0.00%
0/23 • 1 month post enrollment
|
4.8%
1/21 • Number of events 1 • 1 month post enrollment
|
|
Hepatobiliary disorders
Increased ALT
|
17.4%
4/23 • Number of events 4 • 1 month post enrollment
|
19.0%
4/21 • Number of events 7 • 1 month post enrollment
|
|
Hepatobiliary disorders
Increased alkaline phosphotase
|
13.0%
3/23 • Number of events 3 • 1 month post enrollment
|
23.8%
5/21 • Number of events 7 • 1 month post enrollment
|
|
Metabolism and nutrition disorders
Increased potassium
|
30.4%
7/23 • Number of events 7 • 1 month post enrollment
|
19.0%
4/21 • Number of events 4 • 1 month post enrollment
|
|
Metabolism and nutrition disorders
Increased chloride
|
8.7%
2/23 • Number of events 2 • 1 month post enrollment
|
0.00%
0/21 • 1 month post enrollment
|
|
Gastrointestinal disorders
Vomiting
|
4.3%
1/23 • Number of events 1 • 1 month post enrollment
|
0.00%
0/21 • 1 month post enrollment
|
|
Metabolism and nutrition disorders
increased phosphate
|
26.1%
6/23 • Number of events 6 • 1 month post enrollment
|
4.8%
1/21 • Number of events 1 • 1 month post enrollment
|
|
Metabolism and nutrition disorders
increased calcium
|
4.3%
1/23 • Number of events 1 • 1 month post enrollment
|
0.00%
0/21 • 1 month post enrollment
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place