Trial Outcomes & Findings for Cognitive AED Outcomes in Pediatric Localization Related Epilepsy (COPE) (NCT NCT01891890)

NCT ID: NCT01891890

Last Updated: 2017-09-19

Results Overview

The Conners' Continuous Performance Test II (CPT-II) is a measure of sustained attention. Letters are individually presented on a computer screen, and participants are instructed to press the space bar when they are presented with any letter except the letter "X". For children younger than 6 years of age at enrollment, the Kiddie CPT will be used in which the child is instructed to press the space bar every time the ball appears on the screen. The outcome measure is a confidence index representing the probability that the respondent has a clinically relevant problem in sustained attention. Possible scores range from 0 to 100. Scores between 40 and 60 are considered inconclusive while scores above 60 indicate that the child exhibits inattentiveness.

• Recruitment status: TERMINATED
• Study phase: PHASE3
• Target enrollment: 72 participants
• Primary outcome timeframe: Baseline, Month 6
• Results posted on: 2017-09-19

Participant Flow

Participants were recruited from 14 pediatric practices in the United States of America between August 2013 and October 2015.

In total, 78 individuals consented to participate in the trial. Of these 6 were found to be ineligible or declined to participate prior to receiving the intervention, resulting in 72 participants who received the study intervention.

Participant milestones

Measure	Lamotrigine Participants who received lamotrigine 7.0 mg/kg tablets or chewable tablets daily, administered in 2 equally divided doses	Oxcarbazepine Participants who received oxcarbazepine 25 mg/kg tablets or liquid daily, administered in 2 equally divided doses	Levetiracetam Participants who received levetiracetam 30 mg/kg tablet or liquid daily, administered in 2 equally divided doses
Overall Study STARTED	24	27	21
Overall Study COMPLETED	17	24	14
Overall Study NOT COMPLETED	7	3	7

Reasons for withdrawal

Measure	Lamotrigine Participants who received lamotrigine 7.0 mg/kg tablets or chewable tablets daily, administered in 2 equally divided doses	Oxcarbazepine Participants who received oxcarbazepine 25 mg/kg tablets or liquid daily, administered in 2 equally divided doses	Levetiracetam Participants who received levetiracetam 30 mg/kg tablet or liquid daily, administered in 2 equally divided doses
Overall Study Lost to Follow-up	0	0	1
Overall Study Study ended before endpoint reached	7	3	6

Baseline Characteristics

Cognitive AED Outcomes in Pediatric Localization Related Epilepsy (COPE)

Baseline characteristics by cohort

Measure	Lamotrigine n=24 Participants Participants who received lamotrigine 7.0 mg/kg tablets or chewable tablets daily, administered in 2 equally divided doses	Oxcarbazepine n=27 Participants Participants who received oxcarbazepine 25 mg/kg tablets or liquid daily, administered in 2 equally divided doses	Levetiracetam n=21 Participants Participants who received levetiracetam 30 mg/kg tablet or liquid daily, administered in 2 equally divided doses	Total n=72 Participants Total of all reporting groups
Age, Categorical <=18 years	24 Participants n=5 Participants	27 Participants n=7 Participants	21 Participants n=5 Participants	72 Participants n=4 Participants
Age, Categorical Between 18 and 65 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Age, Continuous	8.6 years STANDARD_DEVIATION 2.0 • n=5 Participants	8.6 years STANDARD_DEVIATION 2.4 • n=7 Participants	9.1 years STANDARD_DEVIATION 2.1 • n=5 Participants	8.7 years STANDARD_DEVIATION 2.8 • n=4 Participants
Sex: Female, Male Female	13 Participants n=5 Participants	12 Participants n=7 Participants	11 Participants n=5 Participants	36 Participants n=4 Participants
Sex: Female, Male Male	11 Participants n=5 Participants	15 Participants n=7 Participants	10 Participants n=5 Participants	36 Participants n=4 Participants
Region of Enrollment United States	24 Participants n=5 Participants	27 Participants n=7 Participants	21 Participants n=5 Participants	72 Participants n=4 Participants

PRIMARY outcome

Timeframe: Baseline, Month 6

Population: The analysis includes participants who completed the assessment at the specified study visit. Some participants attended a study visit but did not complete the CPT-II.

The Conners' Continuous Performance Test II (CPT-II) is a measure of sustained attention. Letters are individually presented on a computer screen, and participants are instructed to press the space bar when they are presented with any letter except the letter "X". For children younger than 6 years of age at enrollment, the Kiddie CPT will be used in which the child is instructed to press the space bar every time the ball appears on the screen. The outcome measure is a confidence index representing the probability that the respondent has a clinically relevant problem in sustained attention. Possible scores range from 0 to 100. Scores between 40 and 60 are considered inconclusive while scores above 60 indicate that the child exhibits inattentiveness.

Outcome measures

Measure	Lamotrigine n=24 Participants Participants who received lamotrigine 7.0 mg/kg tablets or chewable tablets daily, administered in 2 equally divided doses	Oxcarbazepine n=26 Participants Participants who received oxcarbazepine 25 mg/kg tablets or liquid daily, administered in 2 equally divided doses	Levetiracetam n=20 Participants Participants who received levetiracetam 30 mg/kg tablet or liquid daily, administered in 2 equally divided doses
Conners' Continuous Performance Test II (CPT-II) Confidence Index Baseline	58.4 Confidence Index Standard Deviation 20.0	56.7 Confidence Index Standard Deviation 21.6	56.9 Confidence Index Standard Deviation 23.9
Conners' Continuous Performance Test II (CPT-II) Confidence Index After 6 months of treatment	58.1 Confidence Index Standard Deviation 23.2	54.2 Confidence Index Standard Deviation 21.7	54.0 Confidence Index Standard Deviation 24.4

SECONDARY outcome

Timeframe: Baseline, Month 6

Population: The analysis includes participants who completed the assessment at the specified study visit. Some participants attended a study visit but did not complete the Child Behavior Checklist.

The Child Behavior Checklist is a measure of specific behavioral and emotional problems are rated by the child's parent or guardian. The Child Behavior Checklist examines three domains (Social Functioning, Mood and Anxiety Symptoms, and Externalizing Symptoms) by assessing 118 problem items that describe specific behavioral and emotional problems. Respondents indicate how accurately the statements describe the child by selecting from options on a 3-point Likert-type scale (0=Not True, 1= Somewhat or Sometimes True, or 2=Very True or Often True). Total raw scores are converted to t-scores with a mean of 50 and standard deviation of 10. A t-score of 67 or greater is considered to be in the clinical range for problematic behavior.

Outcome measures

Measure	Lamotrigine n=22 Participants Participants who received lamotrigine 7.0 mg/kg tablets or chewable tablets daily, administered in 2 equally divided doses	Oxcarbazepine n=26 Participants Participants who received oxcarbazepine 25 mg/kg tablets or liquid daily, administered in 2 equally divided doses	Levetiracetam n=18 Participants Participants who received levetiracetam 30 mg/kg tablet or liquid daily, administered in 2 equally divided doses
Child Behavior Checklist Baseline	37.6 t-scores Standard Deviation 9.9	39.8 t-scores Standard Deviation 10.2	38.2 t-scores Standard Deviation 10.3
Child Behavior Checklist After 6 months of treatment	37.5 t-scores Standard Deviation 9.6	36.7 t-scores Standard Deviation 11.1	33.3 t-scores Standard Deviation 9.1

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline, Month 3, Month 6

Population: The analysis includes participants who completed the assessment at the specified study visit. Some participants attended a study visit but did not complete the WISC-IV.

Coding and Symbol Search subtests from the Wechsler Intelligence Scale for Children (WISC)-IV are measures of processing speed and combine to form the Processing Speed Index. Processing speed refers to how quickly the child understands and responds to information. Coding presents children with a row of boxes containing a numeral in the top line and a symbol in the bottom line with the task of copying the symbol corresponding to each numeral as quickly as possible in 120 seconds. In Symbol Search, children are given rows of symbols and target symbols and are asked to mark whether or not the target symbols appear in each row as quickly as possible during 120 seconds. Composite scores compare the test-taker to peers with a mean score of 100 and a standard deviation of 15. Possible scores range from 40 to 160 with higher scores indicating increased processing speeds. Scores between 85 and 115 are considered average, with 2/3 of test takers falling between these values.

Outcome measures

Measure	Lamotrigine n=23 Participants Participants who received lamotrigine 7.0 mg/kg tablets or chewable tablets daily, administered in 2 equally divided doses	Oxcarbazepine n=27 Participants Participants who received oxcarbazepine 25 mg/kg tablets or liquid daily, administered in 2 equally divided doses	Levetiracetam n=19 Participants Participants who received levetiracetam 30 mg/kg tablet or liquid daily, administered in 2 equally divided doses
Wechsler Intelligence Scale for Children-IV Processing Speed Baseline	87.8 units on a scale Standard Deviation 12.1	97.9 units on a scale Standard Deviation 15.5	102.1 units on a scale Standard Deviation 12.3
Wechsler Intelligence Scale for Children-IV Processing Speed After 3 months of treatment	95.7 units on a scale Standard Deviation 16.7	90.4 units on a scale Standard Deviation 12.7	96.9 units on a scale Standard Deviation 14.0
Wechsler Intelligence Scale for Children-IV Processing Speed After 6 months of treatment	97.3 units on a scale Standard Deviation 20.8	101.22 units on a scale Standard Deviation 19.1	102.6 units on a scale Standard Deviation 13.8

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline, Month 6

Population: The analysis includes participants who completed the assessment at the specified study visit. Some participants attended a study visit but did not complete the Story Memory measurement.

Story Memory will be measured at baseline with the Children's Memory Scale (CMS) and then with the Wide Range Assessment of Memory and Learning-2 (WRAML-2) at the 6 month follow up visit. Two different tests are used to avoid practice effects in memory assessment associated with repeated assessments using the same stimulus material. The Story Memory sub-test of the CMS and the WRAML-2 Story Memory are measures of prose passage recall. Stories are read to the subject for recall, with different stories presented based upon participant age. Scores are converted to percentile ranks for both measurements of story memory. Possible scores can fall between the 1st and 99th percentile and higher values indicate better performance with story recall. Values between the 9th and 25 percentiles are considered "low average", values between the 25th and 75th percentiles are "average", while values between the 75th and 91st percentile are "high average".

Outcome measures

Measure	Lamotrigine n=22 Participants Participants who received lamotrigine 7.0 mg/kg tablets or chewable tablets daily, administered in 2 equally divided doses	Oxcarbazepine n=26 Participants Participants who received oxcarbazepine 25 mg/kg tablets or liquid daily, administered in 2 equally divided doses	Levetiracetam n=20 Participants Participants who received levetiracetam 30 mg/kg tablet or liquid daily, administered in 2 equally divided doses
Story Memory Baseline (CMS)	29.6 percentiles Standard Deviation 16.2	31.2 percentiles Standard Deviation 17.0	29.4 percentiles Standard Deviation 12.2
Story Memory After 6 months of treatment (WRAML-2)	23.1 percentiles Standard Deviation 13.9	26.1 percentiles Standard Deviation 13.7	26.5 percentiles Standard Deviation 9.3

OTHER_PRE_SPECIFIED outcome

Timeframe: Month 3, Month 6

Population: The analysis includes participants who completed the assessment at the specified study visit. Participants who were 8 years old or older were eligible to complete the Symbol Digit Modalities Test.

Symbol Digit Modalities Test (SDMT) is a test of graphomotor speed using numbers as the response rather than copying symbols, and is timed at 90 seconds. The SDMT is designed for people who are 8 years of age and older and detects brain dysfunction as well as measures function over time. Possible total scores range from 0 to 110; where 110 indicates that all values were entered within the 90 second limit. An increase between initial and retest scores indicates that the respondent is correctly matching numbers to symbols at a faster speed. The SDMT was administered at the Month 3 and Month 6 visits for this study.

Outcome measures

Measure	Lamotrigine n=10 Participants Participants who received lamotrigine 7.0 mg/kg tablets or chewable tablets daily, administered in 2 equally divided doses	Oxcarbazepine n=15 Participants Participants who received oxcarbazepine 25 mg/kg tablets or liquid daily, administered in 2 equally divided doses	Levetiracetam n=9 Participants Participants who received levetiracetam 30 mg/kg tablet or liquid daily, administered in 2 equally divided doses
Symbol Digit Modalities Test After 3 months of treatment	25.9 number of correct responses Standard Deviation 10.3	28.5 number of correct responses Standard Deviation 10.3	23.0 number of correct responses Standard Deviation 9.4
Symbol Digit Modalities Test After 6 months of treatment	26.4 number of correct responses Standard Deviation 11.3	30.4 number of correct responses Standard Deviation 12.3	28.3 number of correct responses Standard Deviation 8.6

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline, Month 6

Population: The analysis includes participants who completed the assessment at the specified study visit. Some participants attended a study visit but did not complete the Grooved Pegboard task.

The Grooved Pegboard assesses fine motor speed and dexterity. The participant fits keyhole-shaped pegs into similarly shaped holes on a square board. The pegs, which have an edge along one side, must be rotated to match the holes before they can be inserted. The scores represent the number of seconds it took for the participant to correctly insert the pegs into the require number of grooves, using their dominant hand.

Outcome measures

Measure	Lamotrigine n=21 Participants Participants who received lamotrigine 7.0 mg/kg tablets or chewable tablets daily, administered in 2 equally divided doses	Oxcarbazepine n=26 Participants Participants who received oxcarbazepine 25 mg/kg tablets or liquid daily, administered in 2 equally divided doses	Levetiracetam n=20 Participants Participants who received levetiracetam 30 mg/kg tablet or liquid daily, administered in 2 equally divided doses
Grooved Pegboard Baseline	99.9 Seconds Standard Deviation 24.8	96.3 Seconds Standard Deviation 24.0	114.2 Seconds Standard Deviation 36.2
Grooved Pegboard After 6 months of treatment	90.3 Seconds Standard Deviation 34.7	90.1 Seconds Standard Deviation 24.2	94.9 Seconds Standard Deviation 19.7

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline, Month 3, Month 6

Population: The analysis includes participants who completed the assessment at the specified study visit. Some participants attended a study visit but did not complete the C-SSRS.

Suicidal behaviors and suicidal ideation were assessed through an interview using the Columbia-Suicide Severity Rating Scale (C-SSRS). The C-SSRS guides interviewers to ask a series of simple questions in order to identify people at risk for suicide, as well as the severity and urgency of suicidal thoughts and behaviors. The Children's Baseline/Screening C-SSRS was used at the initial study visit while the Children's Since Last Visit C-SSRS was used for subsequent study visits. Any responses of "yes" to the C-SSRS questions are considered a positive response, indicating that the participant is experiencing thoughts of suicide or has exhibited suicidal behaviors.

Outcome measures

Measure	Lamotrigine n=23 Participants Participants who received lamotrigine 7.0 mg/kg tablets or chewable tablets daily, administered in 2 equally divided doses	Oxcarbazepine n=27 Participants Participants who received oxcarbazepine 25 mg/kg tablets or liquid daily, administered in 2 equally divided doses	Levetiracetam n=20 Participants Participants who received levetiracetam 30 mg/kg tablet or liquid daily, administered in 2 equally divided doses
The Number of Participants With a Positive Response on the Columbia-Suicide Severity Rating Scale (C-SSRS) Baseline	0 Participants	0 Participants	0 Participants
The Number of Participants With a Positive Response on the Columbia-Suicide Severity Rating Scale (C-SSRS) After 3 months of treatment	0 Participants	0 Participants	0 Participants
The Number of Participants With a Positive Response on the Columbia-Suicide Severity Rating Scale (C-SSRS) After 6 months of treatment	0 Participants	0 Participants	0 Participants

OTHER_PRE_SPECIFIED outcome

Timeframe: 6 months

Population: As this study was terminated early, the scoring algorithm was not programmed for this outcome measure.

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline, Month 3, Month 6

Population: The analysis includes participants who completed the assessment at the specified study visit. Some participants attended a study visit but did not complete the Affective Reactivity Scale.

The Affective Reactivity Scale is a 7-item survey completed by the child participants which asks questions concerning their level of agreement with statements about anger and irritability. Respondents select between "not true" (scored as 0), "somewhat true" (scored as 1), and "certainly true (scored as 2). Total scores range from 0 to 14 with higher values indicating increased feelings of annoyance and anger.

Outcome measures

Measure	Lamotrigine n=24 Participants Participants who received lamotrigine 7.0 mg/kg tablets or chewable tablets daily, administered in 2 equally divided doses	Oxcarbazepine n=27 Participants Participants who received oxcarbazepine 25 mg/kg tablets or liquid daily, administered in 2 equally divided doses	Levetiracetam n=21 Participants Participants who received levetiracetam 30 mg/kg tablet or liquid daily, administered in 2 equally divided doses
Affective Reactivity Scale After 6 months of treatment	8.8 units on a scale Standard Deviation 3.0	8.2 units on a scale Standard Deviation 2.7	10.3 units on a scale Standard Deviation 3.2
Affective Reactivity Scale Baseline	9.2 units on a scale Standard Deviation 2.5	8.6 units on a scale Standard Deviation 2.7	8.6 units on a scale Standard Deviation 2.2
Affective Reactivity Scale After 3 months of treatment	8.8 units on a scale Standard Deviation 2.5	8.5 units on a scale Standard Deviation 2.0	10.3 units on a scale Standard Deviation 3.1

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline, Month 6

Population: The analysis includes participants who completed the assessment at the specified study visit. This survey was completed by children aged 10 and older.

The Pediatric Neuro-QOL is a Quality of Life instrument developed in conjunction with NIH with a pediatric specific form utilized in this protocol. Pediatric Neuro-QOL assesses the domains of Anger, Anxiety, Cognition, Depression, Fatigue, Pain, Social Relations, and Stigma. Each domain has 8 to 10 items and respondents indicate how often they experienced feelings and circumstances related to each domain on a scale of 1 to 5 (such as 1=never, 2=almost never, 3=sometimes, 4=often, 5=almost always). Higher values indicate increased difficulty for most of the scales but this pattern is reversed for two of the domains. Raw scores are rescaled to standardized scores with a mean of 50 and a standard deviation of 10. Higher values for the standardized scores indicate more problematic characteristics while scores below 50 indicate that the child is experiencing less trouble in the domains measured by the Pediatric Neuro-QOL.

Outcome measures

Measure	Lamotrigine n=14 Participants Participants who received lamotrigine 7.0 mg/kg tablets or chewable tablets daily, administered in 2 equally divided doses	Oxcarbazepine n=15 Participants Participants who received oxcarbazepine 25 mg/kg tablets or liquid daily, administered in 2 equally divided doses	Levetiracetam n=11 Participants Participants who received levetiracetam 30 mg/kg tablet or liquid daily, administered in 2 equally divided doses
Pediatric Neuro-QOL Score Baseline	37.0 t-scores Standard Deviation 6.0	39.9 t-scores Standard Deviation 9.6	38.8 t-scores Standard Deviation 5.6
Pediatric Neuro-QOL Score After 6 months of treatment	36.7 t-scores Standard Deviation 8.2	35.2 t-scores Standard Deviation 5.2	36.9 t-scores Standard Deviation 5.3

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline, Month 6

Population: The analysis includes participants who completed the assessment at the specified study visit. Some parents attended a study visit but did not complete the PSI-4-SF.

The Parenting Stress Inventory-4-Short Form is a 36 item questionnaire, completed by the parent/guardian, designed to evaluate parenting and family characteristics based upon child characteristics (behavioral and emotional problems), parent characteristics, and situational/demographic life stress. Respondents indicate the degree to which they agree with a variety of statements by selecting 1=strongly agree, 2=agree, 3=not sure, 4=disagree, or 5=strongly disagree. Raw scores range from 36 to 180 and higher scores are associated with higher parental stress.

Outcome measures

Measure	Lamotrigine n=22 Participants Participants who received lamotrigine 7.0 mg/kg tablets or chewable tablets daily, administered in 2 equally divided doses	Oxcarbazepine n=22 Participants Participants who received oxcarbazepine 25 mg/kg tablets or liquid daily, administered in 2 equally divided doses	Levetiracetam n=20 Participants Participants who received levetiracetam 30 mg/kg tablet or liquid daily, administered in 2 equally divided doses
Parenting Stress Inventory Short Form (PSI-4-SF) Baseline	138.2 units on a scale Standard Deviation 21.0	138.3 units on a scale Standard Deviation 17.5	143.9 units on a scale Standard Deviation 20.4
Parenting Stress Inventory Short Form (PSI-4-SF) After 6 months of treatment	147.4 units on a scale Standard Deviation 20.9	137.6 units on a scale Standard Deviation 24.3	146.8 units on a scale Standard Deviation 22.3

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline, Month 6

Population: The analysis includes participants who completed the assessment at the specified study visit. Some parents attended a study visit but did not complete the Pediatric Inventory for Parents.

The Pediatric Inventory for Parents consists of 42 items involving communication, medical care, emotional disturbance, and change in role function. Parents respond to a list of difficult events (such as "difficulty sleeping") that are often experienced by parents of children who are seriously ill. Parents indicated how frequently an event occurred by selecting 1=Never, 2=Rarely, 3=Sometimes, 4=Often, or 5=Very often. Raw score values range from 4 to 210 with higher scores indicating increased frequency of difficult events.

Outcome measures

Measure	Lamotrigine n=24 Participants Participants who received lamotrigine 7.0 mg/kg tablets or chewable tablets daily, administered in 2 equally divided doses	Oxcarbazepine n=25 Participants Participants who received oxcarbazepine 25 mg/kg tablets or liquid daily, administered in 2 equally divided doses	Levetiracetam n=21 Participants Participants who received levetiracetam 30 mg/kg tablet or liquid daily, administered in 2 equally divided doses
Pediatric Inventory for Parents Baseline	93.0 units on a scale Standard Deviation 21.5	98.4 units on a scale Standard Deviation 33.2	91.1 units on a scale Standard Deviation 29.9
Pediatric Inventory for Parents After 6 months of treatment	74.2 units on a scale Standard Deviation 20.3	76.5 units on a scale Standard Deviation 32.0	74.8 units on a scale Standard Deviation 17.6

Adverse Events

Lamotrigine

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Oxcarbazepine

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Levetiracetam

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Adverse event data not reported

Additional Information

David Loring, PhD

Emory University

Phone: 404-778-5943

Email: dloring@emory.edu

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place