Trial Outcomes & Findings for Continued Anticonvulsants After Resolution of Neonatal Seizures: a Patient-centered Comparative Effectiveness Study (NCT NCT02789176)

Last Updated: 2020-12-04

Results Overview

The Warner Initial Developmental Evaluation of Adaptive and Functional Skills (WIDEA FS) allowed us to compare the functional development between newborns who received short duration phenobarbital treatment and prolonged phenobarbital treatment. There were 50 questions with response options of 1(Never) to 4(all the time). WIDEA range was on a scale from 50-200 (At 24 months, the normal population mean score is 172±10).The higher the score the better the child's developmental function. Mean scores were calculated using data from any participant who completed surveys at 24 months.

Recruitment status

COMPLETED

Target enrollment

303 participants

Primary outcome timeframe

24 months

Results posted on

2020-12-04

Participant Flow

Participant milestones

Participant milestones
Measure	Outpatient Enrollees - Maintain Anti-Seizure Medicine This is a cohort of subjects who were previously enrolled in the Neonatal Seizure Registry and had been discharged from the Neonatal Intensive Care Unit (NICU) on anti-seizure medicine. They were asked to take part in all prospective follow up surveys regarding development, epilepsy, and family impact at 12, 18, \& 24 months of age.	Outpatient Enrollees- Discontinue Anti-Seizure Medicine This is a cohort of subjects who were previously enrolled in the Neonatal Seizure Registry and had been discharged from the Neonatal Intensive Care Unit (NICU) off anti-seizure medicine. They were asked to take part in all prospective follow up surveys regarding development, epilepsy, and family impact at 12, 18, \& 24 months of age.	Inpatient Enrollees - Maintain Anti-Seizure Medicine This is a cohort of subjects who were enrolled in the study prior to discharge from the NICU and had been discharged on anti-seizure medicine. They were asked to return to the hospital for a 1 hour EEG to monitor brain activity between 2-4 months of age, and complete surveys regarding development, epilepsy, and family impact prior to discharge from the NICU and at 12, 18, \& 24 months of age.	Inpatient Enrollees - Discontinue Anti-Seizure Medicine This is a cohort of subjects who were enrolled in the study prior to discharge from the NICU and had been discharged off anti-seizure medicine. They were asked to return to the hospital for a 1 hour EEG to monitor brain activity between 2-4 months of age, and complete surveys regarding development, epilepsy, and family impact prior to discharge from the NICU and at 12, 18, \& 24 months of age.
Overall Study STARTED	99	55	95	54
Overall Study COMPLETED	91	53	85	53
Overall Study NOT COMPLETED	8	2	10	1

Reasons for withdrawal

Reasons for withdrawal
Measure	Outpatient Enrollees - Maintain Anti-Seizure Medicine This is a cohort of subjects who were previously enrolled in the Neonatal Seizure Registry and had been discharged from the Neonatal Intensive Care Unit (NICU) on anti-seizure medicine. They were asked to take part in all prospective follow up surveys regarding development, epilepsy, and family impact at 12, 18, \& 24 months of age.	Outpatient Enrollees- Discontinue Anti-Seizure Medicine This is a cohort of subjects who were previously enrolled in the Neonatal Seizure Registry and had been discharged from the Neonatal Intensive Care Unit (NICU) off anti-seizure medicine. They were asked to take part in all prospective follow up surveys regarding development, epilepsy, and family impact at 12, 18, \& 24 months of age.	Inpatient Enrollees - Maintain Anti-Seizure Medicine This is a cohort of subjects who were enrolled in the study prior to discharge from the NICU and had been discharged on anti-seizure medicine. They were asked to return to the hospital for a 1 hour EEG to monitor brain activity between 2-4 months of age, and complete surveys regarding development, epilepsy, and family impact prior to discharge from the NICU and at 12, 18, \& 24 months of age.	Inpatient Enrollees - Discontinue Anti-Seizure Medicine This is a cohort of subjects who were enrolled in the study prior to discharge from the NICU and had been discharged off anti-seizure medicine. They were asked to return to the hospital for a 1 hour EEG to monitor brain activity between 2-4 months of age, and complete surveys regarding development, epilepsy, and family impact prior to discharge from the NICU and at 12, 18, \& 24 months of age.
Overall Study Death	0	0	3	0
Overall Study Withdrawal by Subject	0	0	1	0
Overall Study Lost to Follow-up	8	2	6	1

Baseline Characteristics

Not all subjects completed all the time points and survey questions. Therefore, the number analyzed in the rows may vary.

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Outpatient Enrollees - Maintatin Anti-Seizure Medicine n=99 Participants This is a cohort of subjects who were previously enrolled in the Neonatal Seizure Registry and had been discharged from the Neonatal Intensive Care Unit (NICU) on anti-seizure medicine. They were asked to take part in all prospective follow up surveys regarding development, epilepsy, and family impact at 12, 18, \& 24 months of age.	Outpatient Enrollees - Discontinue Anti-Seizure Medicine n=55 Participants This is a cohort of subjects who were previously enrolled in the Neonatal Seizure Registry and had been discharged from the Neonatal Intensive Care Unit (NICU) off anti-seizure medicine. They were asked to take part in all prospective follow up surveys regarding development, epilepsy, and family impact at 12, 18, \& 24 months of age.	Inpatient Enrollees - Maintain Anti-Seizure Medicine n=95 Participants This is a cohort of subjects who were enrolled in the study prior to discharge from the NICU and had been discharged on anti-seizure medicine. They were asked to return to the hospital for a 1 hour EEG to monitor brain activity between 2-4 months of age, and complete surveys regarding development, epilepsy, and family impact prior to discharge from the NICU and at 12, 18, \& 24 months of age.	Inpatient Enrollees - Discontinue Anti-Seizure Medicine n=54 Participants This is a cohort of subjects who were enrolled in the study prior to discharge from the NICU and had been discharged off anti-seizure medicine. They were asked to return to the hospital for a 1 hour EEG to monitor brain activity between 2-4 months of age, and complete surveys regarding development, epilepsy, and family impact prior to discharge from the NICU and at 12, 18, \& 24 months of age.	Total n=303 Participants Total of all reporting groups
Age, Continuous	23.89 Months STANDARD_DEVIATION 0.76 • n=92 Participants • Not all subjects completed all the time points and survey questions. Therefore, the number analyzed in the rows may vary.	23.94 Months STANDARD_DEVIATION 0.76 • n=53 Participants • Not all subjects completed all the time points and survey questions. Therefore, the number analyzed in the rows may vary.	23.65 Months STANDARD_DEVIATION 0.56 • n=79 Participants • Not all subjects completed all the time points and survey questions. Therefore, the number analyzed in the rows may vary.	23.97 Months STANDARD_DEVIATION 0.76 • n=49 Participants • Not all subjects completed all the time points and survey questions. Therefore, the number analyzed in the rows may vary.	23.84 Months STANDARD_DEVIATION 0.72 • n=273 Participants • Not all subjects completed all the time points and survey questions. Therefore, the number analyzed in the rows may vary.
Sex: Female, Male Female	47 Participants n=99 Participants	26 Participants n=55 Participants	36 Participants n=95 Participants	24 Participants n=54 Participants	133 Participants n=303 Participants
Sex: Female, Male Male	52 Participants n=99 Participants	29 Participants n=55 Participants	59 Participants n=95 Participants	30 Participants n=54 Participants	170 Participants n=303 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=99 Participants	0 Participants n=55 Participants	1 Participants n=95 Participants	1 Participants n=54 Participants	2 Participants n=303 Participants
Race (NIH/OMB) Asian	6 Participants n=99 Participants	3 Participants n=55 Participants	5 Participants n=95 Participants	6 Participants n=54 Participants	20 Participants n=303 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=99 Participants	0 Participants n=55 Participants	2 Participants n=95 Participants	0 Participants n=54 Participants	2 Participants n=303 Participants
Race (NIH/OMB) Black or African American	12 Participants n=99 Participants	11 Participants n=55 Participants	7 Participants n=95 Participants	6 Participants n=54 Participants	36 Participants n=303 Participants
Race (NIH/OMB) White	69 Participants n=99 Participants	36 Participants n=55 Participants	59 Participants n=95 Participants	28 Participants n=54 Participants	192 Participants n=303 Participants
Race (NIH/OMB) More than one race	5 Participants n=99 Participants	0 Participants n=55 Participants	3 Participants n=95 Participants	2 Participants n=54 Participants	10 Participants n=303 Participants
Race (NIH/OMB) Unknown or Not Reported	7 Participants n=99 Participants	5 Participants n=55 Participants	18 Participants n=95 Participants	11 Participants n=54 Participants	41 Participants n=303 Participants

PRIMARY outcome

Timeframe: 24 months

Outcome measures

Outcome measures
Measure	Outpatient Enrollees - Maintain Anti-Seizure Medicine n=90 Participants This is a cohort of subjects who were previously enrolled in the Neonatal Seizure Registry and had been discharged from the Neonatal Intensive Care Unit (NICU) on anti-seizure medicine. They were asked to take part in all prospective follow up surveys regarding development, epilepsy, and family impact at 12, 18, \& 24 months of age.	Outpatient Enrollees - Discontinue Anti-Seizure Medicine n=52 Participants This is a cohort of subjects who were previously enrolled in the Neonatal Seizure Registry and had been discharged from the Neonatal Intensive Care Unit (NICU) off anti-seizure medicine. They were asked to take part in all prospective follow up surveys regarding development, epilepsy, and family impact at 12, 18, \& 24 months of age.	Inpatient Enrollees - Maintain Anti-Seizure Medicine n=79 Participants This is a cohort of subjects who were enrolled in the study prior to discharge from the NICU and had been discharged on anti-seizure medicine. They were asked to return to the hospital for a 1 hour EEG to monitor brain activity between 2-4 months of age, and complete surveys regarding development, epilepsy, and family impact prior to discharge from the NICU and at 12, 18, \& 24 months of age.	Inpatient Enrollees - Discontinue Anti-Seizure Medicine n=49 Participants This is a cohort of subjects who were enrolled in the study prior to discharge from the NICU and had been discharged off anti-seizure medicine. They were asked to return to the hospital for a 1 hour EEG to monitor brain activity between 2-4 months of age, and complete surveys regarding development, epilepsy, and family impact prior to discharge from the NICU and at 12, 18, \& 24 months of age.
WIDEA Neurodevelopmental Outcome Score	149.04 score on a scale Standard Deviation 34.55	162.46 score on a scale Standard Deviation 25.94	148.80 score on a scale Standard Deviation 33.52	151.89 score on a scale Standard Deviation 33.24

PRIMARY outcome

Timeframe: 24 months

Population: Participants analyzed reflect the number of participants who completed the 24 month follow-up survey. Also one participant did not have data for epilepsy diagnosis

The diagnosis of epilepsy and the details of seizure types and frequencies were determined by telephone interview with the parent and corroborated by medical record review.

Outcome measures

Outcome measures
Measure	Outpatient Enrollees - Maintain Anti-Seizure Medicine n=90 Participants This is a cohort of subjects who were previously enrolled in the Neonatal Seizure Registry and had been discharged from the Neonatal Intensive Care Unit (NICU) on anti-seizure medicine. They were asked to take part in all prospective follow up surveys regarding development, epilepsy, and family impact at 12, 18, \& 24 months of age.	Outpatient Enrollees - Discontinue Anti-Seizure Medicine n=53 Participants This is a cohort of subjects who were previously enrolled in the Neonatal Seizure Registry and had been discharged from the Neonatal Intensive Care Unit (NICU) off anti-seizure medicine. They were asked to take part in all prospective follow up surveys regarding development, epilepsy, and family impact at 12, 18, \& 24 months of age.	Inpatient Enrollees - Maintain Anti-Seizure Medicine n=85 Participants This is a cohort of subjects who were enrolled in the study prior to discharge from the NICU and had been discharged on anti-seizure medicine. They were asked to return to the hospital for a 1 hour EEG to monitor brain activity between 2-4 months of age, and complete surveys regarding development, epilepsy, and family impact prior to discharge from the NICU and at 12, 18, \& 24 months of age.	Inpatient Enrollees - Discontinue Anti-Seizure Medicine n=53 Participants This is a cohort of subjects who were enrolled in the study prior to discharge from the NICU and had been discharged off anti-seizure medicine. They were asked to return to the hospital for a 1 hour EEG to monitor brain activity between 2-4 months of age, and complete surveys regarding development, epilepsy, and family impact prior to discharge from the NICU and at 12, 18, \& 24 months of age.
Number of Participants With Post-neonatal Epilepsy	14 Participants	2 Participants	11 Participants	10 Participants

SECONDARY outcome

Timeframe: length of stay, measured in days, will be recorded during a chart review when the child is 12 months of age

Evaluation of medication exposure (dose and duration) during the admission as a predictor of the number of days the infant requires care (length of stay)

Outcome measures

Outcome measures
Measure	Outpatient Enrollees - Maintain Anti-Seizure Medicine n=91 Participants This is a cohort of subjects who were previously enrolled in the Neonatal Seizure Registry and had been discharged from the Neonatal Intensive Care Unit (NICU) on anti-seizure medicine. They were asked to take part in all prospective follow up surveys regarding development, epilepsy, and family impact at 12, 18, \& 24 months of age.	Outpatient Enrollees - Discontinue Anti-Seizure Medicine n=53 Participants This is a cohort of subjects who were previously enrolled in the Neonatal Seizure Registry and had been discharged from the Neonatal Intensive Care Unit (NICU) off anti-seizure medicine. They were asked to take part in all prospective follow up surveys regarding development, epilepsy, and family impact at 12, 18, \& 24 months of age.	Inpatient Enrollees - Maintain Anti-Seizure Medicine n=85 Participants This is a cohort of subjects who were enrolled in the study prior to discharge from the NICU and had been discharged on anti-seizure medicine. They were asked to return to the hospital for a 1 hour EEG to monitor brain activity between 2-4 months of age, and complete surveys regarding development, epilepsy, and family impact prior to discharge from the NICU and at 12, 18, \& 24 months of age.	Inpatient Enrollees - Discontinue Anti-Seizure Medicine n=53 Participants This is a cohort of subjects who were enrolled in the study prior to discharge from the NICU and had been discharged off anti-seizure medicine. They were asked to return to the hospital for a 1 hour EEG to monitor brain activity between 2-4 months of age, and complete surveys regarding development, epilepsy, and family impact prior to discharge from the NICU and at 12, 18, \& 24 months of age.
Length of Stay for the Neonatal Seizure Admission	15 number of days Interval 10.0 to 25.0	11 number of days Interval 7.0 to 19.0	17 number of days Interval 9.0 to 37.0	15 number of days Interval 9.0 to 31.0

SECONDARY outcome

Timeframe: 24 months

Population: Not all subjects completed every survey question, therefore some rows have different participants for the various outcome measures.

Surveys selected with the help of our Parent Partners were given at 12, 18, and 24 months to assess the impact of neonatal seizure treatment duration on parent and family quality of life and well-being. The 24 month data is presented, as they align with the primary outcome. The study team reviewed the HADS 24 month Anxiety and Depression Score range of possible scores from 0-21 (higher = more depressed/more anxious), the 24 month Transformed WHO Overall Quality of Life and General Health score range of scores 0-100 (higher=better quality of life), the 24 month Impact on Family Scale overall impact scale range from 15-60 (higher = more impact on family), the 24 month Post Traumatic Growth Inventory scale range from 0 -105 (higher = better/more growth), and the 24 month Impact of Events Scale-Revised scale range from 0 - 88 (higher score = worse impact).

Outcome measures

Outcome measures
Measure	Outpatient Enrollees - Maintain Anti-Seizure Medicine n=82 Participants This is a cohort of subjects who were previously enrolled in the Neonatal Seizure Registry and had been discharged from the Neonatal Intensive Care Unit (NICU) on anti-seizure medicine. They were asked to take part in all prospective follow up surveys regarding development, epilepsy, and family impact at 12, 18, \& 24 months of age.	Outpatient Enrollees - Discontinue Anti-Seizure Medicine n=50 Participants This is a cohort of subjects who were previously enrolled in the Neonatal Seizure Registry and had been discharged from the Neonatal Intensive Care Unit (NICU) off anti-seizure medicine. They were asked to take part in all prospective follow up surveys regarding development, epilepsy, and family impact at 12, 18, \& 24 months of age.	Inpatient Enrollees - Maintain Anti-Seizure Medicine n=70 Participants This is a cohort of subjects who were enrolled in the study prior to discharge from the NICU and had been discharged on anti-seizure medicine. They were asked to return to the hospital for a 1 hour EEG to monitor brain activity between 2-4 months of age, and complete surveys regarding development, epilepsy, and family impact prior to discharge from the NICU and at 12, 18, \& 24 months of age.	Inpatient Enrollees - Discontinue Anti-Seizure Medicine n=43 Participants This is a cohort of subjects who were enrolled in the study prior to discharge from the NICU and had been discharged off anti-seizure medicine. They were asked to return to the hospital for a 1 hour EEG to monitor brain activity between 2-4 months of age, and complete surveys regarding development, epilepsy, and family impact prior to discharge from the NICU and at 12, 18, \& 24 months of age.
Impact of Treatment Duration on Parent and Family Well-being 24 month HADS Depression Score	3.44 score on a scale Standard Deviation 3.01	2.92 score on a scale Standard Deviation 2.61	3.17 score on a scale Standard Deviation 2.97	3.72 score on a scale Standard Deviation 4.04
Impact of Treatment Duration on Parent and Family Well-being 24 month Post Traumatic Growth Inventory	59.5 score on a scale Standard Deviation 25.1	61.9 score on a scale Standard Deviation 25.3	61.7 score on a scale Standard Deviation 27.0	62.7 score on a scale Standard Deviation 25.0
Impact of Treatment Duration on Parent and Family Well-being 24 month Impact of Events Scale	15.1 score on a scale Standard Deviation 15.0	14.7 score on a scale Standard Deviation 13.6	13.8 score on a scale Standard Deviation 13.9	16.3 score on a scale Standard Deviation 15.0
Impact of Treatment Duration on Parent and Family Well-being 24 month HADS Anxiety Score	6.15 score on a scale Standard Deviation 4.20	5.30 score on a scale Standard Deviation 3.81	5.83 score on a scale Standard Deviation 3.79	6.84 score on a scale Standard Deviation 4.89
Impact of Treatment Duration on Parent and Family Well-being 24 month Transformed WHO Overall Quality of Life Score	76.09 score on a scale Standard Deviation 18.14	78.00 score on a scale Standard Deviation 16.67	76.67 score on a scale Standard Deviation 17.75	75.32 score on a scale Standard Deviation 20.97
Impact of Treatment Duration on Parent and Family Well-being 24 month Impact on Family Scale overall impact scale, 24 mo	28.78 score on a scale Standard Deviation 10.41	25.50 score on a scale Standard Deviation 9.26	28.30 score on a scale Standard Deviation 10.31	28.88 score on a scale Standard Deviation 11.42

Adverse Events

Outpatient Enrollees - Maintain Anti-Seizure Medicine

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Outpatient Enrollees - Discontinue Anti-Seizure Medicine

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Inpatient Enrollees - Maintain Anti-Seizure Medicine

Serious events: 0 serious events

Other events: 0 other events

Deaths: 3 deaths

Inpatient Enrollees -Discontinue Anti-Seizure Medicine

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

Stephanie Rau

University of Michigan

Phone: 734-232-8474

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place