Trial Outcomes & Findings for Non-Opiate Treatment After Prenatal Opiate Exposure to Prevent Postnatal Injury to the Young Brain (NCT NCT03396588)

Last Updated: 2025-05-23

Results Overview

The summary scores from the Neonatal Intensive Care Unit Network Neurobehavioral Scale (NNNS) give a measure of infant neurobehavior in the following areas (score range): habituation (1-9), regulation (2.20-7.50), attention (1.29-8.4), Handling (0-1), quality of movement (1.20-6.20), Non-optimal reflexes (0-12), Asymmetric reflexes (0-7), arousal (2.43-6.67), hypertonicity (0-8), hypotonicity (0-5.0), excitability (0-11), lethargy (0-11.0), and stress/abstinence (0-0.57). A higher score for each item means a higher level of the construct. For example, a higher score for hypertonicity means the infant is more hypertonic and higher score on hypotonicity means the infant is more hypotonic. No cut-off score published for normal or abnormal behavioral performance.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

120 participants

Primary outcome timeframe

Baseline (5-10 days post natal age) and one-month post-natal age (between 4-6 weeks of age), or at discharge, whichever comes first.

Results posted on

2025-05-23

Participant Flow

Participant milestones

Participant milestones
Measure	Clonidine Babies randomized to clonidine will receive 1mcg/kg/dose (with a dosing interval of 3 or 4 hours). Clonidine: 1mcg/kg/dose (with a dosing interval of 3 or 4 hours), increases by 25% of initial dose every 12-24 hrs. Decrease by 10% of max dose every 24 hrs.	Morphine Babies randomized to morphine will receive 0.06 mg/kg/dose (with a dosing interval of 3 or 4 hours). Morphine: Starting dose is 0.06 mg/kg/dose (every 3 or 4 hours), increases by 25% of initial dose every 12-24 hrs. Decrease by 10% of max dose every 24 hrs.
Overall Study STARTED	60	60
Overall Study COMPLETED	58	57
Overall Study NOT COMPLETED	2	3

Reasons for withdrawal

Reasons for withdrawal
Measure	Clonidine Babies randomized to clonidine will receive 1mcg/kg/dose (with a dosing interval of 3 or 4 hours). Clonidine: 1mcg/kg/dose (with a dosing interval of 3 or 4 hours), increases by 25% of initial dose every 12-24 hrs. Decrease by 10% of max dose every 24 hrs.	Morphine Babies randomized to morphine will receive 0.06 mg/kg/dose (with a dosing interval of 3 or 4 hours). Morphine: Starting dose is 0.06 mg/kg/dose (every 3 or 4 hours), increases by 25% of initial dose every 12-24 hrs. Decrease by 10% of max dose every 24 hrs.
Overall Study Physician Decision	2	3

Baseline Characteristics

Non-Opiate Treatment After Prenatal Opiate Exposure to Prevent Postnatal Injury to the Young Brain

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Clonidine n=60 Participants Babies randomized to clonidine will receive 1mcg/kg/dose (with a dosing interval of 3 or 4 hours). Clonidine: 1mcg/kg/dose (with a dosing interval of 3 or 4 hours), increases by 25% of initial dose every 12-24 hrs. Decrease by 10% of max dose every 24 hrs.	Morphine n=60 Participants Babies randomized to morphine will receive 0.06 mg/kg/dose (with a dosing interval of 3 or 4 hours). Morphine: Starting dose is 0.06 mg/kg/dose (every 3 or 4 hours), increases by 25% of initial dose every 12-24 hrs. Decrease by 10% of max dose every 24 hrs.	Total n=120 Participants Total of all reporting groups
Age, Categorical <=18 years	60 Participants n=5 Participants	60 Participants n=7 Participants	120 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	38.7 weeks STANDARD_DEVIATION 1.2 • n=5 Participants	38.3 weeks STANDARD_DEVIATION 1.3 • n=7 Participants	38.4 weeks STANDARD_DEVIATION 1.2 • n=5 Participants
Sex: Female, Male Female	23 Participants n=5 Participants	30 Participants n=7 Participants	53 Participants n=5 Participants
Sex: Female, Male Male	37 Participants n=5 Participants	30 Participants n=7 Participants	67 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants	4 Participants n=7 Participants	4 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	60 Participants n=5 Participants	56 Participants n=7 Participants	116 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) White	53 Participants n=5 Participants	52 Participants n=7 Participants	105 Participants n=5 Participants
Race (NIH/OMB) More than one race	6 Participants n=5 Participants	8 Participants n=7 Participants	14 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Region of Enrollment United States	60 participants n=5 Participants	60 participants n=7 Participants	120 participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline (5-10 days post natal age) and one-month post-natal age (between 4-6 weeks of age), or at discharge, whichever comes first.

Population: Some babies were unable to be assessed in certain domains and therefore were not included in the total analyzed for that domain.

Outcome measures

Outcome measures
Measure	Clonidine n=54 Participants Babies randomized to clonidine will receive 1mcg/kg/dose (with a dosing interval of 3 or 4 hours). Clonidine: 1mcg/kg/dose (with a dosing interval of 3 or 4 hours), increases by 25% of initial dose every 12-24 hrs. Decrease by 10% of max dose every 24 hrs.	Morphine n=51 Participants Babies randomized to morphine will receive 0.06 mg/kg/dose (with a dosing interval of 3 or 4 hours). Morphine: Starting dose is 0.06 mg/kg/dose (every 3 or 4 hours), increases by 25% of initial dose every 12-24 hrs. Decrease by 10% of max dose every 24 hrs.
Change in Neurobehavioral Performance Summary Scores From the Neonatal Intensive Care Unit Network Neurobehavioral Scale (NNNS) Habituation	0.5 score on a scale Interval -1.0 to 1.0	0.3 score on a scale Interval -1.0 to 1.0
Change in Neurobehavioral Performance Summary Scores From the Neonatal Intensive Care Unit Network Neurobehavioral Scale (NNNS) Attention	1.0 score on a scale Interval -0.1 to 2.0	0.6 score on a scale Interval 0.2 to 1.6
Change in Neurobehavioral Performance Summary Scores From the Neonatal Intensive Care Unit Network Neurobehavioral Scale (NNNS) Handling	-0.1 score on a scale Interval -0.4 to 0.1	0.1 score on a scale Interval 0.0 to 0.4
Change in Neurobehavioral Performance Summary Scores From the Neonatal Intensive Care Unit Network Neurobehavioral Scale (NNNS) Quality of movement	0.1 score on a scale Interval -0.3 to 0.8	0.0 score on a scale Interval -0.5 to 0.5
Change in Neurobehavioral Performance Summary Scores From the Neonatal Intensive Care Unit Network Neurobehavioral Scale (NNNS) Regulation	0.5 score on a scale Interval -0.5 to 1.3	-0.2 score on a scale Interval -0.8 to 0.2
Change in Neurobehavioral Performance Summary Scores From the Neonatal Intensive Care Unit Network Neurobehavioral Scale (NNNS) Non-optimal reflexes	-1.0 score on a scale Interval -2.5 to 1.0	-1.0 score on a scale Interval -2.0 to 1.0
Change in Neurobehavioral Performance Summary Scores From the Neonatal Intensive Care Unit Network Neurobehavioral Scale (NNNS) Asymmetry total/reflexes	0.0 score on a scale Interval 0.0 to 0.0	0.0 score on a scale Interval 0.0 to 0.0
Change in Neurobehavioral Performance Summary Scores From the Neonatal Intensive Care Unit Network Neurobehavioral Scale (NNNS) Arousal	-0.1 score on a scale Interval -0.6 to 0.3	0.4 score on a scale Interval 0.0 to 0.7
Change in Neurobehavioral Performance Summary Scores From the Neonatal Intensive Care Unit Network Neurobehavioral Scale (NNNS) Hypertonia	-1.0 score on a scale Interval -2.0 to 0.0	0.0 score on a scale Interval -1.0 to 0.0
Change in Neurobehavioral Performance Summary Scores From the Neonatal Intensive Care Unit Network Neurobehavioral Scale (NNNS) Hypotonia	0.0 score on a scale Interval 0.0 to 0.5	0.0 score on a scale Interval 0.0 to 0.0
Change in Neurobehavioral Performance Summary Scores From the Neonatal Intensive Care Unit Network Neurobehavioral Scale (NNNS) Excitability	-1.0 score on a scale Interval -3.0 to 1.0	1.0 score on a scale Interval -1.0 to 3.0
Change in Neurobehavioral Performance Summary Scores From the Neonatal Intensive Care Unit Network Neurobehavioral Scale (NNNS) Lethargy	0.0 score on a scale Interval -0.1 to 0.0	0.0 score on a scale Interval 0.0 to 0.1
Change in Neurobehavioral Performance Summary Scores From the Neonatal Intensive Care Unit Network Neurobehavioral Scale (NNNS) Stress abstinence	0.0 score on a scale Interval -0.1 to 0.0	0.0 score on a scale Interval 0.0 to 0.1

PRIMARY outcome

Timeframe: 6 months of life

Population: Participants may not have had the 6 month Bayley due to the participant being lost to follow up, or because of COVID-19 research restrictions.

Scores obtained Bayley Scales of Infant and Toddler Development Third Edition in the developmental domains of motor, cognitive, and language. This tool for measures of motor, cognitive, and language development is a series of standardized measurements and for each domain, the standardized scores have a mean of 100 and standard deviation of 15 with a range of 55-155 for cognitive and a range of 45-155 for language and motor (lower scores indicating greater impairment). Scores below 1 standard deviation (=or less than 84) is considered below normal. Scores above 1 standard deviation (over 115) represent higher than normal functioning in each domain. The score for each domain (motor, cognitive, and language functioning) represents the composite score.

Outcome measures

Outcome measures
Measure	Clonidine n=32 Participants Babies randomized to clonidine will receive 1mcg/kg/dose (with a dosing interval of 3 or 4 hours). Clonidine: 1mcg/kg/dose (with a dosing interval of 3 or 4 hours), increases by 25% of initial dose every 12-24 hrs. Decrease by 10% of max dose every 24 hrs.	Morphine n=38 Participants Babies randomized to morphine will receive 0.06 mg/kg/dose (with a dosing interval of 3 or 4 hours). Morphine: Starting dose is 0.06 mg/kg/dose (every 3 or 4 hours), increases by 25% of initial dose every 12-24 hrs. Decrease by 10% of max dose every 24 hrs.
Bayley Scales of Infant and Toddler Development Third Edition Cognitive	113.0 score on a scale Standard Deviation 12.8	111.8 score on a scale Standard Deviation 11.1
Bayley Scales of Infant and Toddler Development Third Edition Language	91.8 score on a scale Standard Deviation 13.4	87.7 score on a scale Standard Deviation 13.5
Bayley Scales of Infant and Toddler Development Third Edition Motor	102.4 score on a scale Standard Deviation 16.4	97.4 score on a scale Standard Deviation 12.3

PRIMARY outcome

Timeframe: 1 year of life

Population: Participants may not have had the 12 month Bayley due to the participant being lost to follow up, or because of COVID-19 research restrictions.

Outcome measures

Outcome measures
Measure	Clonidine n=19 Participants Babies randomized to clonidine will receive 1mcg/kg/dose (with a dosing interval of 3 or 4 hours). Clonidine: 1mcg/kg/dose (with a dosing interval of 3 or 4 hours), increases by 25% of initial dose every 12-24 hrs. Decrease by 10% of max dose every 24 hrs.	Morphine n=18 Participants Babies randomized to morphine will receive 0.06 mg/kg/dose (with a dosing interval of 3 or 4 hours). Morphine: Starting dose is 0.06 mg/kg/dose (every 3 or 4 hours), increases by 25% of initial dose every 12-24 hrs. Decrease by 10% of max dose every 24 hrs.
Bayley Scales of Infant and Toddler Development Third Edition Cognitive	98.2 score on a scale Standard Deviation 11.5	97.2 score on a scale Standard Deviation 10.8
Bayley Scales of Infant and Toddler Development Third Edition Language	91.8 score on a scale Standard Deviation 11.6	92.2 score on a scale Standard Deviation 12.2
Bayley Scales of Infant and Toddler Development Third Edition Motor	99.1 score on a scale Standard Deviation 12.2	96.2 score on a scale Standard Deviation 9.3

PRIMARY outcome

Timeframe: 2 years of life

Population: Participants may not have had the 24 month Bayley due to the participant being lost to follow up, or because of COVID-19 research restrictions.

Outcome measures

Outcome measures
Measure	Clonidine n=7 Participants Babies randomized to clonidine will receive 1mcg/kg/dose (with a dosing interval of 3 or 4 hours). Clonidine: 1mcg/kg/dose (with a dosing interval of 3 or 4 hours), increases by 25% of initial dose every 12-24 hrs. Decrease by 10% of max dose every 24 hrs.	Morphine n=8 Participants Babies randomized to morphine will receive 0.06 mg/kg/dose (with a dosing interval of 3 or 4 hours). Morphine: Starting dose is 0.06 mg/kg/dose (every 3 or 4 hours), increases by 25% of initial dose every 12-24 hrs. Decrease by 10% of max dose every 24 hrs.
Bayley Scales of Infant and Toddler Development Third Edition Cognitive	84.3 score on a scale Standard Deviation 6.7	81.1 score on a scale Standard Deviation 9.6
Bayley Scales of Infant and Toddler Development Third Edition Language	95.4 score on a scale Standard Deviation 9.4	86.2 score on a scale Standard Deviation 11.0
Bayley Scales of Infant and Toddler Development Third Edition Motor	97.6 score on a scale Standard Deviation 7.2	96.0 score on a scale Standard Deviation 9.8

PRIMARY outcome

Timeframe: 12 months of age

Population: ASQ-3 assessments were used for babies who were unable to have Bayley assessment performed due to COVID-19 research restrictions. The babies who had the Bayley did not have the ASQ.

The ASQ-3 is a developmental screening tool to assess developmental progress in children. Children are scored in the areas of communication, gross motor skills, fine motor skills, problem solving, and personal/social skills. The child's parent/guardian answers whether their child already does an activity (yes=10), sometimes does it (sometimes=5), or does not yet do it (not yet=0). The answers are then used to score each category. Each category is then broken down into whether the child falls above the cutoff (child development is on schedule), close to the cutoff (child development is slightly delayed and requires monitoring/intervention), or below the cutoff (delayed development and further assessment required).

Outcome measures

Outcome measures
Measure	Clonidine n=7 Participants Babies randomized to clonidine will receive 1mcg/kg/dose (with a dosing interval of 3 or 4 hours). Clonidine: 1mcg/kg/dose (with a dosing interval of 3 or 4 hours), increases by 25% of initial dose every 12-24 hrs. Decrease by 10% of max dose every 24 hrs.	Morphine n=10 Participants Babies randomized to morphine will receive 0.06 mg/kg/dose (with a dosing interval of 3 or 4 hours). Morphine: Starting dose is 0.06 mg/kg/dose (every 3 or 4 hours), increases by 25% of initial dose every 12-24 hrs. Decrease by 10% of max dose every 24 hrs.
Ages and Stages Questionnaire Third Edition (ASQ-3) Communication · Above cutoffs	6 Participants	7 Participants
Ages and Stages Questionnaire Third Edition (ASQ-3) Communication · Close to cutoffs	0 Participants	3 Participants
Ages and Stages Questionnaire Third Edition (ASQ-3) Communication · Below cutoffs	1 Participants	0 Participants
Ages and Stages Questionnaire Third Edition (ASQ-3) Gross motor · Above cutoffs	7 Participants	10 Participants
Ages and Stages Questionnaire Third Edition (ASQ-3) Gross motor · Close to cutoffs	0 Participants	0 Participants
Ages and Stages Questionnaire Third Edition (ASQ-3) Gross motor · Below cutoffs	0 Participants	0 Participants
Ages and Stages Questionnaire Third Edition (ASQ-3) Fine motor · Above cutoffs	6 Participants	8 Participants
Ages and Stages Questionnaire Third Edition (ASQ-3) Fine motor · Close to cutoffs	1 Participants	2 Participants
Ages and Stages Questionnaire Third Edition (ASQ-3) Fine motor · Below cutoffs	0 Participants	0 Participants
Ages and Stages Questionnaire Third Edition (ASQ-3) Problem solving · Above cutoffs	4 Participants	9 Participants
Ages and Stages Questionnaire Third Edition (ASQ-3) Problem solving · Close to cutoffs	3 Participants	1 Participants
Ages and Stages Questionnaire Third Edition (ASQ-3) Problem solving · Below cutoffs	0 Participants	0 Participants
Ages and Stages Questionnaire Third Edition (ASQ-3) Personal/social · Above cutoffs	7 Participants	10 Participants
Ages and Stages Questionnaire Third Edition (ASQ-3) Personal/social · Close to cutoffs	0 Participants	0 Participants
Ages and Stages Questionnaire Third Edition (ASQ-3) Personal/social · Below cutoffs	0 Participants	0 Participants

PRIMARY outcome

Timeframe: 24 months

Population: The ASQ-3 at 24 months was used for babies who were unable to have the Bayley assessment due to COVID-19 research restrictions. The babies who had the Bayley did not have the ASQ performed.

Outcome measures

Outcome measures
Measure	Clonidine n=14 Participants Babies randomized to clonidine will receive 1mcg/kg/dose (with a dosing interval of 3 or 4 hours). Clonidine: 1mcg/kg/dose (with a dosing interval of 3 or 4 hours), increases by 25% of initial dose every 12-24 hrs. Decrease by 10% of max dose every 24 hrs.	Morphine n=11 Participants Babies randomized to morphine will receive 0.06 mg/kg/dose (with a dosing interval of 3 or 4 hours). Morphine: Starting dose is 0.06 mg/kg/dose (every 3 or 4 hours), increases by 25% of initial dose every 12-24 hrs. Decrease by 10% of max dose every 24 hrs.
Ages and Stages Questionnaire Third Edition (ASQ-3) Communication · Above cutoffs	8 Participants	8 Participants
Ages and Stages Questionnaire Third Edition (ASQ-3) Communication · Close to cutoffs	2 Participants	2 Participants
Ages and Stages Questionnaire Third Edition (ASQ-3) Communication · Below cutoffs	4 Participants	1 Participants
Ages and Stages Questionnaire Third Edition (ASQ-3) Gross motor · Above cutoffs	13 Participants	10 Participants
Ages and Stages Questionnaire Third Edition (ASQ-3) Gross motor · Close to cutoffs	1 Participants	1 Participants
Ages and Stages Questionnaire Third Edition (ASQ-3) Gross motor · Below cutoffs	0 Participants	0 Participants
Ages and Stages Questionnaire Third Edition (ASQ-3) Fine motor · Above cutoffs	8 Participants	8 Participants
Ages and Stages Questionnaire Third Edition (ASQ-3) Fine motor · Close to cutoffs	4 Participants	3 Participants
Ages and Stages Questionnaire Third Edition (ASQ-3) Fine motor · Below cutoffs	2 Participants	0 Participants
Ages and Stages Questionnaire Third Edition (ASQ-3) Problem solving · Above cutoffs	12 Participants	9 Participants
Ages and Stages Questionnaire Third Edition (ASQ-3) Problem solving · Close to cutoffs	2 Participants	2 Participants
Ages and Stages Questionnaire Third Edition (ASQ-3) Problem solving · Below cutoffs	0 Participants	0 Participants
Ages and Stages Questionnaire Third Edition (ASQ-3) Personal/social · Above cutoffs	12 Participants	10 Participants
Ages and Stages Questionnaire Third Edition (ASQ-3) Personal/social · Close to cutoffs	1 Participants	1 Participants
Ages and Stages Questionnaire Third Edition (ASQ-3) Personal/social · Below cutoffs	1 Participants	0 Participants

PRIMARY outcome

Timeframe: Once post discharge (between 18 months up to 24 months of age)

Population: Only children in the treated cohorts had the CBCL. Participants who were considered lost to follow up did not have the CBCL.

The CBCL/1.5-5 is validated for children ages 1.5 to 5 years old. It obtains caregivers' ratings of 113 behavior items. Scores are broken down into internalizing problems (scores range 29-100, normal is below 60), externalizing problems (scores range from 28-100, normal is below 60), and total problems (range is 28-100, normal is below 60). Items are scored on the following syndrome scales: Emotionally Reactive, Anxious/Depressed, Somatic Complaints, Withdrawn, Attention Problems, Aggressive Behavior, and Sleep Problems. Items are also scored on the following DSM-oriented scales: Affective Problems, Anxiety Problems, Pervasive Developmental Problems, Attention Deficit/Hyperactivity Problems, Stress Problems, Autism Spectrum Problems, and Oppositional Defiant Problems. The CBCL consists of 113 items, scored on a three-point Likert scale (0=absent, 1= occurs sometimes, 2=occurs often)

Outcome measures

Outcome measures
Measure	Clonidine n=15 Participants Babies randomized to clonidine will receive 1mcg/kg/dose (with a dosing interval of 3 or 4 hours). Clonidine: 1mcg/kg/dose (with a dosing interval of 3 or 4 hours), increases by 25% of initial dose every 12-24 hrs. Decrease by 10% of max dose every 24 hrs.	Morphine n=24 Participants Babies randomized to morphine will receive 0.06 mg/kg/dose (with a dosing interval of 3 or 4 hours). Morphine: Starting dose is 0.06 mg/kg/dose (every 3 or 4 hours), increases by 25% of initial dose every 12-24 hrs. Decrease by 10% of max dose every 24 hrs.
Childhood Behavior Checklist (CBCL) T-Scores Internalizing Problems	52.31 score on a scale Standard Deviation 10.4	50.9 score on a scale Standard Deviation 13.9
Childhood Behavior Checklist (CBCL) T-Scores Externalizing Problems	54.8 score on a scale Standard Deviation 13.4	53.5 score on a scale Standard Deviation 17.0
Childhood Behavior Checklist (CBCL) T-Scores Total Problems	53.6 score on a scale Standard Deviation 12.6	53.5 score on a scale Standard Deviation 13.5

SECONDARY outcome

Timeframe: 60 days

Total number days of treatment

Outcome measures

Outcome measures
Measure	Clonidine n=60 Participants Babies randomized to clonidine will receive 1mcg/kg/dose (with a dosing interval of 3 or 4 hours). Clonidine: 1mcg/kg/dose (with a dosing interval of 3 or 4 hours), increases by 25% of initial dose every 12-24 hrs. Decrease by 10% of max dose every 24 hrs.	Morphine n=60 Participants Babies randomized to morphine will receive 0.06 mg/kg/dose (with a dosing interval of 3 or 4 hours). Morphine: Starting dose is 0.06 mg/kg/dose (every 3 or 4 hours), increases by 25% of initial dose every 12-24 hrs. Decrease by 10% of max dose every 24 hrs.
Duration of Treatment	17 days Interval 15.0 to 19.0	15 days Interval 13.0 to 17.0

SECONDARY outcome

Timeframe: Once post discharge (between 18 months up to 24 months of age)

Population: Participants who were lost to follow up did not have the CBCL.

On the CBCL 1.5-5, T-scores, with a mean of 50 and a standard deviation of 10, are used to interpret results, with scores of 65 or higher indicating a clinical range, and scores between 60 and 64 suggesting a borderline clinical range.

Outcome measures

Outcome measures
Measure	Clonidine n=15 Participants Babies randomized to clonidine will receive 1mcg/kg/dose (with a dosing interval of 3 or 4 hours). Clonidine: 1mcg/kg/dose (with a dosing interval of 3 or 4 hours), increases by 25% of initial dose every 12-24 hrs. Decrease by 10% of max dose every 24 hrs.	Morphine n=24 Participants Babies randomized to morphine will receive 0.06 mg/kg/dose (with a dosing interval of 3 or 4 hours). Morphine: Starting dose is 0.06 mg/kg/dose (every 3 or 4 hours), increases by 25% of initial dose every 12-24 hrs. Decrease by 10% of max dose every 24 hrs.
Childhood Behavior Checklist 1.5-5 T-Scores Internalizing Problems Borderline T-Scores	5 Participants	2 Participants
Childhood Behavior Checklist 1.5-5 T-Scores Internalizing Problems Clinical Range T-Scores	1 Participants	8 Participants
Childhood Behavior Checklist 1.5-5 T-Scores Externalizing Problems Borderline T-Scores	2 Participants	2 Participants
Childhood Behavior Checklist 1.5-5 T-Scores Externalizing Problems Clinical Range T-Scores	3 Participants	6 Participants
Childhood Behavior Checklist 1.5-5 T-Scores Total Problems Borderline T-Scores	3 Participants	2 Participants
Childhood Behavior Checklist 1.5-5 T-Scores Total Problems Clinical Range T-Scores	1 Participants	8 Participants

Adverse Events

Clonidine

Serious events: 9 serious events

Other events: 52 other events

Deaths: 1 deaths

Morphine

Serious events: 15 serious events

Other events: 24 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Other adverse events
Measure	Clonidine n=60 participants at risk Babies randomized to clonidine will receive 1mcg/kg/dose (with a dosing interval of 3 or 4 hours). Clonidine: 1mcg/kg/dose (with a dosing interval of 3 or 4 hours), increases by 25% of initial dose every 12-24 hrs. Decrease by 10% of max dose every 24 hrs.	Morphine n=60 participants at risk Babies randomized to morphine will receive 0.06 mg/kg/dose (with a dosing interval of 3 or 4 hours). Morphine: Starting dose is 0.06 mg/kg/dose (every 3 or 4 hours), increases by 25% of initial dose every 12-24 hrs. Decrease by 10% of max dose every 24 hrs.
Nervous system disorders Finnegan scores consecutively >8	40.0% 24/60 • Adverse events were collected from the time of consent until the subject was off study. For subjects who completed the entire study, the maximum amount of time for AE collection is 26 months from date of consent. AEs were collected through the health system EMR and patient reports.	28.3% 17/60 • Adverse events were collected from the time of consent until the subject was off study. For subjects who completed the entire study, the maximum amount of time for AE collection is 26 months from date of consent. AEs were collected through the health system EMR and patient reports.
Investigations Adjunct medication added	21.7% 13/60 • Adverse events were collected from the time of consent until the subject was off study. For subjects who completed the entire study, the maximum amount of time for AE collection is 26 months from date of consent. AEs were collected through the health system EMR and patient reports.	3.3% 2/60 • Adverse events were collected from the time of consent until the subject was off study. For subjects who completed the entire study, the maximum amount of time for AE collection is 26 months from date of consent. AEs were collected through the health system EMR and patient reports.
Investigations Phenobarbitol added	25.0% 15/60 • Adverse events were collected from the time of consent until the subject was off study. For subjects who completed the entire study, the maximum amount of time for AE collection is 26 months from date of consent. AEs were collected through the health system EMR and patient reports.	8.3% 5/60 • Adverse events were collected from the time of consent until the subject was off study. For subjects who completed the entire study, the maximum amount of time for AE collection is 26 months from date of consent. AEs were collected through the health system EMR and patient reports.

Additional Information

Dr. Henrietta Bada

University of Kentucky

Phone: 8593231019

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Measure	Clonidine n=60 participants at risk Babies randomized to clonidine will receive 1mcg/kg/dose (with a dosing interval of 3 or 4 hours). Clonidine: 1mcg/kg/dose (with a dosing interval of 3 or 4 hours), increases by 25% of initial dose every 12-24 hrs. Decrease by 10% of max dose every 24 hrs.	Morphine n=60 participants at risk Babies randomized to morphine will receive 0.06 mg/kg/dose (with a dosing interval of 3 or 4 hours). Morphine: Starting dose is 0.06 mg/kg/dose (every 3 or 4 hours), increases by 25% of initial dose every 12-24 hrs. Decrease by 10% of max dose every 24 hrs.
Cardiac disorders Sustained tachycardia	5.0% 3/60 • Adverse events were collected from the time of consent until the subject was off study. For subjects who completed the entire study, the maximum amount of time for AE collection is 26 months from date of consent. AEs were collected through the health system EMR and patient reports.	6.7% 4/60 • Adverse events were collected from the time of consent until the subject was off study. For subjects who completed the entire study, the maximum amount of time for AE collection is 26 months from date of consent. AEs were collected through the health system EMR and patient reports.
Skin and subcutaneous tissue disorders Skin lesions	3.3% 2/60 • Adverse events were collected from the time of consent until the subject was off study. For subjects who completed the entire study, the maximum amount of time for AE collection is 26 months from date of consent. AEs were collected through the health system EMR and patient reports.	1.7% 1/60 • Adverse events were collected from the time of consent until the subject was off study. For subjects who completed the entire study, the maximum amount of time for AE collection is 26 months from date of consent. AEs were collected through the health system EMR and patient reports.
General disorders Hyperthermia	0.00% 0/60 • Adverse events were collected from the time of consent until the subject was off study. For subjects who completed the entire study, the maximum amount of time for AE collection is 26 months from date of consent. AEs were collected through the health system EMR and patient reports.	1.7% 1/60 • Adverse events were collected from the time of consent until the subject was off study. For subjects who completed the entire study, the maximum amount of time for AE collection is 26 months from date of consent. AEs were collected through the health system EMR and patient reports.
Reproductive system and breast disorders Respiratory Distress	1.7% 1/60 • Adverse events were collected from the time of consent until the subject was off study. For subjects who completed the entire study, the maximum amount of time for AE collection is 26 months from date of consent. AEs were collected through the health system EMR and patient reports.	1.7% 1/60 • Adverse events were collected from the time of consent until the subject was off study. For subjects who completed the entire study, the maximum amount of time for AE collection is 26 months from date of consent. AEs were collected through the health system EMR and patient reports.
Cardiac disorders Increased Heart Rate	1.7% 1/60 • Adverse events were collected from the time of consent until the subject was off study. For subjects who completed the entire study, the maximum amount of time for AE collection is 26 months from date of consent. AEs were collected through the health system EMR and patient reports.	0.00% 0/60 • Adverse events were collected from the time of consent until the subject was off study. For subjects who completed the entire study, the maximum amount of time for AE collection is 26 months from date of consent. AEs were collected through the health system EMR and patient reports.
Gastrointestinal disorders Hematochezia	3.3% 2/60 • Adverse events were collected from the time of consent until the subject was off study. For subjects who completed the entire study, the maximum amount of time for AE collection is 26 months from date of consent. AEs were collected through the health system EMR and patient reports.	3.3% 2/60 • Adverse events were collected from the time of consent until the subject was off study. For subjects who completed the entire study, the maximum amount of time for AE collection is 26 months from date of consent. AEs were collected through the health system EMR and patient reports.
Cardiac disorders Bradycardia	6.7% 4/60 • Adverse events were collected from the time of consent until the subject was off study. For subjects who completed the entire study, the maximum amount of time for AE collection is 26 months from date of consent. AEs were collected through the health system EMR and patient reports.	1.7% 1/60 • Adverse events were collected from the time of consent until the subject was off study. For subjects who completed the entire study, the maximum amount of time for AE collection is 26 months from date of consent. AEs were collected through the health system EMR and patient reports.
Nervous system disorders Seizure	0.00% 0/60 • Adverse events were collected from the time of consent until the subject was off study. For subjects who completed the entire study, the maximum amount of time for AE collection is 26 months from date of consent. AEs were collected through the health system EMR and patient reports.	3.3% 2/60 • Adverse events were collected from the time of consent until the subject was off study. For subjects who completed the entire study, the maximum amount of time for AE collection is 26 months from date of consent. AEs were collected through the health system EMR and patient reports.
Infections and infestations Respiratory Syncytial Virus	0.00% 0/60 • Adverse events were collected from the time of consent until the subject was off study. For subjects who completed the entire study, the maximum amount of time for AE collection is 26 months from date of consent. AEs were collected through the health system EMR and patient reports.	3.3% 2/60 • Adverse events were collected from the time of consent until the subject was off study. For subjects who completed the entire study, the maximum amount of time for AE collection is 26 months from date of consent. AEs were collected through the health system EMR and patient reports.
General disorders Hypothermia	1.7% 1/60 • Adverse events were collected from the time of consent until the subject was off study. For subjects who completed the entire study, the maximum amount of time for AE collection is 26 months from date of consent. AEs were collected through the health system EMR and patient reports.	1.7% 1/60 • Adverse events were collected from the time of consent until the subject was off study. For subjects who completed the entire study, the maximum amount of time for AE collection is 26 months from date of consent. AEs were collected through the health system EMR and patient reports.
Gastrointestinal disorders Dehydration	1.7% 1/60 • Adverse events were collected from the time of consent until the subject was off study. For subjects who completed the entire study, the maximum amount of time for AE collection is 26 months from date of consent. AEs were collected through the health system EMR and patient reports.	0.00% 0/60 • Adverse events were collected from the time of consent until the subject was off study. For subjects who completed the entire study, the maximum amount of time for AE collection is 26 months from date of consent. AEs were collected through the health system EMR and patient reports.
General disorders Poor feeding	0.00% 0/60 • Adverse events were collected from the time of consent until the subject was off study. For subjects who completed the entire study, the maximum amount of time for AE collection is 26 months from date of consent. AEs were collected through the health system EMR and patient reports.	3.3% 2/60 • Adverse events were collected from the time of consent until the subject was off study. For subjects who completed the entire study, the maximum amount of time for AE collection is 26 months from date of consent. AEs were collected through the health system EMR and patient reports.
Gastrointestinal disorders Pyloric stenosis	0.00% 0/60 • Adverse events were collected from the time of consent until the subject was off study. For subjects who completed the entire study, the maximum amount of time for AE collection is 26 months from date of consent. AEs were collected through the health system EMR and patient reports.	3.3% 2/60 • Adverse events were collected from the time of consent until the subject was off study. For subjects who completed the entire study, the maximum amount of time for AE collection is 26 months from date of consent. AEs were collected through the health system EMR and patient reports.
Renal and urinary disorders Undescended testicle	0.00% 0/60 • Adverse events were collected from the time of consent until the subject was off study. For subjects who completed the entire study, the maximum amount of time for AE collection is 26 months from date of consent. AEs were collected through the health system EMR and patient reports.	1.7% 1/60 • Adverse events were collected from the time of consent until the subject was off study. For subjects who completed the entire study, the maximum amount of time for AE collection is 26 months from date of consent. AEs were collected through the health system EMR and patient reports.
Ear and labyrinth disorders Persistent ear infections	0.00% 0/60 • Adverse events were collected from the time of consent until the subject was off study. For subjects who completed the entire study, the maximum amount of time for AE collection is 26 months from date of consent. AEs were collected through the health system EMR and patient reports.	3.3% 2/60 • Adverse events were collected from the time of consent until the subject was off study. For subjects who completed the entire study, the maximum amount of time for AE collection is 26 months from date of consent. AEs were collected through the health system EMR and patient reports.
Respiratory, thoracic and mediastinal disorders Hypoxia	1.7% 1/60 • Adverse events were collected from the time of consent until the subject was off study. For subjects who completed the entire study, the maximum amount of time for AE collection is 26 months from date of consent. AEs were collected through the health system EMR and patient reports.	0.00% 0/60 • Adverse events were collected from the time of consent until the subject was off study. For subjects who completed the entire study, the maximum amount of time for AE collection is 26 months from date of consent. AEs were collected through the health system EMR and patient reports.