Neonatal Abstinence SyndromePhase 3No-POPPYNCT03396588

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

A Phase 3 study testing Clonidine and Morphine in people with Neonatal Abstinence Syndrome, run by Henrietta Bada at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

Who is it for?: Ages 12 hours to 7 days
Conditions the study is for: Neonatal Abstinence Syndrome
What is being tested?: Clonidine and Morphine
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 120 participants
Where: 1 siteUnited States
Study dates: 7 Dec 2017to 10 Apr 2024
Phase: Phase 3
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 12 hours to 7 days
All sexes
No healthy volunteers
Child

Who may be able to join

Gestational age (GA) > or equal to 35 weeks
Known prenatal opiate exposure (by mother admitting use, mom with positive opiate screen during pregnancy, or positive neonatal urine and meconium screening)
No known prenatal cocaine exposure
No morphine or clonidine dose before enrollment
Symptomatic with Finnegan scores (FS): 3 consecutive scores greater than or equal to 8, OR 2 consecutive scores greater than or equal to 12, and/or with attending decision to treat for NAS
Less than or equal to 7 days of age
Attending physician decides to start pharmacologic treatment and agrees to infant's study participation

Who cannot join

Seizures
Major congenital malformations
Blood pressure instability
Major medical condition in addition to NAS
Parents unable to understand English

Trial locations and contacts

1 site in 1 country.

United States1 site

Kentucky Children's Hospital
Lexington, Kentucky, 40536

Other trials in United States

About this study

The long term goals of our research are to establish the best pharmacological treatment for NAS and determine how pharmacologic treatment of NAS affects long-term developmental outcomes. The objective of this application is to evaluate the effectiveness of clonidine as a treatment for neonates with NAS, in a randomized clinical trial. Our central hypothesis is that clonidine will effectively treat drug withdrawal manifestations in neonates.

Read the detailed description

In this current proposal, the research plan is based on our pilot study, which randomized infants with NAS to receive morphine or clonidine. The treatment groups were similar as to mean birth weight, gestational age, Apgar scores, and postnatal age at treatment. Infants enrolled had no other medical or surgical complications. Treatment was initiated per our NICU standard at the time, and will be continued in this protocol. Total LOS was shorter by about 1 week in the clonidine (mean of 15 days), compared to 21 days in the morphine group.

Aims and Objectives:

To determine whether the treatment of NAS with a non-opiate medication, clonidine, will be more effective than morphine

Compare Clonidine and morphine for the treatment of NAS. Compare the efficacy of each drug which is determined by duration of treatment in number of days, number of dose escalations needed to achieve needed treatment, and the need for second drug treatment.
Evaluate the neurobehavioral performance scores (habituation, orientation, self- regulation, motor/reflexes, and stress/ abstinence scales) using the neonatal intensive care (NICU) network neurobehavioral scale (NNNS) in both treatment groups. This exam will take place after treatment begins, and at one month post-natal age (38-44 weeks post menstrual age) or at discharge, whichever comes first.

To determine whether treatment of NAS with clonidine will result in better early childhood outcomes than those treated with morphine • Compare the cognitive, motor and behavioral development of children in both treatment groups using the Bayley III Scales of Infant Development at 6 months, one and two years of age.

To build population pharmacokinetic/pharmacodynamic models and determine factors that affect exposure and response to morphine and clonidine

Measure blood levels obtained at random times and correlate to Finnegan scores. The pharmacodynamics may help with understanding NAS medications and coping measures in babies.

Conditions: Neonatal Abstinence Syndrome
Being tested: Clonidine, Morphine
Keywords: Opiate use during pregnancy, Clonidine, Morphine, Prenatal opiate, Neonatal Abstinence Syndrome, Infant, Newborn, Diseases, Substance-Related Disorders, Chemically-Induced Disorders, Opiate Alkaloids, Mental Disorders, Narcotics, Central Nervous System Depressants, Physiological Effects of Drugs, Adrenergic alpha-2 Receptor Agonists, Adrenergic alpha-Agonists, Molecular Mechanisms of Pharmacological Action, Antihypertensive Agents, Analgesics, Peripheral Nervous System Agents, Sympatholytics
Medical subject headings: Neonatal Abstinence Syndrome, Infant, Newborn, Diseases, Substance-Related Disorders, Chemically-Induced Disorders, Mental Disorders

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

ClonidineDrug
Also called clonidine hydrochloride
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.
MorphineDrug
Also called Morphine Sulfate
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.

Study groups in NCT03396588
Study group	Role	What they receive
Clonidine	Active comparator	Babies randomized to clonidine will receive 1mcg/kg/dose (with a dosing interval of 3 or 4 hours). Receives: Drug: Clonidine
Morphine	Active comparator	Babies randomized to morphine will receive 0.06 mg/kg/dose (with a dosing interval of 3 or 4 hours). Receives: Drug: Morphine

What is being measured

The primary outcome is the main question the study is designed to answer.

Change in Neurobehavioral Performance Summary Scores From the Neonatal Intensive Care Unit Network Neurobehavioral Scale (NNNS)
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.
Measured: 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.
Bayley Scales of Infant and Toddler Development Third Edition
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.
Measured: 6 months of life
Bayley Scales of Infant and Toddler Development Third Edition
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.
Measured: 1 year of life
Bayley Scales of Infant and Toddler Development Third Edition
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.
Measured: 2 years of life
Ages and Stages Questionnaire Third Edition (ASQ-3)
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).
Measured: 12 months of age
Ages and Stages Questionnaire Third Edition (ASQ-3)
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).
Measured: 24 months
Childhood Behavior Checklist (CBCL) T-Scores
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)
Measured: Once post discharge (between 18 months up to 24 months of age)

Secondary outcomes (2)

Duration of Treatment
Total number days of treatment
Measured: 60 days
Childhood Behavior Checklist 1.5-5 T-Scores
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.
Measured: Once post discharge (between 18 months up to 24 months of age)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

7 Dec 201710 Apr 2024

First posted11 Jan 2018
Study start7 Dec 2017
Primary completion10 Apr 2024
Study completion10 Apr 2024

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (3)Papers the sponsor has linked to this study.
Other trials for Neonatal Abstinence SyndromeStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 3
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Model description: The study is intended to treat NAS using a randomized and double-blind study design to compare the use of opiate (morphine) or non-opiate (clonidine). Newborns meeting the study criteria for drug withdrawal and treatment will be randomized to receive one of the drugs (morphine, clonidine). Newborns requiring a second drug to help relieve the symptoms will be treated with phenobarbital for both groups. Randomization, blinding and dispensing will occur in the Investigational Drug Services Unit. Nursing personnel in the NICU will be masked to the treatment administered to each baby.
Masking: Quadruple blind
Who is masked: Participant, Care provider, Investigator, Outcomes assessor
Enrolment: 120 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT03396588
Sponsor's protocol ID: 11-0534-F34
Other IDs: 1R01DA043519-01
Acronym: No-POPPY
Status last verified: May 2025
First submitted: 13 Dec 2017
Last updated: 23 May 2025
Results posted: Yes, on ClinicalTrials.gov
FDA-regulated drug: Yes
FDA-regulated device: No
Individual data sharing: No

Publications

Bada HS, Sithisarn T, Gibson J, Garlitz K, Caldwell R, Capilouto G, Li Y, Leggas M, Breheny P. Morphine versus clonidine for neonatal abstinence syndrome. Pediatrics. 2015 Feb;135(2):e383-91. doi: 10.1542/peds.2014-2377.
PubMed 25624389
Lester BM, Tronick EZ, LaGasse L, Seifer R, Bauer CR, Shankaran S, Bada HS, Wright LL, Smeriglio VL, Lu J. Summary statistics of neonatal intensive care unit network neurobehavioral scale scores from the maternal lifestyle study: a quasinormative sample. Pediatrics. 2004 Mar;113(3 Pt 2):668-75.
PubMed 14993525
Tang F, Ng CM, Horn J, Bada HS, Leggas M. Pharmacokinetic Modeling and Model-Based Hypothesis Generation for Dose Optimization of Clonidine in Neonates With Neonatal Opioid Withdrawal Syndrome. Clin Pharmacol Ther. 2025 May;117(5):1254-1263. doi: 10.1002/cpt.3507. Epub 2024 Nov 22.
PubMed 39575611

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

Active, not recruiting
Effective Caregiving for Neonatal Abstinence Syndrome: Testing an Instructional Mobile Technology Platform for High-Risk Pregnant Women
Neonatal Abstinence Syndrome, Opioid-use Disorder
Not yet recruiting
Recorded Parent/Caregiver Voice for Infants With Neonatal Opioid Withdrawal Syndrome
Neonatal Opioid Withdrawal Syndrome, Prenatal Opioid Exposure
Recruiting
Effect of Music Therapy on Infants With Neonatal Abstinence Syndrome
NAS
Recruiting
An Intervention Mapping Approach to Closing the Gap in Maternal OUD and Infant NAS Care (SUPPORT)
Opioid Use Disorder, Neonatal Abstinence Syndrome
Active, not recruiting
Neurostimulation to Improve NOWS Outcomes
Neonatal Opioid Withdrawal Syndrome, Neonatal Abstinence Syndrome

All Neonatal Abstinence Syndrome trials

Study at a glance

From the registry record, last updated by the sponsor on 23 May 2025. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Non-Opiate Treatment After Prenatal Opiate Exposure to Prevent Postnatal Injury to the Young Brain
ClinicalTrials.gov ID: NCT03396588
Acronym / sponsor ID: No-POPPY / 11-0534-F34
Conditions: Neonatal Abstinence Syndrome
Keywords: Opiate use during pregnancy, Clonidine, Morphine, Prenatal opiate, Neonatal Abstinence Syndrome, Infant, Newborn, Diseases, Substance-Related Disorders, Chemically-Induced Disorders
Phase: Phase 3
Study type: Interventional
Recruitment status: Completed
Enrolment: 120 participants (actual)
Lead sponsor: Henrietta BadaUniversity, hospital or other
Collaborators: National Institute on Drug Abuse (NIDA)
Study start: 7 Dec 2017 (actual)
Primary completion: 10 Apr 2024 (actual)
Study completion: 10 Apr 2024 (actual)
First posted: 11 Jan 2018 (actual)
Results: Posted 23 May 2025

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

Aims and Objectives:

To determine whether the treatment of NAS with a non-opiate medication, clonidine, will be more effective than morphine

Compare Clonidine and morphine for the treatment of NAS. Compare the efficacy of each drug which is determined by duration of treatment in number of days, number of dose escalations needed to achieve needed treatment, and the need for second drug treatment.
Evaluate the neurobehavioral performance scores (habituation, orientation, self- regulation, motor/reflexes, and stress/ abstinence scales) using the neonatal intensive care (NICU) network neurobehavioral scale (NNNS) in both treatment groups. This exam will take place after treatment begins, and at one month post-natal age (38-44 weeks post menstrual age) or at discharge, whichever comes first.

To build population pharmacokinetic/pharmacodynamic models and determine factors that affect exposure and response to morphine and clonidine

Measure blood levels obtained at random times and correlate to Finnegan scores. The pharmacodynamics may help with understanding NAS medications and coping measures in babies.

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Quadruple blind (participant, care provider, investigator, outcomes assessor)
Number of arms: 2
Model description: The study is intended to treat NAS using a randomized and double-blind study design to compare the use of opiate (morphine) or non-opiate (clonidine). Newborns meeting the study criteria for drug withdrawal and treatment will be randomized to receive one of the drugs (morphine, clonidine). Newborns requiring a second drug to help relieve the symptoms will be treated with phenobarbital for both groups. Randomization, blinding and dispensing will occur in the Investigational Drug Services Unit. Nursing personnel in the NICU will be masked to the treatment administered to each baby.

Arm	Type	Receives
Clonidine	Active comparator	Drug: ClonidineBabies randomized to clonidine will receive 1mcg/kg/dose (with a dosing interval of 3 or 4 hours).
Morphine	Active comparator	Drug: MorphineBabies randomized to morphine will receive 0.06 mg/kg/dose (with a dosing interval of 3 or 4 hours).

Who may qualify

Ages: 12 hours to 7 days
Sex: All
Healthy volunteers: Not accepted
Age groups: Child

Key inclusion criteria (7 listed)

Gestational age (GA) > or equal to 35 weeks
Known prenatal opiate exposure (by mother admitting use, mom with positive opiate screen during pregnancy, or positive neonatal urine and meconium screening)
No known prenatal cocaine exposure
No morphine or clonidine dose before enrollment
Symptomatic with Finnegan scores (FS): 3 consecutive scores greater than or equal to 8, OR 2 consecutive scores greater than or equal to 12, and/or with attending decision to treat for NAS

Key exclusion criteria (5 listed)

Seizures
Major congenital malformations
Blood pressure instability
Major medical condition in addition to NAS
Parents unable to understand English

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
ClonidineAlso: clonidine hydrochloride1mcg/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.	Drug	Clonidine
MorphineAlso: Morphine SulfateStarting 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.	Drug	Morphine

Primary outcome

Change in Neurobehavioral Performance Summary Scores From the Neonatal Intensive Care Unit Network Neurobehavioral Scale (NNNS)
Time frame: 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.
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.
Bayley Scales of Infant and Toddler Development Third Edition
Time frame: 6 months of life
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.
Bayley Scales of Infant and Toddler Development Third Edition
Time frame: 1 year of life
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.
Bayley Scales of Infant and Toddler Development Third Edition
Time frame: 2 years of life
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.
Ages and Stages Questionnaire Third Edition (ASQ-3)
Time frame: 12 months of age
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).
Ages and Stages Questionnaire Third Edition (ASQ-3)
Time frame: 24 months
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).
Childhood Behavior Checklist (CBCL) T-Scores
Time frame: Once post discharge (between 18 months up to 24 months of age)
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)

2 secondary outcomes

Duration of Treatment
Time frame: 60 days
Childhood Behavior Checklist 1.5-5 T-Scores
Time frame: Once post discharge (between 18 months up to 24 months of age)

Results and safety

Results posted to the registry on 23 May 2025, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Clonidine	60	58
Morphine	60	57

Primary outcome: Change in Neurobehavioral Performance Summary Scores From the Neonatal Intensive Care Unit Network Neurobehavioral Scale (NNNS)

Time frame: 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.. Mean (95% Confidence Interval). Unit: score on a scale

Measure	Clonidine n = 54	Morphine n = 51
Habituation	0.5 (-1.0 to 1.0)	0.3 (-1.0 to 1.0)
Attention	1.0 (-0.1 to 2.0)	0.6 (0.2 to 1.6)
Handling	-0.1 (-0.4 to 0.1)	0.1 (0.0 to 0.4)
Quality of movement	0.1 (-0.3 to 0.8)	0.0 (-0.5 to 0.5)
Regulation	0.5 (-0.5 to 1.3)	-0.2 (-0.8 to 0.2)
Non-optimal reflexes	-1.0 (-2.5 to 1.0)	-1.0 (-2.0 to 1.0)
Asymmetry total/reflexes	0.0 (0.0 to 0.0)	0.0 (0.0 to 0.0)
Arousal	-0.1 (-0.6 to 0.3)	0.4 (0.0 to 0.7)

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

Primary outcome: Bayley Scales of Infant and Toddler Development Third Edition

Time frame: 6 months of life. Mean (Standard Deviation). Unit: score on a scale

Measure	Clonidine n = 32	Morphine n = 38
Cognitive	113.0 (12.8)	111.8 (11.1)
Language	91.8 (13.4)	87.7 (13.5)
Motor	102.4 (16.4)	97.4 (12.3)

Population analysed: 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.

Primary outcome: Bayley Scales of Infant and Toddler Development Third Edition

Time frame: 1 year of life. Mean (Standard Deviation). Unit: score on a scale

Measure	Clonidine n = 19	Morphine n = 18
Cognitive	98.2 (11.5)	97.2 (10.8)
Language	91.8 (11.6)	92.2 (12.2)
Motor	99.1 (12.2)	96.2 (9.3)

Population analysed: 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.

Primary outcome: Bayley Scales of Infant and Toddler Development Third Edition

Time frame: 2 years of life. Mean (Standard Deviation). Unit: score on a scale

Measure	Clonidine n = 7	Morphine n = 8
Cognitive	84.3 (6.7)	81.1 (9.6)
Language	95.4 (9.4)	86.2 (11.0)
Motor	97.6 (7.2)	96.0 (9.8)

Population analysed: 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.

2 secondary outcomes are reported in the full results.

Adverse events

Time frame: 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.. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Clonidine	9 of 60 (15%)	52 of 60 (86.7%)	1 of 60
Morphine	15 of 60 (25%)	24 of 60 (40%)	0 of 60

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 23 May 2025.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Background: PubMed 25624389Bada HS, Sithisarn T, Gibson J, Garlitz K, Caldwell R, Capilouto G, Li Y, Leggas M, Breheny P. Morphine versus clonidine for neonatal abstinence syndrome. Pediatrics. 2015 Feb;135(2):e383-91. doi: 10.1542/peds.2014-2377.
Background: PubMed 14993525Lester BM, Tronick EZ, LaGasse L, Seifer R, Bauer CR, Shankaran S, Bada HS, Wright LL, Smeriglio VL, Lu J. Summary statistics of neonatal intensive care unit network neurobehavioral scale scores from the maternal lifestyle study: a quasinormative sample. Pediatrics. 2004 Mar;113(3 Pt 2):668-75.
Derived from this study: PubMed 39575611Tang F, Ng CM, Horn J, Bada HS, Leggas M. Pharmacokinetic Modeling and Model-Based Hypothesis Generation for Dose Optimization of Clonidine in Neonates With Neonatal Opioid Withdrawal Syndrome. Clin Pharmacol Ther. 2025 May;117(5):1254-1263. doi: 10.1002/cpt.3507. Epub 2024 Nov 22.
Individual participant dataSharing planned: No

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Henrietta S Bada, MD MPH principal investigator

University of Kentucky

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Clonidine and Morphine in people with Neonatal Abstinence Syndrome, run by Henrietta Bada at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 7 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 23 May 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 23 May 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Change in Neurobehavioral Performance Summary Scores From the Neonatal Intensive Care Unit Network Neurobehavioral Scale (NNNS) (time frame: 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.). The study lists 7 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03396588, which also lists 3 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 23 May 2025.