- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03396588
Non-Opiate Treatment After Prenatal Opiate Exposure to Prevent Postnatal Injury to the Young Brain (No-POPPY)
Study Overview
Status
Conditions
Intervention / Treatment
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.
Study Type
Enrollment (Actual)
Phase
- Phase 3
Contacts and Locations
Study Locations
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Kentucky
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Lexington, Kentucky, United States, 40536
- Kentucky Children's Hospital
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Description
Inclusion Criteria:
- 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
Exclusion Criteria:
- Seizures
- Major congenital malformations
- Blood pressure instability
- Major medical condition in addition to NAS
- Parents unable to understand English
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Quadruple
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Active Comparator: Clonidine
Babies randomized to clonidine will receive 1mcg/kg/dose (with a dosing interval of 3 or 4 hours).
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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.
Other Names:
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Active Comparator: Morphine
Babies randomized to morphine will receive 0.06 mg/kg/dose (with a dosing interval of 3 or 4 hours).
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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.
Other Names:
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Neurobehavioral Performance Summary Scores from the Neonatal Intensive Care Unit Network Neurobehavioral Scale (NNNS)
Time Frame: 5-10 days post natal age
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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.
Reference: Lester BM et al.
Summary Statistics of Neonatal Intensive Care Unit Network Neurobehavioral Scale Scores From the Maternal Lifestyle Study: A Quasinormative Sample, in Pediatrics 2004; 113,668.
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5-10 days post natal age
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Neurobehavioral Performance Summary Scores from the Neonatal Intensive Care Unit Network Neurobehavioral Scale (NNNS)
Time Frame: At one month post-natal age (between 4-6 weeks of age), or at discharge, whichever comes first
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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.
Reference: Lester BM et al.
Summary Statistics of Neonatal Intensive Care Unit Network Neurobehavioral Scale Scores From the Maternal Lifestyle Study: A Quasinormative Sample, in Pediatrics 2004; 113,668.
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At one month post-natal age (between 4-6 weeks of age), or at discharge, whichever comes first
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Bayley Scales of Infant and Toddler Development Third Edition
Time Frame: 6 months of life
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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.
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 full-scale score.
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6 months of life
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Bayley Scales of Infant and Toddler Development Third Edition
Time Frame: 1 year of life
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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.
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 full-scale score.
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1 year of life
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Bayley Scales of Infant and Toddler Development Third Edition
Time Frame: 2 years of life
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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.
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 full-scale score.
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2 years of life
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Duration of treatment
Time Frame: 60 days
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Total number days of treatment
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60 days
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Collaborators and Investigators
Sponsor
Collaborators
Investigators
- Principal Investigator: Henrietta S Bada, MD MPH, University of Kentucky
Publications and helpful links
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Estimated)
Study Completion (Estimated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
- Narcotics
- Morphine
- Infant, Newborn, Diseases
- Physiological Effects of Drugs
- Chemically-Induced Disorders
- Mental Disorders
- Peripheral Nervous System Agents
- Substance-Related Disorders
- Clonidine
- Antihypertensive Agents
- Analgesics
- Autonomic Agents
- Sympatholytics
- Neurotransmitter Agents
- Molecular Mechanisms of Pharmacological Action
- Central Nervous System Depressants
- Neonatal Abstinence Syndrome
- Adrenergic alpha-Agonists
- Adrenergic alpha-2 Receptor Agonists
- Opiate use during pregnancy
- Prenatal opiate
- Opiate Alkaloids
Additional Relevant MeSH Terms
- Mental Disorders
- Chemically-Induced Disorders
- Substance-Related Disorders
- Infant, Newborn, Diseases
- Neonatal Abstinence Syndrome
- Physiological Effects of Drugs
- Adrenergic Agents
- Neurotransmitter Agents
- Molecular Mechanisms of Pharmacological Action
- Antihypertensive Agents
- Central Nervous System Depressants
- Autonomic Agents
- Peripheral Nervous System Agents
- Analgesics
- Sensory System Agents
- Adrenergic alpha-2 Receptor Agonists
- Adrenergic alpha-Agonists
- Adrenergic Agonists
- Analgesics, Opioid
- Narcotics
- Sympatholytics
- Morphine
- Clonidine
Other Study ID Numbers
- 11-0534-F34
- 1R01DA043519-01 (U.S. NIH Grant/Contract)
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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