NAS Treatment - Opiate Versus Non-Opiate

Study Overview
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Brief Summary
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The purpose of this study is to compare two different medicines to treat babies with opiate withdrawal. The treatment medicines are morphine, which is an opiate, and clonidine, a non-opiate. Morphine is a narcotic medicine, with is included in most pain killers. Clonidine is another drug, but is different from morphine. It is also used for babies, and even adults for withdrawal symptoms. Both drugs are effective, but the purpose of this study is to see if one may be better than the other.

Detailed Description
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Withdrawal from drugs, called Neonatal abstinence syndrome (NAS), is a group of symptoms that occurs to babies whose mother took or used drugs (prescription, addicting, illegal, pain pills, or drugs for addiction treatment) during pregnancy. Medicines the mother takes while pregnant, the baby also takes. Babies may experience withdrawal after delivery, and may need treatment. There are different ways to treat babies with withdrawal - about 50% of doctors use morphine, an opiate, to treat these babies, the rest uses other drugs, like clonidine and phenobarbitol.

Official Title
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Pharmacological Treatment of Neonatal Abstinence Syndrome: Opiate Versus Non-Opiate

Conditions
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Neonatal Abstinence Syndrome

Intervention / Treatment
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* Drug: Morphine
* Drug: Clonidine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Admitted to Neonatal Intensive Care Unit (NICU)- Gestational age (GA) >or= 35 wks Known prenatal opiate exposure (maternal history, positive opiate screen, positive neonatal urine or meconium screen) Symptomatic with Finnegan Neonatal Abstinence Scores meeting NICU protocol for treatment Exclusion Criteria: Seizures Major congenital malformations Unlikely to survive Parents not able to understand English

Ages Eligible for Study
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Minimum Age: 1 Day
Maximum Age: 7 Days

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Morphine<br>Initial dose is 0.4mg/kg/day, divided every 3-4 hours, given PO with feeds. Drug is required until symptoms of withdrawal no longer cause the infant feeding, behavior, or elimination problems, up to 3 months. | Drug: Morphine<br>* Start at 0.4mg/kg/day (divided every 3-4 hours, given with feeds. Dose may be increased 25% of initial dose until symptoms are stable, up to 1 mg/kg/day. Once stable for 72 hrs, weaning may begin (decrease 10% of max dose, every other day). When total dose is <0.1mg/kg/day, may discontinue.<br>* Other names: Morphine sulfate;|
| Active Comparator: Clonidine<br>Dose is started at 5 mcg/kg/day, given PO with feeds, divided every 3-4 hours. Drug is required until symptoms of withdrawal no longer cause the infant feeding, behavior, or elimination problems, up to 3 months. | Drug: Clonidine<br>* Initial dose is 5 mcg/kg/day (divided every 3-4 hrs, given with feeds). Will increase 25% of initial dose every 12-24 hrs until stable, up to 12 mcg/kg/day. Dose is unchanged for 72 hours once stable, then may decrease by 10% every other day. If re-escalation is required, the previous dose may be used with 72 hours for stabilizing.<br>* Other names: clonidine hydrochloride;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Finnegan Neonatal Abstinence Scoring System | Mean of total Finnegan Scores obtained every 3 hours on days 2, 7, and 14 following start of treatment; A score is a number representing the total score or sum from 21 items or symptoms or manifestations of opiate withdrawal in newborn infants. The total score ranges from 0 to 43. Reference: 1. Finnegan LP, Connaughton JF, Jr., Kron RE, et al. Neonatal abstinence syndrome: assessment and management. Addict Dis 1975;2(1-2):141-58. Although normal newborn may manifest mild symptoms that will give scores in the range of 0 to 7. A score of 8 consecutively obtained times 3 indicate that infant will benefit from treatment, in this study morphine or clonidine. A decrease in scores especially to less than 8 is suggestive of a good response to treatment. | 14 days | 
| Duration of Treatment | Total number days of treatment | 120 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. 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. | 5-10 days after treatment starts | 
| 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. 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 | 1 year of life | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Prenatal opiate exposure, neonatal withdrawal, Pharmacologic treatment