Comparison of Buprenorphine to Morphine in Treatment of Neonatal Abstinence Syndrome (NAS)

Study Overview
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Brief Summary
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The purpose of the study is to determine whether buprenorphine is a beneficial, safe, cost effective treatment alternative to morphine sulfate in the treatment of Neonatal Abstinence Syndrome (NAS).

Detailed Description
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Neonatal abstinence syndrome is a condition that affects newborns who are exposed to chronic opioid drugs while they are in a mother's uterus (womb) prior to birth. The current standard of care treatment includes morphine sulfate. Buprenorphine is a drug used in adults to treat narcotic dependence and withdrawal, but has not yet been approved for use in newborns as a treatment alternative for Neonatal Abstinence Syndrome. This investigation is designed to measure if sublingual (under the tongue) buprenorphine is able to reduce hospital length of stay and decrease number of days of drug treatment currently required in treatment of NAS. Another goal will be to understand buprenorphine as a cost effective treatment for NAS.

Official Title
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A Randomized Comparison of Sublingual Buprenorphine to Morphine Sulfate in the Treatment of Neonatal Abstinence Syndrome (NAS)

Conditions
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Neonatal Abstinence Syndrome, Neonatal Withdrawal Syndrome

Intervention / Treatment
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* Drug: Buprenorphine
* Drug: Morphine Sulfate


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Infants of corrected gestational age ≥37 weeks Chronic opioid exposure in utero Signs and symptoms of NAS requiring treatment 2 consecutive Finnegan scores ≥8 or any single score ≥12 Exclusion Criteria: Concomitant maternal benzodiazepine or alcohol use 30 days prior to enrollment Life-threatening congenital malformations Intrauterine growth retardation Seizure activity or congenital neurologic abnormalities Concomitant neonatal use of Cytochrome P450 inhibitor or inducers prior to treatment Inability of mother's consent due to altered mental status or comorbid psychiatric disorder Neonatal administration of morphine prior to enrollment into study

Ages Eligible for Study
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Maximum Age: 1 Year

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: Oral morphine sulfate<br>Oral morphine sulfate 0.4 mg/kg/day morphine every 3-4 hours as needed for Finnegan scores suggestive of Neonatal Abstinence Syndrome Other Name: morphine | Drug: Morphine Sulfate<br>* Oral Morphine Sulfate Dosage: Morphine Sulfate Oral Solution 100mg/5mL Initially dosed at 0.4mg/kg per day in six daily doses Duration of medication administration dependent upon infant symptoms of neonatal withdrawal, with mean duration of use at Banner Good Samaritan Hospital currently averaging 25 days.<br>* Other names: NDC: 0406-8003-24;|
| Experimental: Buprenorphine<br>Sublingual Buprenorphine 15.9 µg/kg per day in 3 divided doses, titrated up or escalated down based upon standardized scoring for neonatal abstinence syndrome | Drug: Buprenorphine<br>* The injectable formulation of buprenorphine (Buprenex; Reckitt Benckiser) will be prepared to a final concentration of 0.075 mg/mL in 100% ethanol and simple syrup USP to create a sublingual preparation. Infants initial dose: 15.9 µg/kg per day in 3 divided doses with escalation/weaning based upon standardized scoring of NAS symptoms, using standardized Finnegan scoring Maximum dosage: 60 µg/kg per day Duration: Infants will receive buprenorphine until they are successfully weaned off of opioids and no longer show withdrawal symptoms, evidenced by low Finnegan scores. Mean use in other investigations was 24 days.<br>* Other names: Product Code: 12496-0757;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Hospital length of stay | Number of days of hospital admission | Up to hospital discharge, an anticipated average of 4 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of adverse or serious adverse events |  | Up to hospital discharge, with length of stay currently averaging approximately 4 weeks | 
| Cost efficiency of buprenorphine | Cost of buprenorphine as a product of number of days of administration | At least 48 prior to hospital discharge, with anticipated discharge averaging to be 4 weeks | 
| Withdrawal symptoms | Finnegan methodology to score withdrawal symptoms every four hours of medication administration | Up to hospital discharge, usually occuring on average 4 weeks | 
| Rescue dosage administration | Number of rescue doses of additional medication | Up to hospital discharge, anticipating an average of 4 weeks |