Buprenorphine for Treatment of Neonatal Abstinence Syndrome in Infants With In Utero Exposure to Benzodiazepines

Study Overview
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Brief Summary
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The opioid neonatal abstinence syndrome (NAS) is a condition of withdrawal symptoms after utero exposure to opioids. Sublingual buprenorphine shows promise as a new treatment in NAS. This trial will investigate the safety and tolerability of sublingual buprenorphine in infants exposed to both opioids and benzodiazepines in utero or with exposure of opioids in those who are breastfeeding.

Detailed Description
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Infants with in utero exposure to opioids often require therapy with morphine for an extended period. In a clinical trial, sublingual buprenorphine reduced this treatment period by  30%. However, infants with both opioid and benzodiazepine exposure were not included in the trial. This study will test the safety and tolerability of sublingual buprenorphine in infants with in utero exposure to benzodiazepines or who are breastfeeding.

Official Title
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A Randomized, Open Label Clinical Trial of Buprenorphine in the Treatment of Neonatal Abstinence Syndrome in Infants With In Utero Exposure to Benzodiazepines or Are Breastfeeding

Conditions
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Neonatal Abstinence Syndrome

Intervention / Treatment
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* Drug: oral morphine
* Drug: sublingual buprenorphine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: ≥ 37 weeks gestation Exposure to opioids in utero Demonstration of signs and symptoms of neonatal abstinence syndrome requiring treatment Exposure to benzodiazepines in utero and/or receiving breast milk. Benzodiazepine use is defined as maternal use in the past 30 days, and/or receipt of benzodiazepines by prescription (as determined by self-report or intake urine) by the mother 30 days prior to birth. Exclusion Criteria: Major congenital malformations and/or intrauterine growth retardation defined as birth weight <2200 gm Medical illness requiring intensification of medical therapy. This includes, but is not limited to suspected sepsis requiring antibiotic therapy. Hypoglycemia requiring treatment with intravenous dextrose Bilirubin >20 mg/dL (The need for phototherapy is not exclusionary) Seizure activity or other neurologic abnormality
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: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: sublingual buprenorphine<br>Initial daily dose: 15.9 mcg/kg/day; Initial unit dose: 5.3 mcg/kg q8 hours; Maximum daily dose: 60 mcg/kg/day; Up-titration rate: 25%; Weaning rate: 10%; Cessation Dose: Within 10 or 20% of starting dose | Drug: sublingual buprenorphine<br>* Sublingual buprenorphine for the treatment of neonatal abstinence syndrome<br>* Other names: buprenex;|
| Active Comparator: oral morphine<br>Initial daily dose: 0.4 mg/kg/day; Initial unit dose: 0.07 mg/kg q 4 hours; Maximum daily dose: 1.25 mg/kg/day; Up-titration rate: 20%; Weaning rate: 10%; Cessation Dose: 0.025 mg/kg q 4 hours | Drug: oral morphine<br>* Oral morphine for the treatment of neonatal abstinence syndrome<br>* Other names: morphine;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Length of treatment | This endpoint will compare length of treatment (in days) using sublingual buprenorphine or oral morphine solution. | Patients will be followed for the duration of hospital stay, an expected average of 5 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Length of hospitalization | This endpoint will compare length of stay (in days) using sublingual buprenorphine or oral morphine | Patients will be followed for the duration of hospital stay, an expected average of 5 weeks | 
| Number of patients requiring supplemental phenobarbital treatment | This endpoint will compare requirement number of patients who require use of supplemental phenobarbital for treatment of NAS | Patients will be followed for the duration of hospital stay, an expected average of 5 weeks | 
| Number of participants with adverse events as a measure of safety and tolerability | Adverse events will be collected, graded by severity, and assessed for causality referent to study drug. | Patients will be followed for the duration of hospital stay, an expected average of 5 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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morphine, Neonatal Abstinence Syndrome, buprenorphine, benzodiazepine