Clonidine as Adjunct to Morphine for Neonatal Abstinence Syndrome

Study Overview
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Brief Summary
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This is a prospective randomized double blinded study comparing the effect on duration of pharmacologic treatment and duration of hospital stay when using clonidine at 12 µg/kilogram/day as an adjunct to oral morphine as compared to morphine monotherapy in the management of term and near term infants with neonatal abstinence syndrome (NAS)

Detailed Description
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Neonatal abstinence syndrome (NAS) is an emerging epidemic and has lead to a tremendous increase in cost of medical care. Opioids are the mainstay of treatment for NAS although there are concerns about possible short-term and long-term effects including but not limited to adverse neurodevelopmental outcomes. Other drugs such as clonidine, phenobarbitone, methadone and buprenorphine have been evaluated to limit the postnatal exposure to opioids in these infants. Clonidine is an alpha 2 receptor and can lessen withdrawal manifestations. The addition of clonidine at 6 µg/kilogram/day to morphine in the management of NAS has been shown to reduce the duration of pharmacotherapy by about 27% in a previous study. A recent pilot study reported reduction of treatment duration for NAS with clonidine (12 µg/kilogram/day) monotherapy as compared to morphine monotherapy. The study reported no adverse effects in study subjects at the doses used in the study. The investigators hypothesize that there will be a minimum of 30% reduction in the treatment duration with 12 µg/kilogram/day clonidine used as adjuncts to standard morphine treatment as compared to morphine monotherapy in the management of term and near term infants with NAS

Official Title
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Clonidine as Adjunct to Morphine in the Management of Term and Near Term Infants With Neonatal Abstinence Syndrome

Conditions
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Neonatal Abstinence Syndrome

Intervention / Treatment
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* Drug: Clonidine
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Requiring neonatal intensive care unit (NICU) admission for management of neonatal abstinence syndrome Gestational age greater than or equal to 36 weeks Less than or equal to 48 hours of treatment with morphine for NAS Exclusion Criteria: Presence of seizures Congenital malformations, genetic syndromes or the presence of TORCH infections Major medical problems Heart rate and/or blood pressure instability

Ages Eligible for Study
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Minimum Age: 36 Weeks
Maximum Age: 45 Weeks

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: clonidine<br>Clonidine is started at 6mcg/kg/day and increased to 12 mcg/kg/d for the duration of the study period | Drug: Clonidine<br>* clonidine will be given at 12 mcg/kg/d to the experimental arm in addition to oral morphine<br>|
| Placebo Comparator: Placebo<br>Placebo solution will be given for the duration of the study period | Drug: Placebo<br>* Placebo with volume similar to clonidine at 12 mcg/kg/d will be given to this arm in addition to oral morphine<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Duration of Pharmacotherapy for NAS | The length of time in days from the initiation of pharmacotherapy on day 1 until the medication has been stopped | From beginning of morphine therapy during NICU admission until discharge from the hospital, up to 100 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Duration of Hospital Stay | Number of days spent in the hospital | From beginning of morphine therapy during NICU admission until discharge from the hospital, up to 100 days | 
| Maximum Dose of Morphine Used | The maximum dose of morphine in mg/kg used for symptom control | From beginning of morphine therapy during NICU admission until discharge from the hospital, up to 100 days | 
| Average Daily Dose of Oral Morphine Over Hospital Stay | The average daily dose of morphine used throughout study period in mg/kg/day | From beginning of morphine therapy during NICU admission until discharge from the hospital, up to 100 days | 
| Total Number of Episodes of Heart Rate Variability (Heart Beats/Min) | Number of episodes of bradycardia (Heart rate < 60/min for a minimum of 20 seconds and not associated with apnea or signs of reflux such as emesis, regurgitation of milk into the mouth or nose, arching while feeding, number of episodes of tachycardia (Heart rate > 200/min) and not related to pain and/or agitation | From beginning of morphine therapy during NICU admission until discharge from the hospital, up to 100 days | 
| Total Number of Episodes of Blood Pressure (mm of Hg) Variability | Number of episodes of hypotension (blood pressure < 5th percentile for age) and hypertension (blood pressure > 95th percentile for age) | From beginning of morphine therapy during NICU admission until discharge from the hospital, up to 100 days |