Clonidine as Adjunct to Morphine for Neonatal Abstinence Syndrome

Phase 4

Terminated

Brief Summary: 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: 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

Recruitment & Eligibility

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

Arm && Interventions

Group	Intervention	Description
clonidine	Clonidine	Clonidine is started at 6mcg/kg/day and increased to 12 mcg/kg/d for the duration of the study period
Placebo	Placebo	Placebo solution will be given for the duration of the study period

Primary Outcome Measures

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

Secondary Outcome Measures

Name	Time	Method
Total Number of Episodes of Blood Pressure (mm of Hg) Variability	From beginning of morphine therapy during NICU admission until discharge from the hospital, up to 100 days	Number of episodes of hypotension (blood pressure \< 5th percentile for age) and hypertension (blood pressure \> 95th percentile for age)
Average Daily Dose of Oral Morphine Over Hospital Stay	From beginning of morphine therapy during NICU admission until discharge from the hospital, up to 100 days	The average daily dose of morphine used throughout study period in mg/kg/day
Maximum Dose of Morphine Used	From beginning of morphine therapy during NICU admission until discharge from the hospital, up to 100 days	The maximum dose of morphine in mg/kg used for symptom control
Duration of Hospital Stay	From beginning of morphine therapy during NICU admission until discharge from the hospital, up to 100 days	Number of days spent in the hospital
Total Number of Episodes of Heart Rate Variability (Heart Beats/Min)	From beginning of morphine therapy during NICU admission until discharge from the hospital, up to 100 days	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