Clonidine Versus Phenobarbital as Adjunctive Therapy for Neonatal Abstinence Syndrome

Study Overview
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Brief Summary
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The purpose of this study is to compare clonidine versus phenobarbital as adjunctive therapy in those infants who have failed monotherapy with morphine sulfate for neonatal abstinence syndrome (NAS).

Official Title
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Clonidine Versus Phenobarbital as Adjunctive Therapy for Neonatal Abstinence Syndrome

Conditions
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Neonatal Abstinence Syndrome

Intervention / Treatment
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* Drug: Phenobarbital
* Drug: Clonidine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Infants greater than or equal to 35 weeks gestation age Admitted to the neonatal intensive care unit Failed monotherapy with morphine sulfate therapy Exclusion Criteria: Neonatal abstinence syndrome due to iatrogenic causes Unable to take oral medications at any point during their treatment Infants in the custody of the Department of Child Protective Services with no legal guardian identified at the time of enrollment

Ages Eligible for Study
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Minimum Age: 35 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: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Phenobarbital<br>Phenobarbital loading dose 20mg/kg in 2 divided doses, then 5 mg/kg/day divided every 12 hours. Phenobarbital continued throughout the infants hospitalization. | Drug: Phenobarbital<br>* Phenobarbital loading dose 20 mg/kg in 2 divided doses, then 5 mg/kg/day divided every 12 hours. Phenobarbital dose will be adjusted to obtain desired trough of 25 to 30 mcg/mL. Levels will be obtained on Day 6 then weekly thereafter. Phenobarbital will be tapered over 4 weeks upon discharge from the hospital. The standardized taper is based the patient specific dose at the time of discharge.<br>|
| Active Comparator: Clonidine<br>Clonidine 5 mcg/kg/day divided every 3 hours. Clonidine will be continued to achieve control of NAS symptoms. Clonidine may be weaned after successful discontinuation of oral morphine sulfate. Infants will not be discharged on clonidine. | Drug: Clonidine<br>* Clonidine 5 mcg/kg/day divided every 3 hours. Clonidine will be increased by 1.5 mcg/kg/day to achieve control of NAS symptoms based upon standardized scoring for neonatal abstinence syndrome. Clonidine will be weaned by 25% every 24 hours after successful discontinuation of oral morphine sulfate. Infants will not be discharged on clonidine.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time From Initiation of Adjunctive Therapy Until Hospital Discharge | Number of days from initiation of adjunctive therapy until hospital discharge | From date of randomization until hospital discharge, up to 4 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Length of Stay | Number of days of hospital admission | From date of randomization until hospital discharge, up to 4 months | 
| Length of Oral Morphine Sulfate Therapy | Number of days of oral morphine sulfate therapy | From date of randomization until hospital discharge, up to 4 months | 
| Number of Patients Requiring Triple Therapy | Number of patients requiring a third agent to control withdrawal symptoms | From date of randomization until hospital discharge, up to 4 months | 
| Readmission Rate | Number of patients readmitted to the hospital within 30 days of hospital discharge or discontinuation of phenobarbital. | From date of randomization until 30 days after hospital discharge or discontinuation of phenobarbital, up to 6 months |