Clonidine Versus Phenobarbital as Adjunctive Therapy for Neonatal Abstinence Syndrome

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).

Study Overview

• Status: Completed
• Conditions: Neonatal Abstinence Syndrome
• Intervention / Treatment: Drug: Phenobarbital; Drug: Clonidine

• Study Type: Interventional
• Enrollment (Actual): 25
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Tennessee
    • Knoxville, Tennessee, United States, 37920
      • University of Tennessee Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 8 months and older (ADULT, OLDER_ADULT, CHILD)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
ACTIVE_COMPARATOR: Phenobarbital; 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; 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.
ACTIVE_COMPARATOR: Clonidine; 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; 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.

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: University of Tennessee Medical Center
• Investigators: Principal Investigator: Carrie Brusseau, PharmD, University of Tennessee Medical Center

Study record dates

Study Major Dates

• Study Start (ACTUAL): October 1, 2018
• Primary Completion (ACTUAL): May 31, 2020
• Study Completion (ACTUAL): May 31, 2020

Study Registration Dates

• First Submitted: September 5, 2018
• First Submitted That Met QC Criteria: September 12, 2018
• First Posted (ACTUAL): September 13, 2018

Study Record Updates

• Last Update Posted (ACTUAL): November 10, 2021
• Last Update Submitted That Met QC Criteria: November 9, 2021
• Last Verified: November 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Chemically-Induced Disorders; Pathologic Processes; Substance-Related Disorders; Disease; Infant, Newborn, Diseases; Syndrome; Neonatal Abstinence Syndrome; Physiological Effects of Drugs; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Antihypertensive Agents; Central Nervous System Depressants; Autonomic Agents; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Excitatory Amino Acid Antagonists; Excitatory Amino Acid Agents; Adrenergic alpha-2 Receptor Agonists; Adrenergic alpha-Agonists; Adrenergic Agonists; Hypnotics and Sedatives; GABA Modulators; GABA Agents; Anticonvulsants; Cytochrome P-450 Enzyme Inducers; Cytochrome P-450 CYP3A Inducers; Cytochrome P-450 CYP2B6 Inducers; Sympatholytics; Clonidine; Phenobarbital
• Other Study ID Numbers: UHS-OB-0001

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No