Comparison of Buprenorphine to Morphine in Treatment of Neonatal Abstinence Syndrome (NAS)

A Randomized Comparison of Sublingual Buprenorphine to Morphine Sulfate in the Treatment of Neonatal Abstinence Syndrome (NAS)

The purpose of the study is to determine whether buprenorphine is a beneficial, safe, cost effective treatment alternative to morphine sulfate in the treatment of Neonatal Abstinence Syndrome (NAS).

Study Overview

• Status: Completed
• Conditions: Neonatal Abstinence Syndrome; Neonatal Withdrawal Syndrome
• Intervention / Treatment: Drug: Morphine Sulfate; Drug: Buprenorphine

Detailed Description

Neonatal abstinence syndrome is a condition that affects newborns who are exposed to chronic opioid drugs while they are in a mother's uterus (womb) prior to birth. The current standard of care treatment includes morphine sulfate. Buprenorphine is a drug used in adults to treat narcotic dependence and withdrawal, but has not yet been approved for use in newborns as a treatment alternative for Neonatal Abstinence Syndrome. This investigation is designed to measure if sublingual (under the tongue) buprenorphine is able to reduce hospital length of stay and decrease number of days of drug treatment currently required in treatment of NAS. Another goal will be to understand buprenorphine as a cost effective treatment for NAS.

• Study Type: Interventional
• Enrollment (Actual): 29
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Phoenix, Arizona, United States, 85006
      • Banner - University Medical Center Phoenix

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: No older than 1 year (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Infants of corrected gestational age ≥37 weeks
• Chronic opioid exposure in utero
• Signs and symptoms of NAS requiring treatment
• 2 consecutive Finnegan scores ≥8 or any single score ≥12

Exclusion Criteria:

• Concomitant maternal benzodiazepine or alcohol use 30 days prior to enrollment
• Life-threatening congenital malformations
• Intrauterine growth retardation
• Seizure activity or congenital neurologic abnormalities
• Concomitant neonatal use of Cytochrome P450 inhibitor or inducers prior to treatment
• Inability of mother's consent due to altered mental status or comorbid psychiatric disorder
• Neonatal administration of morphine prior to enrollment into study

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Oral morphine sulfate; Oral morphine sulfate 0.4 mg/kg/day morphine every 3-4 hours as needed for Finnegan scores suggestive of Neonatal Abstinence Syndrome Other Name: morphine	Drug: Morphine Sulfate; Oral Morphine Sulfate Dosage: Morphine Sulfate Oral Solution 100mg/5mL Initially dosed at 0.4mg/kg per day in six daily doses Duration of medication administration dependent upon infant symptoms of neonatal withdrawal, with mean duration of use at Banner Good Samaritan Hospital currently averaging 25 days.; Other Names: Morphine; Oral Morphine Sulfate; NDC: 0406-8003-24
Experimental: Buprenorphine; Sublingual Buprenorphine 15.9 µg/kg per day in 3 divided doses, titrated up or escalated down based upon standardized scoring for neonatal abstinence syndrome	Drug: Buprenorphine; The injectable formulation of buprenorphine (Buprenex; Reckitt Benckiser) will be prepared to a final concentration of 0.075 mg/mL in 100% ethanol and simple syrup USP to create a sublingual preparation. Infants initial dose: 15.9 µg/kg per day in 3 divided doses with escalation/weaning based upon standardized scoring of NAS symptoms, using standardized Finnegan scoring Maximum dosage: 60 µg/kg per day Duration: Infants will receive buprenorphine until they are successfully weaned off of opioids and no longer show withdrawal symptoms, evidenced by low Finnegan scores. Mean use in other investigations was 24 days.; Other Names: Sublingual buprenorphine; Other Name: Buprenex (buprenorphine); NDC Number: 12496-0757-1; Product Code: 12496-0757

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Hospital length of stay	Number of days of hospital admission	Up to hospital discharge, an anticipated average of 4 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of adverse or serious adverse events		Up to hospital discharge, with length of stay currently averaging approximately 4 weeks
Cost efficiency of buprenorphine	Cost of buprenorphine as a product of number of days of administration	At least 48 prior to hospital discharge, with anticipated discharge averaging to be 4 weeks
Withdrawal symptoms	Finnegan methodology to score withdrawal symptoms every four hours of medication administration	Up to hospital discharge, usually occuring on average 4 weeks
Rescue dosage administration	Number of rescue doses of additional medication	Up to hospital discharge, anticipating an average of 4 weeks

Collaborators and Investigators

• Sponsor: Pediatrix
• Investigators: Principal Investigator: Gregory Martin, MD, Banner University Medical Center

Publications and helpful links

General Publications

• Zankl A, Martin J, Davey JG, Osborn DA. Opioid treatment for opioid withdrawal in newborn infants. Cochrane Database Syst Rev. 2021 Jul 7;7(7):CD002059. doi: 10.1002/14651858.CD002059.pub4.

Study record dates

Study Major Dates

• Study Start: December 1, 2012
• Primary Completion (Actual): October 1, 2017
• Study Completion (Actual): October 31, 2017

Study Registration Dates

• First Submitted: April 25, 2012
• First Submitted That Met QC Criteria: October 15, 2012
• First Posted (Estimate): October 17, 2012

Study Record Updates

• Last Update Posted (Actual): August 15, 2018
• Last Update Submitted That Met QC Criteria: August 14, 2018
• Last Verified: March 1, 2018

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; Substance Withdrawal Syndrome; Neonatal Abstinence Syndrome; Physiological Effects of Drugs; Central Nervous System Depressants; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Analgesics, Opioid; Narcotics; Narcotic Antagonists; Buprenorphine; Morphine
• Other Study ID Numbers: Banner IRB 01-13-0030