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

Study Description

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Brief Summary:

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).

Condition or disease	Intervention/treatment	Phase
Neonatal Abstinence Syndrome; Neonatal Withdrawal Syndrome	Drug: Buprenorphine; Drug: Morphine Sulfate	Phase 2

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 Design

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Study Type :	Interventional (Clinical Trial)
Estimated Enrollment :	64 participants
Allocation:	Randomized
Intervention Model:	Parallel Assignment
Masking:	Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose:	Treatment
Official Title:	A Randomized Comparison of Sublingual Buprenorphine to Morphine Sulfate in the Treatment of Neonatal Abstinence Syndrome (NAS)
Study Start Date :	December 2012
Actual Primary Completion Date :	November 2017
Estimated Study Completion Date :	April 2018

Arms and Interventions

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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: Oral Morphine Sulfate; Morphine; 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

Outcome Measures

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Primary Outcome Measures :

1. Hospital length of stay [ Time Frame: Up to hospital discharge, an anticipated average of 4 weeks ]
   Number of days of hospital admission

Secondary Outcome Measures :

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

Eligibility Criteria

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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Ages Eligible for Study:	up to 1 Year (Child)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

Criteria

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

Contacts and Locations

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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Locations

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

Sponsors and Collaborators

Mednax Center for Research, Education, Quality and Safety

Investigators

Principal Investigator:	Gregory Martin, MD	Banner - University Medical Center Phoenix

More Information

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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Responsible Party:	Mednax Center for Research, Education, Quality and Safety
ClinicalTrials.gov Identifier:	NCT01708707 History of Changes
Other Study ID Numbers:	Banner IRB 01-13-0030
First Posted:	October 17, 2012
Last Update Posted:	March 29, 2018
Last Verified:	March 2018

Additional relevant MeSH terms:

Syndrome; Substance Withdrawal Syndrome; Neonatal Abstinence Syndrome; Disease; Pathologic Processes; Substance-Related Disorders; Chemically-Induced Disorders; Mental Disorders; Infant, Newborn, Diseases; Morphine	Buprenorphine; Analgesics, Opioid; Narcotics; Central Nervous System Depressants; Physiological Effects of Drugs; Analgesics; Sensory System Agents; Peripheral Nervous System Agents; Narcotic Antagonists