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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01708707
Recruitment Status : Completed
First Posted : October 17, 2012
Last Update Posted : August 15, 2018
Information provided by (Responsible Party):
Mednax Center for Research, Education, Quality and Safety

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 29 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 : October 2017
Actual Study Completion Date : October 31, 2017

Resource links provided by the National Library of Medicine

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

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

Information from the National Library of Medicine

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

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01708707

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United States, Arizona
Banner - University Medical Center Phoenix
Phoenix, Arizona, United States, 85006
Sponsors and Collaborators
Mednax Center for Research, Education, Quality and Safety
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Principal Investigator: Gregory Martin, MD Banner University Medical Center
Publications automatically indexed to this study by Identifier (NCT Number):
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Responsible Party: Mednax Center for Research, Education, Quality and Safety Identifier: NCT01708707    
Other Study ID Numbers: Banner IRB 01-13-0030
First Posted: October 17, 2012    Key Record Dates
Last Update Posted: August 15, 2018
Last Verified: March 2018
Additional relevant MeSH terms:
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Neonatal Abstinence Syndrome
Substance Withdrawal Syndrome
Pathologic Processes
Substance-Related Disorders
Chemically-Induced Disorders
Mental Disorders
Infant, Newborn, Diseases
Analgesics, Opioid
Central Nervous System Depressants
Physiological Effects of Drugs
Sensory System Agents
Peripheral Nervous System Agents
Narcotic Antagonists