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

This study is enrolling participants by invitation only.
Sponsor:
Information provided by (Responsible Party):
Pediatrix Medical Group
ClinicalTrials.gov Identifier:
NCT01708707
First received: April 25, 2012
Last updated: September 5, 2013
Last verified: September 2013
  Purpose

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 Intervention Phase
Neonatal Abstinence Syndrome
Neonatal Withdrawal Syndrome
Drug: Buprenorphine
Drug: Morphine Sulfate
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Randomized Comparison of Sublingual Buprenorphine to Morphine Sulfate in the Treatment of Neonatal Abstinence Syndrome (NAS)

Resource links provided by NLM:


Further study details as provided by Pediatrix Medical Group:

Primary Outcome Measures:
  • Hospital length of stay [ Time Frame: Up to hospital discharge, an anticipated average of 4 weeks ] [ Designated as safety issue: No ]
    Number of days of hospital admission


Secondary Outcome Measures:
  • Number of adverse or serious adverse events [ Time Frame: Up to hospital discharge, with length of stay currently averaging approximately 4 weeks ] [ Designated as safety issue: Yes ]
  • Cost efficiency of buprenorphine [ Time Frame: At least 48 prior to hospital discharge, with anticipated discharge averaging to be 4 weeks ] [ Designated as safety issue: No ]
    Cost of buprenorphine as a product of number of days of administration

  • Withdrawal symptoms [ Time Frame: Up to hospital discharge, usually occuring on average 4 weeks ] [ Designated as safety issue: No ]
    Finnegan methodology to score withdrawal symptoms every four hours of medication administration

  • Rescue dosage administration [ Time Frame: Up to hospital discharge, anticipating an average of 4 weeks ] [ Designated as safety issue: No ]
    Number of rescue doses of additional medication


Estimated Enrollment: 64
Study Start Date: December 2012
Estimated Study Completion Date: December 2014
Estimated Primary Completion Date: December 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

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.

  Eligibility

Ages Eligible for Study:   up to 1 Year
Genders Eligible for Study:   Both
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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01708707

Locations
United States, Arizona
Banner Good Samaritan Medical Center NICU
Phoenix, Arizona, United States, 85006
Sponsors and Collaborators
Pediatrix Medical Group
Investigators
Principal Investigator: Gregory Martin, MD Banner Good Samaritan Medical Center
  More Information

No publications provided

Responsible Party: Pediatrix Medical Group
ClinicalTrials.gov Identifier: NCT01708707     History of Changes
Other Study ID Numbers: Banner IRB 01-13-0030
Study First Received: April 25, 2012
Last Updated: September 5, 2013
Health Authority: United States: Food and Drug Administration

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
Pharmacologic Actions
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Central Nervous System Agents
Therapeutic Uses
Narcotic Antagonists

ClinicalTrials.gov processed this record on September 16, 2014