Comparison of Buprenorphine to Morphine in Treatment of Neonatal Abstinence Syndrome (NAS) - Full Text View

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 Phase 3

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:

Drug Information available for: Morphine sulfate Sulfate ion Buprenorphine Buprenorphine hydrochloride

U.S. FDA Resources

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 Phoenix Children's 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

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 Phoenix Children's 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

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:	May 13, 2013
Health Authority:	United States: Food and Drug Administration

Additional relevant MeSH terms:

Neonatal Abstinence Syndrome
Substance Withdrawal Syndrome
Infant, Newborn, Diseases
Substance-Related Disorders
Mental Disorders
Buprenorphine
Morphine
Analgesics, Opioid
Analgesics

Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Pharmacologic Actions
Central Nervous System Agents
Therapeutic Uses
Central Nervous System Depressants
Narcotic Antagonists
Narcotics

ClinicalTrials.gov processed this record on June 17, 2013