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

NCT ID: NCT01708707

Last Updated: 2018-08-15

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 29 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2012-12-31
• Study Completion Date: 2017-10-31

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).

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.

Conditions

Neonatal Abstinence Syndrome; Neonatal Withdrawal Syndrome

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

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

Group Type: ACTIVE_COMPARATOR

Morphine Sulfate

Intervention Type: DRUG

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.

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

Group Type: EXPERIMENTAL

Buprenorphine

Intervention Type: DRUG

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.

Interventions

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.

Intervention Type: 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.

Intervention Type: DRUG

Other Intervention Names

Sublingual buprenorphine; Other Name: Buprenex (buprenorphine); NDC Number: 12496-0757-1; Product Code: 12496-0757; Oral Morphine Sulfate; Morphine; NDC: 0406-8003-24

Eligibility 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

• Maximum Eligible Age: 1 Year
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Pediatrix

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Gregory Martin, MD

Role: PRINCIPAL_INVESTIGATOR

Banner University Medical Center

Locations

Banner - University Medical Center Phoenix

Phoenix, Arizona, United States

Countries

United States

References

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.

Reference Type: DERIVED

PMID: 34231914 (View on PubMed)

Other Identifiers

Banner IRB 01-13-0030

Identifier Type: -

Identifier Source: org_study_id