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

Primary Purpose

Neonatal Abstinence Syndrome, Neonatal Withdrawal Syndrome

Status

Completed

Phase

Phase 2

Locations

United States

Study Type

Interventional

Intervention

Buprenorphine

Morphine Sulfate

About this trial

This is an interventional treatment trial for Neonatal Abstinence Syndrome

Eligibility Criteria

undefined - 1 Year (Child)All SexesDoes not accept healthy volunteers

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

Sites / Locations

Banner - University Medical Center Phoenix

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Experimental

Arm Label

Oral morphine sulfate

Buprenorphine

Arm Description

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

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

Outcomes

Primary Outcome Measures

Hospital length of stay

Number of days of hospital admission

Secondary Outcome Measures

Number of adverse or serious adverse events

Cost efficiency of buprenorphine

Cost of buprenorphine as a product of number of days of administration

Withdrawal symptoms

Finnegan methodology to score withdrawal symptoms every four hours of medication administration

Rescue dosage administration

Number of rescue doses of additional medication

Full Information

NCT ID

NCT01708707

First Posted

April 25, 2012

Last Updated

August 14, 2018

Sponsor

Pediatrix

1. Study Identification

Unique Protocol Identification Number

NCT01708707

Brief Title

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

Official Title

A Randomized Comparison of Sublingual Buprenorphine to Morphine Sulfate in the Treatment of Neonatal Abstinence Syndrome (NAS)

Study Type

Interventional

2. Study Status

Record Verification Date

March 2018

Overall Recruitment Status

Completed

Study Start Date

December 2012 (undefined)

Primary Completion Date

October 2017 (Actual)

Study Completion Date

October 31, 2017 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Pediatrix

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Neonatal Abstinence Syndrome, Neonatal Withdrawal Syndrome

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Parallel Assignment

Masking

ParticipantCare ProviderInvestigatorOutcomes Assessor

Allocation

Randomized

Enrollment

29 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Oral morphine sulfate

Arm Type

Active Comparator

Arm Description

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

Arm Title

Buprenorphine

Arm Type

Experimental

Arm Description

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

Intervention Type

Drug

Intervention Name(s)

Buprenorphine

Other Intervention Name(s)

Sublingual buprenorphine, Other Name: Buprenex (buprenorphine), NDC Number: 12496-0757-1, Product Code: 12496-0757

Intervention Description

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

Intervention Name(s)

Morphine Sulfate

Other Intervention Name(s)

Oral Morphine Sulfate, Morphine, NDC: 0406-8003-24

Intervention Description

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.

Primary Outcome Measure Information:

Title

Hospital length of stay

Description

Number of days of hospital admission

Time Frame

Up to hospital discharge, an anticipated average of 4 weeks

Secondary Outcome Measure Information:

Title

Number of adverse or serious adverse events

Time Frame

Up to hospital discharge, with length of stay currently averaging approximately 4 weeks

Title

Cost efficiency of buprenorphine

Description

Cost of buprenorphine as a product of number of days of administration

Time Frame

At least 48 prior to hospital discharge, with anticipated discharge averaging to be 4 weeks

Title

Withdrawal symptoms

Description

Finnegan methodology to score withdrawal symptoms every four hours of medication administration

Time Frame

Up to hospital discharge, usually occuring on average 4 weeks

Title

Rescue dosage administration

Description

Number of rescue doses of additional medication

Time Frame

Up to hospital discharge, anticipating an average of 4 weeks

10. Eligibility

Sex

All

Maximum Age & Unit of Time

1 Year

Accepts Healthy Volunteers

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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Gregory Martin, MD

Organizational Affiliation

Banner University Medical Center

Official's Role

Principal Investigator

Facility Information:

Facility Name

Banner - University Medical Center Phoenix

City

Phoenix

State/Province

Arizona

ZIP/Postal Code

85006

Country

United States

12. IPD Sharing Statement

Citations:

PubMed Identifier

34231914

Citation

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.

Results Reference

derived

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

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