Morphine Versus Methadone for Opiate Exposed Infants With Neonatal Abstinence Syndrome

May 22, 2023 updated by: Mary Beth Sutter, University of New Mexico
This study investigates the use of methadone versus morphine wean for the treatment of neonatal abstinence syndrome for infants exposed to opioids in utero. Half of infants who require pharmacotherapy for NAS will receive a methadone wean, and half will receive a morphine wean. Length of hospital stay, length of treatment and parent satisfaction will be studied.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Neonates exposed to opiates in utero can develop a constellation of withdrawal symptoms known as neonatal abstinence syndrome (NAS). Infants with NAS are at risk for multiple medical complications including failure to thrive and seizures, they often require prolonged hospital stays and account for significant health care costs. At University of New Mexico, infants exposed to methadone or heroin in utero who develop NAS requiring pharmacologic treatment undergo a treatment wean with methadone, whereas infants exposed to buprenorphine undergo a wean with morphine. However, morphine is used frequently to treat neonatal abstinence syndrome among methadone-exposed infants throughout the US, and optimal pharmacologic treatment for NAS remains unknown. Anecdotal evidence at the investigators institution suggests that infants treated with morphine have shorter hospital stays compared to infants treated with methadone. Investigators propose a pilot randomized controlled trial to evaluate morphine vs methadone treatment of infants with in-utero methadone or heroin exposure. Specifically, length of treatment, need for additional medication to treat withdrawal, and length of hospital stay will be compared.

When women are admitted to Labor and Delivery and/or up to 12 hours postpartum, research staff will approach patients about study enrollment. Participants will be approached for study enrollment if medication list on admission includes methadone, if participants self-report methadone use prenatally, and/ or if urine drug screen is positive for methadone or opiates on admission. If women choose to enroll in the study, and their infants require treatment for NAS, their infants will be randomized and assigned a study number for treatment using the methadone or morphine protocols at the time treatment is required.

All infants will be monitored for signs of withdrawal using the standard UNM NAS scoring protocol. Standard of care at UNM is to treat infants exposed to opioids in-utero with methadone if they require pharmacologic therapy for NAS, therefore treatment will not be withheld if they choose not to enroll in the study. Standard of care is also to obtain a urine drug screen on all infants with reported exposure to opiates in pregnancy. Enrolled patients will thus undergo routine urine drug screening. The only difference from standard care with regards to the study protocol is the treatment of half of the methadone or heroin exposed infants with morphine. The morphine protocol is proven for safety and efficacy currently in buprenorphine exposed infants. Once randomized, infants will continue on the protocol until discharge. At discharge, parents will complete a patient satisfaction survey.

Study Type

Interventional

Enrollment (Actual)

61

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • New Mexico
      • Albuquerque, New Mexico, United States, 87106
        • University of New Mexico Health Sciences Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

No older than 1 year (Child)

Accepts Healthy Volunteers

No

Description

Inclusion criteria:

  • Born at University of New Mexico Hospital
  • Greater than 34 weeks gestation
  • Primary in-utero drug exposure was opioids other than buprenorphine
  • Maternal or infant urine drug screen positive for methadone and/or opioids on admission

Exclusion criteria:

  • Born prior to 34 weeks
  • Neonatal intensive care unit admission
  • Serious medical comorbidities
  • Primary substance exposure in-utero was buprenorphine, or was not opioids

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Morphine

Dose given q 3 - 4 hrs with feeds; do not exceed 4 hrs between doses Morphine (0.04mg/0.1ml)

Score Dose For Initiation 0-8 0 None 9-12 0.04 mg/dose 13-16 0.08 mg/dose 17-20 0.12 mg/dose 21-24 0.16 mg/dose 25 or above 0.20mg/dose

Morphine Maintenance/Escalation

  • Maintain dose if score 0-8
  • Increase dose by 0.02 if score is 9-12 (rescore before dosing) • Increase dose by 0.04 if score 13-16
  • Increase score by 0.06 if score 17-20

Weaning Instructions:

  • Maintain on dose 48 hrs before starting weaning
  • Wean 0.02 mg morphine every day for a score is 0-8 • Defer wean for score 9-12

Re-escalation

  • If neonate scores 9-12 re-score as described for initiation,
  • If second score is in 9-12 increase morphine 0.01 mg q3-4 hrs • If 2 consecutive scores 13-16, increase 0.02 mg q3-4 hrs
  • If 2 consecutive scores in 17-20, increase 0.04 mg q3-4 hrs etc
Drug: Morphine
Morphine wean protocol as described in arm description
Active Comparator: Methadone
Step 1: 0.7 mgs/Kg/24 hrs. divided by into six doses (q 4 hrs) is starting dose Step 2: Decrease dose by half, which is 50% of starting dose, EVERY 4 hours. Step 3: Same dose which is 50% of starting dose EVERY 6 hours. Step 4: Same dose which is 50% of starting dose EVERY 8 hours. Step 5: Same dose which is 50% of starting dose EVERY 12 hours. Step 6: Decrease dose by half, which is 25% of starting dose EVERY 12 hours. Step 7: Same dose which is 25% of starting dose q 24 hours
Drug: Methadone
Methadone wean protocol as described in arm description

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Length of Hospital Stay
Time Frame: assessed at hospital discharge, approximately 7-30 days
Number of days in hospital after birth
assessed at hospital discharge, approximately 7-30 days

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Length of Treatment
Time Frame: assessed at hospital discharge, approximately 7-30 days
assessed at hospital discharge, approximately 7-30 days
Need for Additional Agent to Treat Withdrawal, Determined by Chart Review of Medication Administration Record of Administered Medications for Withdrawal Treatment (Example: Clonidine or Phenobarbital)
Time Frame: assessed at hospital discharge, approximately 7-30 days
clonidine
assessed at hospital discharge, approximately 7-30 days
Need for Feeding Assistance, Determined by Chart Review of Discharge Summary, Specifically Evaluating for Need for Nasogastric Tube Placement or Peripheral Parenteral Nutrition.
Time Frame: assessed at hospital discharge, approximately 7-30 days
assessed at hospital discharge, approximately 7-30 days
Need for NICU Transfer, as Determined by Chart Review of Discharge Summary.
Time Frame: assessed at hospital discharge, approximately 7-30 days
assessed at hospital discharge, approximately 7-30 days
Breastfeeding Initiation and Continuation at Hospital Discharge
Time Frame: assessed at hospital discharge, approximately 7-30 days
Assessed through chart review of discharge summary documentation of method of infant feeding at time of discharge
assessed at hospital discharge, approximately 7-30 days
Total Morphine Equivalent Dose Received
Time Frame: assessed at hospital discharge, approximately 7-30 days
assessed at hospital discharge, approximately 7-30 days

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of New Mexico

Investigators

  • Principal Investigator: Mary Beth Sutter, MD, Attending Physician, Assistant Professor

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

October 1, 2016

Primary Completion (Actual)

June 1, 2018

Study Completion (Actual)

September 30, 2018

Study Registration Dates

First Submitted

July 19, 2016

First Submitted That Met QC Criteria

July 27, 2016

First Posted (Estimate)

August 1, 2016

Study Record Updates

Last Update Posted (Actual)

May 24, 2023

Last Update Submitted That Met QC Criteria

May 22, 2023

Last Verified

May 1, 2023

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 16-176

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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