Comparison Between Methadone and Morphine for Neonatal Opiate Withdrawal (NAS)

August 31, 2017 updated by: Mark S Brown, MD, Eastern Maine Medical Center

Evaluation of Efficacy of Methadone Versus Morphine for Treatment of Neonatal Abstinence Syndrome (NAS).

Hypothesis is that the effectiveness of opiate treatment with morphine will result in shorter duration of opiate medication treatment and fewer infants treated with a second drug.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

The purpose is to compare treatment of NAS with two different initial medications with primary outcome of (1) reducing the duration of opiate medication treatment and (2) reducing the number of infants treated with a second medication.

Design is a randomized, blinded comparison. The comparison is between methadone and morphine

Research Design:

a. Procedures: NAS scoring is currently done on infants meeting the inclusion criteria. NAS scores are done every 2 hours for 24 hours and then every 4 hours when awake after feeding for the duration of observation and treatment.

i. NAS scores may indicate more than withdrawal. Conditions such as colic (hypercaloric formula, transient lactose intolerance), reflux, diaper irritation, prenatal SSRI exposure, and nicotine withdrawal or baseline irritability may influence the variability of scores. Decisions based on the NAS scores should take into account these factors for the infant.

b. Emergence of symptom, dosing, and initiation of treatment: Withdrawal significant enough to warrant consideration for treatment is defined as 2 NAS scores >8. Once this threshold has been reached and consent obtained, the infant is randomized to treatment arm, stratified for prenatal exposure to methadone or buprenorphine. Twins will be randomized together to the same arm. The treatment arms are either: i. Methadone (1 mg/mL) or morphine (1 mg/mL) administered orally every 4 hours. The following is a dosing guide:

NAS Score Methadone or Morphine 8-12 0.05 mg/kg/dose >13 0.1 mg/kg/dose

  1. Maximum dose of methadone or morphine will be 0.2 mg/kg/dose. (NeoFax)
  2. Additional doses, 0.05 mg/kg, may be given every 12 hours as needed and added to the next 24 hour's doses divided every 4 hours, until NAS scores are consistently <8 for 48 hours.

  3. If the maximum dose of methadone or morphine is reached and if withdrawal is not controlled, the infant will be started on clonazepam (0.005 mg/kg/dose q 12h) per current treatment.

    c. Tapering medications: When the infant has NAS scores consistently <8 for 36 hours: i.The taper will be on a daily basis of 10% of the final maintenance dose. Dosages will be decreased in a measured amount to maintain NAS scores <8. After the last dose, there will be a 24 to 36 hour observation period.

    d.Non-tolerance of tapering: Non-tolerance of tapering is defined as 2 NAS scores >8 during the 12 hour period prior to the next taper dose: i.The tapering should be stopped at the current level. ii.If necessary, an extra dose of methadone or morphine can be given and added to the next day's dose divided into 6 doses. If withdrawal re-emerges after this dose (2 NAS scores >8), then the maintenance dose should be increased back to the last level; an extra dose may be given up to 4 to 5 hours after the previous dose.

    iii. If an extra dose is not given, the wean schedule can be resumed after 24 hours of NAS scores <8; when dosing is resumed, the frequency should be changed to every 4 hours with the same total daily dose.

    e. Holding of doses: Methadone or morphine will be held for poor feeding, respiratory depression, or somnolence at any time in the protocol.

Study Type

Interventional

Enrollment (Actual)

31

Phase

  • Phase 4

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

2 hours to 4 weeks (Child)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

i. Evidence of opioid withdrawal clinically defined by at least 2 NAS scores > 8 in an 8 hour time period, AND

ii. Gestation => 35 weeks at entry defined by best obstetrical and physical exam criteria, AND

iii. Medically stable condition in the opinion of the attending neonatologist, other than opiate withdrawal, AND

iv. Mother on opiate replacement treatment therapy - methadone or buprenorphine.

Exclusion Criteria:

i. Gestation < 35 weeks at entry defined by best obstetrical and physical exam criteria.

ii. Hypoglycemia, hypomagnesaemia, or hypocalcemia until corrected,

iii. Serious medical illness such as sepsis, pneumonia, thyroid dysfunction, meningitis, intracranial hemorrhage, perinatal depression, or respiratory failure requiring admission to the NICU.

iv. Evidence of major congenital anomalies or genetic syndromes that impact the neonatal course

v. Mother consistently taking prescribed benzodiazepine at the time of delivery

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: Double

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: methadone

Methadone (1 mg/mL) administered orally every 4 hours. The following is a dosing guide:

NAS Score Methadone 8-12 0.05 mg/kg/dose >=13 0.1 mg/kg/dose

  1. Maximum dose of methadone will be 0.2 mg/kg/dose. (NeoFax)
  2. Additional doses, 0.05 mg/kg, may be given every 4 hours as needed and added to the next 24 hour's doses divided every 4 hours, until NAS scores are consistently <8 for 48 hours.
  3. If the maximum dose of methadone is reached and if withdrawal is not controlled, the infant will be started on clonazepam (0.005 mg/kg/dose q 12h) per current treatment.
Drug: Methadone
To compare the duration of opiate medication treatment for babies on methadone versus those on morphine.
Other Names:
  • see arm/group descriptions
Active Comparator: morphine

Morphine (1 mg/mL) administered orally every 4 hours. The following is a dosing guide:

NAS Score Morphine 8-12 0.05 mg/kg/dose >=13 0.1 mg/kg/dose

  1. Maximum dose of morphine will be 0.2 mg/kg/dose. (NeoFax)
  2. Additional doses, 0.05 mg/kg, may be given every 4 hours as needed and added to the next 24 hour's doses divided every 6 hours, until NAS scores are consistently <8 for 48 hours.
  3. If the maximum dose of morphine is reached and if withdrawal is not controlled, the infant will be started on clonazepam (0.005 mg/kg/dose q 12h) per current treatment.
Drug: Morphine
To compare the duration of opiate medication treatment for babies on methadone versus those on morphine.
Other Names:
  • see arm/group descriptions

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Days of Treatment With Opioid Medication
Time Frame: From date of randomization until the date of last opioid dose or date of death from any cause, whichever came first, assessed up to 12 months
The length of time in days that the treatment opioid was used on a measured taper to ameliorate withdrawal signs
From date of randomization until the date of last opioid dose or date of death from any cause, whichever came first, assessed up to 12 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Second Drug for Withdrawal
Time Frame: From date of randomization until the date of last opioid dose or date of death from any cause or date of discharge, whichever came first, assessed up to 12 months
Number of infants treated with a second drug to treat their withdrawal
From date of randomization until the date of last opioid dose or date of death from any cause or date of discharge, whichever came first, assessed up to 12 months

Collaborators and Investigators

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

Sponsor

Eastern Maine Medical Center

Investigators

  • Principal Investigator: Mark Brown, MD, Eastern Maine Medical Center

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

January 1, 2011

Primary Completion (Actual)

October 1, 2012

Study Completion (Actual)

October 1, 2012

Study Registration Dates

First Submitted

November 6, 2012

First Submitted That Met QC Criteria

March 1, 2013

First Posted (Estimate)

March 5, 2013

Study Record Updates

Last Update Posted (Actual)

September 28, 2017

Last Update Submitted That Met QC Criteria

August 31, 2017

Last Verified

August 1, 2017

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 10-1-M-185

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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