Treatment of Neonatal Abstinence Syndrome (HOMENOW)

November 5, 2013 updated by: Mark S Brown, MD, Eastern Maine Medical Center

Treatment of Neonatal Abstinence Syndrome: Evaluation of Efficacy of Phenobarbital in Combination With Either Methadone or Diluted Deodorized Tincture of Opium as Stabilizing and Tapering Regiments

This study compares treatment of Neonatal Abstinence Syndrome (NAS) with two different drugs for the difference in the length of treatment. This is a randomized, open-label comparison of phenobarbital and methadone versus phenobarbital and diluted deodorized tincture of opium (dDTO) where phenobarbital is the initial drug used to stabilize neonatal withdrawal.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

a.Procedures: NAS scoring is currently done on infants meeting the inclusion criteria [IDD 29:070]. NAS scores are initially done every 2 hours for 24 hours and then every 4 hours when awake or before feeding for the duration of observation or treatment.

i. NAS scores may indicate more than withdrawal. Conditions such as colic, reflux, or baseline irritability may influence the baseline scores. Decisions made based on the NAS scores should take into account these factors and the baseline for the infant.

b.Emergence of symptom, dosing, and initiation of treatment: Withdrawal is defined as at least 2 NAS scores >8 or 1 NAS score >12. Once withdrawal has emerged, the infant will be given: i. Phenobarbital 20 to 30 mg/kg to load divided in up to 3 doses over 24 hours and maintenance phenobarbital should be started at 2.5 mg/kg/dose administered Q 12h, 12 hours after the loading dose is ended. NAS scoring is continued and if scores remain <8 for a minimum of 5 days after starting phenobarbital, the infant is eligible for discharge.

ii. If after phenobarbital treatment has been started, at least 2 NAS scores >8 or 1 NAS score >12, then a phenobarbital level will be drawn and a mini-load calculated to reach a level of 30 mg/dl. If withdrawal is not controlled or re-emerges after the mini-load dose, the infant will be randomized to one of the two arms of the study - methadone or dDTO.

iii. Twins will be randomized together to the same arm. iv. Randomization will be stratified into mothers on narcotic treatment >3 months and those not in treatment or <3 months. Randomization will be done in blocks of 10 for each stratum.

v. For both drugs, the neonatal preparation will be used. vi. The following is a dosing guide for methadone:

  1. The neonatal concentration is 1 mg/ml of methadone. It is administered orally every 12 hours - standardized eventually to 0900 and 2100.

  2. For the first 24 hours, doses will be prescribed every 6 hours for 4 doses, using a sliding scale in response to the last NAS score:

    NAS Score Methadone dose 8-11 0.05 mg/kg/dose 12-15 0.1 mg/kg/dose >16 0.15 mg/kg/dose

  3. Maximum loading dose of methadone will be 0.15 mg/kg/dose Q 6 hour
  4. After the first 24 hours of treatment, the total methadone dose will be summed and that dose divided into two doses, given 12 hours apart. Subsequently, PRN doses of 0.05 mg/kg/dose may be given every 6 hours for scores >8 X 2 and added to the next 24 hour's doses, divided every 12 hours, until NAS scores are consistently <8 for 48 hours.
  5. If at any point the maximum dose of methadone is reached and withdrawal is not controlled, then in the opinion of two neonatologists the patient can be crossed-over to the dDTO arm.

vii. The following is a dosing guide for dDTO:

  1. The neonatal concentration is 1:24 dilution for a concentration of 0.4%, equivalent to 0.4 mg/ml of morphine. It is administered orally every 4 hours - standardized eventually to 0400, 0800, 1200, 1600, 2000, 0000.

  2. The starting dose is determined by using a sliding scale in response to the last NAS score before starting:

    NAS Score dDTO dose 8-11 0.1 mg/kg/day 12-15 0.15 mg/kg/day >16 0.2 mg/kg/day

    For next day, the maintenance dose will return to the previous dose and given in 6 divided doses given Q 4 hours.

    iv. For either methadone or dDTO, dosing will be held at this level and weaning will be resumed when the infant has NAS scores <8 for 48 hours.

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

    f. Behavioral assessment: Behavioral assessment will be done by two methods. The first by actigraphy and the second by NINS, both during the second week of weaning. The latter will be done prior to a scheduled phenobarbital dose.

    g. Formula: A 24 kcal/ounce formula should be fed initially using either standard formula or by adding breast milk fortifier. During the weaning period, when weight gain is >30 grams/day for at least 2 days, formula will be changed to 20 kcal/ounce and weight gain monitored. If not sustained, then formula should be changed back to 24 kcal/ounce.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
40

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • 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
    • Maine
      • Bangor, Maine, United States, 04401
        • Eastern Maine Medical 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

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

3 years to 3 years (Child)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Evidence of opioid withdrawal clinically as defined by 2 NAS scores >8 or 1 NAS score >12 over a 4 to 8 hour time period, AND
  • Gestation >=35 weeks at entry defined by best obstetrical and physical exam criteria, AND
  • Medically stable condition, other than in opioid withdrawal, in the opinion of the attending neonatologist, AND EITHER,
  • Meconium or urine drug screen positive for opioids on mother or newborn, OR
  • Known maternal prescription of opioids for chronic pain management during at least the last trimester of pregnancy, OR
  • Known maternal prescription of opioids for treatment of addiction, OR
  • Suspected or admitted abuse with opioid drugs
  • Infants of mothers with a medical or psychiatric diagnosis will not be excluded, unless the maternal diagnosis precludes informed consent

Exclusion Criteria:

  • Gestation <35 weeks at entry defined by best obstetrical and physical exam criteria.
  • Hypoglycemia, hypomagnesaemia, or hypocalcaemia until corrected.
  • Serious medical illness such as sepsis, pneumonia, hyperthyroidism, meningitis, intracranial hemorrhage, perinatal depression, or respiratory failure requiring admission to the NICU.
  • Evidence of major congenital anomalies or genetic syndromes that impact the neonatal course.

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

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Active Comparator: 1 (Phenobarbital and Methadone)

The following is a dosing guide for methadone:

  1. The neonatal concentration is 1 mg/ml of methadone. It is administered orally every 12 hours.

  2. For the first 24 hours, doses will be prescribed every 6 hours using a sliding scale in response to the last NAS score:

    NAS Score Methadone dose 8-11 0.05 mg/kg/dose 12-15 0.1 mg/kg/dose

    ≥16 0.15 mg/kg/dose

  3. Maximum dose of methadone will be 0.15 mg/kg/dose.
  4. After the first 24 hours of treatment, the total methadone dose will be summed and that dose divided into two doses, given 12 hours apart. For the following 24 hours, additional doses may be given every 6 hours as needed and added to the next 24 hour's doses divided every 12 hours, until NAS scores are consistently <8 for 48 hours.
  5. If at any pointthe maximum dose of methadone is reached and withdrawal is not controlled, then in the opinion of two neonatologists the patient can be crossed-over to the dDTO arm.
Drug: Methadone
Concentration is 1mg/mL administered every 12 hours given on sliding scale in response to last NAS score.
Other Names:
  • Dolophine
Active Comparator: 2 (Phenobarbital and Diluted Deodorized Tincture of Opium)

The following is a dosing guide for dDTO:

  1. The neonatal concentration is 1:24 dilution for a concentration of 0.4%, equivalent to 0.4 mg/ml of morphine. It is administered orally every 4 hours.

  2. The starting dose will be determined using a sliding scale in response to the last NAS score before starting.

    NAS Score Starting dDTO dose 8-11 0.4 mg/kg/day 12-15 0.6 mg/kg/day

    ≥16 0.8 mg/kg/day

  3. The maximum dose of DTO will be 0.8 mg/kg/day.
  4. After the first 24 hours of treatment, if the NAS scores are still ≥8, the dose will be increased to the next level.
  5. If at any point the maximum dose of methadone is reached and withdrawal is not controlled, then in the opinion of two neonatologists the patient can be crossed-over to the methadone arm.
Drug: Diluted Deodorized Tincture of Opium
Concentration is 1:24 dilution for a concentration of 0.4%
Other Names:
  • Laudanum

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Length of Treatment With Opioid Medication
Time Frame: Up to 12 months
Up to 12 months
Up to 12 months

Collaborators and Investigators

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

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Eastern Maine Medical Center

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Mark S. Brown, MD, Eastern Maine Medical Center

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

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
January 1, 2007

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
September 1, 2009

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
September 1, 2009

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
January 27, 2011

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
November 6, 2012

First Posted (Estimate)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
November 8, 2012

Study Record Updates

Last Update Posted (Estimate)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
November 27, 2013

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
November 5, 2013

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
November 1, 2013

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 07-2-M-107

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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