Randomized Control Trial of Buprenorphine vs. Morphine for the Treatment of Neonatal Opioid Withdrawal Syndrome (NOWS)

June 20, 2023 updated by: James Padbury, Women and Infants Hospital of Rhode Island

Prospective Randomized Blinded Trial to Shorten Pharmacologic Treatment of Newborns With Neonatal Opioid Withdrawal Syndrome (NOWS)

This randomized control trial will compare buprenorphine and morphine, two currently used medications for the treatment of neonatal opioid withdrawal syndrome (NOWS), in newborns to determine which medication will reduce the number of days of pharmacological treatment.

Study Overview

Status

Status

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Withdrawn

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

This randomized control trial will compare buprenorphine to morphine, two currently used medications for the treatment of NOWS, to determine whether the use of buprenorphine for NOWS treatment will reduce the number of days of pharmacological treatment. After an infant is born they will be monitored for signs of NOWS. Once an infant reaches treatment thresholds, they will be randomized using a double dummy design to either the buprenorphine or morphine treatment arm. After randomization infants will receive a syringe with either morphine or placebo every 4 hours and every 8 hours infant will receive 1 sublingual application of buprenorphine or placebo. To maintain the blind infants enrolled in the study will receive both interventions. During the study medication doses will be weaned by 10% of the stabilization dose. Study intervention will continue until 20 percent of the maximal dose has been reached. Use of a second line drug will be permissible after randomization and after an infant has had 2 consecutive escalations. Second line drug will be phenobarbital, in addition to the study drug. Infants in both groups will be evaluated and scored for NOWS symptoms to determine if weaning study medication is permissible each day. NOWS scores that do not reach the threshold for escalation will wean in accordance with standard clinical practice. If NOWS symptoms increase during treatment, infants will have the dose of the study drug increased by 10% to the previous day's dose. When stable for 24 hours, the weaning process will continue. The NICU Network Neurobehavioral Scale (NNNS) will be administered prior to starting study medication and once off study medication but prior to discharge to examine proportion of infants in each medication arm for the abnormal NNNS profiles which has been associated with atypical early childhood outcomes including behavior problems and low IQ scores. Development at 18 months of age will also be assessed to examine any differences in both arms of the study.

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

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 3

Contacts and Locations

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

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Contact Backup

Study Locations

  • United States
    • Rhode Island
      • Providence, Rhode Island, United States, 02905
        • Women and Infants Hospital

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

14 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  1. Infant gestational age greater than or equal 36 weeks
  2. Mother receiving either methadone from a drug treatment program, buprenorphine from a licensed physician, or an opioid prescription for a documented medical need
  3. Mother had at least 2 prenatal appointments.
  4. Infant toleration of oral medication administration
  5. Infant is considered medically stable by the attending physician
  6. Singleton Pregnancy
  7. English Speaking

Exclusion Criteria:

  1. Within 30 days of birth the mother has actively used illicit drugs (excluding THC) or obtaining oral opioids, methadone, or buprenorphine from a non-licensed physician or drug treatment program
  2. The mother has had less than 2 prenatal care visits
  3. The mother reports excessive alcohol use during pregnancy
  4. Mother is less than 18 years of age or is not capable of signing consent
  5. The infant has a gestational age less than or equal to 35 weeks and 6 days
  6. The infant has dysmorphic features including evidence of aneuploidy
  7. The infant is not able to tolerate oral medication administration
  8. Multiple gestation pregnancy
  9. Hypoxic-ischemic encephalopathy
  10. Seizures from etiologies other than NOWS
  11. Non-English Speaking
  12. Infant started on NOWS standard care medication prior to study consent

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: Quadruple

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: Morphine
Infants randomized to the morphine arm will start at a dose of 0.06 mg/kg/dose every 4 hours. A buprenorphine placebo will also be given at the same frequency as a faux drug.
Drug: Buprenorphine or Placebo
The double blind, double dummy design necessitates that both drugs be on an identical schedule. The 4-hour dosing allows for this pairing. If a patient is randomized to the buprenorphine arm, medication administration will follow an every 8-hour dosing but medication will be substituted with placebo during the intermediary time point.
Drug: Morphine or Placebo
If a patient is randomized to the morphine arm, morphine will be given every 4 hours. Placebo will also be given at the same frequency as a faux drug.
Experimental: Buprenorphine

Infants randomized to the buprenorphine arm will be started on a dose of 10 mg/kg/dose every 8 hours. A morphine placebo will also be given at the same frequency as a faux drug.

Patients can only be randomized to only one arm.
Drug: Buprenorphine or Placebo
The double blind, double dummy design necessitates that both drugs be on an identical schedule. The 4-hour dosing allows for this pairing. If a patient is randomized to the buprenorphine arm, medication administration will follow an every 8-hour dosing but medication will be substituted with placebo during the intermediary time point.
Drug: Morphine or Placebo
If a patient is randomized to the morphine arm, morphine will be given every 4 hours. Placebo will also be given at the same frequency as a faux drug.

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
Total amount of opioid medication for treatment of NOWS
Time Frame: Duration of pharmacological treatment with opioid medication while admitted to the hospital up to 30 days
Total amount of opioid medication given to infant for the duration of their hospitalization
Duration of pharmacological treatment with opioid medication while admitted to the hospital up to 30 days

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Length of total stay
Time Frame: During hospitalization for NOWS up to 30 days
Length of hospital stay due to NOWS
During hospitalization for NOWS up to 30 days
Length of stay secondary to NOWS
Time Frame: During hospitalization for NOWS up to 30 days
Total length of hospital stay secondary to NOWS
During hospitalization for NOWS up to 30 days
Neurobehavioral Profile
Time Frame: At birth before randomization to NOWS treatment arm around 18-24 hours of life and prior to hospital discharge up to 30 days of life
Neurobehavior will be assessed with Neonatal Intensive Care Unit (NICU) Network Neurobehavioral Scale (NNNS). The NNNS is a comprehensive evaluation of neurologic and behavioral functioning as well as signs of stress. Profile 5 is the most atypical, and is characterized by exaggerated scores for arousal, excitability, hypertonicity, quality of movement, and stress abstinence. The atypical profile as been associated with atypical early childhood outcomes, including more behavior problems and lower IQ scores. Researchers will compare the proportion of atypical neurobehavioral profiles for infants in each intervention arm.
At birth before randomization to NOWS treatment arm around 18-24 hours of life and prior to hospital discharge up to 30 days of life
Cognitive, Language, and Motor Development From 18 Month Old Bayley Neurodevelopmental Assessment
Time Frame: 18 months old
The Bayley Scales of Infant and Toddler Development (BSID-III) assesses the development of infants and children (1-42 months) through a series of developmental play tasks, identifying children with developmental delay. Raw scores of completed items are summarized within three distinct scale scores (Cognitive Scale, Language Scale, Motor Scale). Scale scores are each converted to composite scores to determine the child's performance compared with scores of age-matched children of typical development (percentile rank). A higher composite score indicates more ideal developmental outcome (range 40-160). At 18 month follow-up visit, participants were assessed using the BSID-III for composite score outcomes.
18 months old

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.
Women and Infants Hospital of Rhode Island

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
National Institute of General Medical Sciences (NIGMS)

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: Adam J Czynski, DO, Women and Infants Hospital

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 (Actual)

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.
October 1, 2020

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.
May 17, 2021

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.
May 17, 2021

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).
June 8, 2020

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.
June 30, 2020

First Posted (Actual)

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.
July 2, 2020

Study Record Updates

Last Update Posted (Actual)

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.
June 22, 2023

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.
June 20, 2023

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.
June 1, 2023

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.
  • WIH 19-0042
  • 1P20GM125507-01 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

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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