Trial to Shorten Pharmacologic Treatment of Newborns With Neonatal Opioid Withdrawal Syndrome (NOWS)
Pragmatic, Randomized, Blinded Trial to Shorten Pharmacologic Treatment of Newborns With Neonatal Opioid Withdrawal Syndrome (NOWS)
1 other identifier
interventional
189
1 country
24
Brief Summary
The objective of this study is to evaluate the efficacy of a rapid wean intervention compared with a slow-wean intervention in reducing the number of days of opioid treatment from the first dose of weaning to cessation of opioid among infants receiving an opioid (defined as morphine or methadone) as the primary treatment for neonatal opioid withdrawal syndrome (NOWS).
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P25-P50 for phase_3
Started Sep 2020
Longer than P75 for phase_3
24 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
December 5, 2019
CompletedFirst Posted
Study publicly available on registry
January 2, 2020
CompletedStudy Start
First participant enrolled
September 28, 2020
CompletedPrimary Completion
Last participant's last visit for primary outcome
January 31, 2024
CompletedResults Posted
Study results publicly available
March 13, 2025
CompletedStudy Completion
Last participant's last visit for all outcomes
June 30, 2026
ExpectedMarch 13, 2025
January 1, 2025
3.3 years
December 5, 2019
January 31, 2025
February 25, 2025
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Days of Opioid Treatment From First Wean to Cessation
The number of days of opioid treatment (used as primary treatment), including escalation, resumption, and spot treatment, from the first weaning dose to cessation of opioid. From the start of opioid study medication until weaning. Infants will exit the study intervention without unblinding (remain in the trial) if they have not weaned off study drug by 35 days (inclusive of the 35th day) form the first weaning dose. Outcome will be truncated at 35 days regardless of the study arm.We note that primary outcome data is missing for 4 participants resulting in total sample of 185 for the primary analysis.
From the start of opioid study medication until weaning. Infants exited the study intervention without unblinding (remained in the trial) by 35 days from the first weaning dose. Outcome truncated at 35 days regardless of the study arm.
Secondary Outcomes (3)
Days of Opioid Treatment From First Wean to Cessation Among Infants That Were Not Withdrawn in High Enrolling Centers
From the start of opioid study medication until weaning. Infants exited the study intervention without unblinding (remained in the trial) by 35 days from the first weaning dose. Outcome truncated at 35 days regardless of the study arm.
Days of Opioid Treatment From First Wean to Cessation Among High Enrolling Centers
From the start of opioid study medication until weaning. Infants exited the study intervention without unblinding (remained in the trial) by 35 days from the first weaning dose. Outcome truncated at 35 days regardless of the study arm.
Days of Opioid Treatment From First Wean to Cessation Among Infants That Were Not Withdrawn
From the start of opioid study medication until weaning. Infants exited the study intervention without unblinding (remained in the trial) by 35 days from the first weaning dose. Outcome truncated at 35 days regardless of the study arm.
Study Arms (2)
Rapid-wean
ACTIVE COMPARATOR15% decrements from the stabilization dose of morphine/methadone
Slow-wean
ACTIVE COMPARATOR10% decrements from the stabilization dose of morphine/methadone
Interventions
The dose interval for morphine will be either every 3 or 4 hours, per hospital practice. Clinical teams are asked to wean study drug at least every 24 hours.
The dose interval for methadone will be every 8 or 12 hours, per hospital practice. Clinical teams are asked to wean study drug at least every 24 hours.
Eligibility Criteria
You may qualify if:
- Hospital Level
- Hospital provides pharmacologic treatment to at least an average of 12 opioid exposed infants each year
- Hospital uses a scoring system to assess for signs of NOWS (original or modified Finnegan Neonatal Abstinence Scoring system, Eat-Sleep or Console)
- Hospital provides opioid replacement therapy with either morphine or methadone as part of pharmacologic treatment of NOWS
- Infant Level
- Gestational age ≥ 36 weeks
- Receiving scheduled pharmacological therapy with morphine or methadone as the primary drug treatment for NOWS secondary to maternal opioid use
- Tolerating enteral feeds and medications by mouth
You may not qualify if:
- Hospital Level
- \. Hospitals discharge \> 10% of infants from the hospital on opioid replacement therapy on average per year
- Infant Level
- Major birth defect (e.g. gastroschisis)
- Hypoxic-ischemic encephalopathy
- Seizures from etiologies other than NOWS
- Treatment with opioids for reasons other than NOWS
- Respiratory support (nasal cannula or greater) for \> 72 hours
- Planned discharge from the hospital on opioids
- Use of other opioids (e.g., buprenorphine) as primary drugs for treatment of NOWS
- Weaning of morphine or methadone as the primary treatment of NOWS has started
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (24)
University of Alabama at Birmingham
Birmingham, Alabama, 35249, United States
University of Arizona
Tucson, Arizona, 85724, United States
University of Arkansas Medical Sciences
Little Rock, Arkansas, 72202, United States
Loma Linda University Medical Center
Loma Linda, California, 92354, United States
Sharp Mary Birch Hospital for Women and Newborns
San Diego, California, 92123, United States
University of Iowa
Iowa City, Iowa, 52242, United States
Ochsner Medical Regional Hospital
Kenner, Louisiana, 70065, United States
Tulane University Health Science Center
New Orleans, Louisiana, 70001, United States
Ochsner Baptist Clinical Trials Unit
New Orleans, Louisiana, 70115, United States
MedStar Franklin Square
Hyattsville, Maryland, 20782, United States
University of Massachusetts Memorial Medical Center-West Campus
Worcester, Massachusetts, 01605, United States
Central Michigan University
Detroit, Michigan, 48201, United States
Children's Mercy Hospital
Kansas City, Missouri, 64108, United States
Washington University School of Medicine
St Louis, Missouri, 63110, United States
University of New Mexico
Albuquerque, New Mexico, 87131, United States
RTI International
Durham, North Carolina, 27705, United States
Metrohealth
Cleveland, Ohio, 44109, United States
Nationwide Childeren's Hospital
Columbus, Ohio, 43205, United States
Ohio State University Hospital
Columbus, Ohio, 43210, United States
Women & Infants Hospital of Rhode Island
Providence, Rhode Island, 02905, United States
Sanford Health
Sioux Falls, South Dakota, 57104, United States
University of Tennessee Health Science Center
Memphis, Tennessee, 38119, United States
The University of Tennessee Health Science Center
Memphis, Tennessee, 38163, United States
West Virginia University Hospital
Morgantown, West Virginia, 26506, United States
Related Publications (1)
Czynski A, Laptook A, Das A, Smith B, Simon A, Greenberg R, Annett R, Lee J, Snowden J, Pedroza C, Lester B, Eggleston B, Bremer D, McGowan E. Pragmatic, randomized, blinded trial to shorten pharmacologic treatment of newborns with neonatal opioid withdrawal syndrome (NOWS). Trials. 2023 Jul 21;24(1):466. doi: 10.1186/s13063-023-07378-x.
PMID: 37480087DERIVED
MeSH Terms
Interventions
Intervention Hierarchy (Ancestors)
Results Point of Contact
- Title
- Dr. Abhik Das
- Organization
- RTI International
Study Officials
- PRINCIPAL INVESTIGATOR
Abhik Das, PhD
RTI International
- PRINCIPAL INVESTIGATOR
Abbot Laptook, MD
Women and Infants Hospital of Rhode Island
- PRINCIPAL INVESTIGATOR
Adam Czynski, DO
Connecticut Children's Medical Center
Publication Agreements
- PI is Sponsor Employee
- No
- Restrictive Agreement
- No
Study Design
- Study Type
- interventional
- Phase
- phase 3
- Allocation
- RANDOMIZED
- Masking
- QUADRUPLE
- Who Masked
- PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
- Masking Details
- The pharmacy will track dose levels to know where an infant is within a rapid- or slow-wean intervention arm. The clinical team will be blinded to the dose level and will only be aware of the study steps. Both the rapid- and slow-wean intervention arms are depicted to indicate that if each intervention arm has the same number of escalations, the study steps will be identical. This is critical to maintaining the clinical team blinding.
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- NETWORK
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
December 5, 2019
First Posted
January 2, 2020
Study Start
September 28, 2020
Primary Completion
January 31, 2024
Study Completion (Estimated)
June 30, 2026
Last Updated
March 13, 2025
Results First Posted
March 13, 2025
Record last verified: 2025-01
Data Sharing
- IPD Sharing
- Will share
- Shared Documents
- STUDY PROTOCOL, SAP, ICF
Data will be made available in NICHD Data and Specimen Hub (DASH).