Purpose

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).

Condition

Eligibility

Eligible Ages
Over 36 Weeks
Eligible Genders
All
Accepts Healthy Volunteers
No

Inclusion Criteria

  • Hospital Level 1. Hospital provides pharmacologic treatment to at least an average of 12 opioid exposed infants each year 2. Hospital uses a scoring system to assess for signs of NOWS (original or modified Finnegan Neonatal Abstinence Scoring system, Eat-Sleep or Console) 3. Hospital provides opioid replacement therapy with either morphine or methadone as part of pharmacologic treatment of NOWS - Infant Level 1. Gestational age ≥ 36 weeks 2. Receiving scheduled pharmacological therapy with morphine or methadone as the primary drug treatment for NOWS secondary to maternal opioid use 3. Tolerating enteral feeds and medications by mouth

Exclusion Criteria

  • Hospital Level 1. Hospitals discharge > 10% of infants from the hospital on opioid replacement therapy on average per year - Infant Level 1. Major birth defect (e.g. gastroschisis) 2. Any major surgery (minor surgery [e.g., circumcision, digit ligation, frenulectomy] is not an exclusion criterion) 3. Hypoxic-ischemic encephalopathy 4. Seizures from etiologies other than NOWS 5. Treatment with opioids for reasons other than NOWS 6. Respiratory support (nasal cannula or greater) for > 72 hours 7. Planned discharge from the hospital on opioids 8. Use of other opioids (e.g., buprenorphine) as primary drugs for treatment of NOWS 9. Weaning of morphine or methadone as the primary treatment of NOWS has started

Study Design

Phase
Phase 3
Study Type
Interventional
Allocation
Randomized
Intervention Model
Parallel Assignment
Intervention Model Description
The study will have two intervention arms (rapid-wean and slow-wean) with 251 morphine/methadone treated infants per intervention arm, for a total of 502 morphine/methadone treated infants.
Primary Purpose
Treatment
Masking
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description
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.

Arm Groups

ArmDescriptionAssigned Intervention
Active Comparator
Rapid-wean
15% decrements from the stabilization dose of morphine/methadone
  • Drug: Morphine
    Rapid-wean: 176 treated Slow-wean: 75 treated
  • Drug: Methadone
    Rapid-wean: 176 treated Slow-wean: 75 treated
Active Comparator
Slow-wean
10% decrements from the stabilization dose of morphine/methadone
  • Drug: Morphine
    Rapid-wean: 176 treated Slow-wean: 75 treated
  • Drug: Methadone
    Rapid-wean: 176 treated Slow-wean: 75 treated

Recruiting Locations

University of Alabama at Birmingham
Birmingham, Alabama 35233
Contact:
Namasivayam Ambalavanan, MD

University of Arkansas Medical Sciences
Little Rock, Arkansas 72202
Contact:
Clare Nesmith
nesmithclare@uams.edu

Tulane University Health Science Center
New Orleans, Louisiana 70112
Contact:
Elizabeth Lindsay
elindsay@tulane.edu

School of Medicine - Wayne State University
Detroit, Michigan 48201
Contact:
Jani Sanket
sjani@dmc.org

Children's Mercy Hospital
Kansas City, Missouri 64108
Contact:
Tamorah Lewis
trlewis@cmh.edu

Washington University School of Medicine
Saint Louis, Missouri 63110
Contact:
Hayley Friedman
friedmanh@wustl.edu

University of New Mexico
Albuquerque, New Mexico 87131
Contact:
Sherry Weitzen, MD
505-994-5300
SWeitzen@salud.unm.edu

Women & Infants Hospital of Rhode Island
Providence, Rhode Island 02905
Contact:
Abbot Laptook, MD
401-430-7421
alaptook@wihri.org

Sanford Health
Sioux Falls, South Dakota 57104
Contact:
Michelle Baack, MD
605-312-6420
michelle.baack@sanfordhealth.org

The University of Tennessee Health Science Center
Memphis, Tennessee 38163
Contact:
Ajay Talati
atalati@uthsc.edu

West Virginia University Hospital
Morgantown, West Virginia 26506
Contact:
Mark Smith
mcsmith@hsc.wvu.edu

More Details

NCT ID
NCT04214834
Status
Recruiting
Sponsor
Advancing Clinical Trials in Neonatal Opioid Withdrawal (ACT NOW) Program

Study Contact

Abhik Das, PhD
301-770-8214
adas@rti.org

Detailed Description

This will be a pragmatic, randomized, blinded trial comparing a rapid-wean intervention (15% decrements from the stabilization dose) to a slow-wean intervention (10% decrements from the stabilization dose) to determine whether rapid weaning will reduce the number of treatment days among infants receiving morphine or methadone orally as the primary treatment for NOWS. Participating hospitals must provide pharmacologic treatment to at least an average of 12 opioid exposed infants each year, use a scoring system to assess for signs of NOWS (original or modified Finnegan Neonatal Abstinence Scoring system, Eat-Sleep or Console), and provide opioid replacement therapy with either morphine or methadone as the primary drug for treating NOWS. Hospitals may change use of these two opioids during the trial period. The investigators will stratify randomization by hospital. The study protocol will commence after NOWS signs have been controlled with an opioid (stabilization) and weaning of pharmacologic treatment is to be started. At or before each 24-hour interval, clinical team members will evaluate and score infants, per hospital practice, for signs of NOWS to determine if the infant will tolerate weaning of the study drug. After study drug cessation, the clinical team will observe infants in the hospital for at least 48 hours prior to discharge, which is similar to clinical practice. A trained examiner will administer the Neonatal Intensive Care Unit (NICU) Network Neurobehavioral Scale (NNNS) to assess neurobehavioral profiles after infants cease study drug and prior to discharge. At one month post discharge, primary caregivers will complete the Brief Symptom Inventory (BSI), the Maternal Postnatal Attachment Questionnaire (MPAQ) and a caregiver questionnaire. The site research team will contact the primary caregiver(s) to update contact information and/or complete questionnaires when the infant is 6 months, 12 months, 18 months, and 24 months of age. The questionnaires will assess infant wellness, neurobehavioral functioning and development, postnatal attachment and bonding, and caregiver well-being. At 24 months, the infants will be seen during which a, certified developmental specialists, blinded to the intervention, will administer the Bayley Scales of Infant and Toddler Development, Fourth Edition (Bayley-4) to assess infant neurodevelopment. The BSI and the Brief Infant Toddler Social Emotional Assessment (BITSEA) will also be administered during the 24 month visit along with measures of growth.

Notice

Study information shown on this site is derived from ClinicalTrials.gov (a public registry operated by the National Institutes of Health). The listing of studies provided is not certain to be all studies for which you might be eligible. Furthermore, study eligibility requirements can be difficult to understand and may change over time, so it is wise to speak with your medical care provider and individual research study teams when making decisions related to participation.