Clinical trial NCT04214834: Trial to Shorten Pharmacologic Treatment of Newborns With Neonatal Opioid Withdrawal Syndrome (NOWS)
Official title: Pragmatic, Randomized, Blinded Trial to Shorten Pharmacologic Treatment of Newborns With Neonatal Opioid Withdrawal Syndrome (NOWS)
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE3
Conditions: Neonatal Opioid Withdrawal Syndrome
Keywords: NOWS
Lead sponsor: Advancing Clinical Trials in Neonatal Opioid Withdrawal (ACT NOW) Program
Sponsor class: NETWORK
Collaborators: name: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
First posted: 2020-01-02
Enrollment: 189
Sex: ALL
Minimum age (years): 36
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
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

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).

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.

Eligibility criteria: 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

Primary outcomes:
measure: Days of Opioid Treatment From First Wean to Cessation
timeFrame: 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:
measure: Days of Opioid Treatment From First Wean to Cessation Among Infants That Were Not Withdrawn in High Enrolling Centers
timeFrame: 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.
measure: Days of Opioid Treatment From First Wean to Cessation Among High Enrolling Centers
timeFrame: 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.
measure: Days of Opioid Treatment From First Wean to Cessation Among Infants That Were Not Withdrawn
timeFrame: 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.
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama at Birmingham
state: Alabama
city: Tucson
country: United States
facility: University of Arizona
state: Arizona
city: Little Rock
country: United States
facility: University of Arkansas Medical Sciences
state: Arkansas
city: Loma Linda
country: United States
facility: Loma Linda University Medical Center
state: California
city: San Diego
country: United States
facility: Sharp Mary Birch Hospital for Women and Newborns
state: California
city: Iowa City
country: United States
facility: University of Iowa
state: Iowa
city: Kenner
country: United States
facility: Ochsner Medical Regional Hospital
state: Louisiana
city: New Orleans
country: United States
facility: Tulane University Health Science Center
state: Louisiana
city: New Orleans
country: United States
facility: Ochsner Baptist Clinical Trials Unit
state: Louisiana
city: Hyattsville
country: United States
facility: MedStar Franklin Square
state: Maryland
city: Worcester
country: United States
facility: University of Massachusetts Memorial Medical Center-West Campus
state: Massachusetts
city: Detroit
country: United States
facility: Central Michigan University
state: Michigan
city: Kansas City
country: United States
facility: Children's Mercy Hospital
state: Missouri
city: Saint Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
city: Albuquerque
country: United States
facility: University of New Mexico
state: New Mexico
city: Durham
country: United States
facility: RTI International
state: North Carolina
city: Cleveland
country: United States
facility: Metrohealth
state: Ohio
city: Columbus
country: United States
facility: Nationwide Childeren's Hospital
state: Ohio
city: Columbus
country: United States
facility: Ohio State University Hospital
state: Ohio
city: Providence
country: United States
facility: Women & Infants Hospital of Rhode Island
state: Rhode Island
city: Sioux Falls
country: United States
facility: Sanford Health
state: South Dakota
city: Memphis
country: United States
facility: University of Tennessee Health Science Center
state: Tennessee
city: Memphis
country: United States
facility: The University of Tennessee Health Science Center
state: Tennessee
city: Morgantown
country: United States
facility: West Virginia University Hospital
state: West Virginia
Study officials:
affiliation: RTI International
name: Abhik Das, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Women and Infants Hospital of Rhode Island
name: Abbot Laptook, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Connecticut Children's Medical Center
name: Adam Czynski, DO
role: PRINCIPAL_INVESTIGATOR
References: