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

Advancing Clinical Trials in Neonatal Opioid Withdrawal (ACT NOW) Program

Status and phase: Active, not recruiting; Phase 3

Conditions: Neonatal Opioid Withdrawal Syndrome

Treatments: Drug: Morphine; Drug: Methadone

Study type: Interventional

Funder types: NETWORK; NIH

Identifiers

NCT04214834

ACTNOW-02

Details and patient eligibility

About

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).

Full 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.

Enrollment: 189 patients

Sex: All

Ages: 36+ weeks old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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189 participants in 2 patient groups

Rapid-wean

Active Comparator group

Description:

15% decrements from the stabilization dose of morphine/methadone

Treatment:

Drug: Methadone

Drug: Morphine

Slow-wean

Active Comparator group

Description:

10% decrements from the stabilization dose of morphine/methadone

Treatment:

Drug: Methadone

Drug: Morphine