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

NCT ID: NCT04214834

Last Updated: 2025-03-13

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: PHASE3
• Total Enrollment: 189 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-09-28
• Study Completion Date: 2026-06-30

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.

Conditions

Neonatal Opioid Withdrawal Syndrome

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Rapid-wean

15% decrements from the stabilization dose of morphine/methadone

Group Type: ACTIVE_COMPARATOR

Morphine

Intervention Type: DRUG

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.

Methadone

Intervention Type: DRUG

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.

Slow-wean

10% decrements from the stabilization dose of morphine/methadone

Group Type: ACTIVE_COMPARATOR

Morphine

Intervention Type: DRUG

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.

Methadone

Intervention Type: DRUG

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.

Interventions

Morphine

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.

Intervention Type: DRUG

Methadone

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.

Intervention Type: DRUG

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

• Minimum Eligible Age: 36 Weeks
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

NIH

Sponsor Role: collaborator

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

NETWORK

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Abhik Das, PhD

Role: PRINCIPAL_INVESTIGATOR

RTI International

Abbot Laptook, MD

Role: PRINCIPAL_INVESTIGATOR

Women and Infants Hospital of Rhode Island

Adam Czynski, DO

Role: PRINCIPAL_INVESTIGATOR

Connecticut Children's Medical Center

Locations

University of Alabama at Birmingham

Birmingham, Alabama, United States

University of Arizona

Tucson, Arizona, United States

University of Arkansas Medical Sciences

Little Rock, Arkansas, United States

Loma Linda University Medical Center

Loma Linda, California, United States

Sharp Mary Birch Hospital for Women and Newborns

San Diego, California, United States

University of Iowa

Iowa City, Iowa, United States

Ochsner Medical Regional Hospital

Kenner, Louisiana, United States

Tulane University Health Science Center

New Orleans, Louisiana, United States

Ochsner Baptist Clinical Trials Unit

New Orleans, Louisiana, United States

MedStar Franklin Square

Hyattsville, Maryland, United States

University of Massachusetts Memorial Medical Center-West Campus

Worcester, Massachusetts, United States

Central Michigan University

Detroit, Michigan, United States

Children's Mercy Hospital

Kansas City, Missouri, United States

Washington University School of Medicine

St Louis, Missouri, United States

University of New Mexico

Albuquerque, New Mexico, United States

RTI International

Durham, North Carolina, United States

Metrohealth

Cleveland, Ohio, United States

Nationwide Childeren's Hospital

Columbus, Ohio, United States

Ohio State University Hospital

Columbus, Ohio, United States

Women & Infants Hospital of Rhode Island

Providence, Rhode Island, United States

Sanford Health

Sioux Falls, South Dakota, United States

University of Tennessee Health Science Center

Memphis, Tennessee, United States

The University of Tennessee Health Science Center

Memphis, Tennessee, United States

West Virginia University Hospital

Morgantown, West Virginia, United States

Countries

United States

References

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.

Reference Type: DERIVED

PMID: 37480087 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Document Type: Informed Consent Form: ICF Template

View Document

Document Type: Informed Consent Form: Parental Informed Consent and Assent

View Document

Document Type: Informed Consent Form: Caregiver-only Consent

View Document

Document Type: Informed Consent Form: Infant-only Consent

View Document

Other Identifiers

ACTNOW-02

Identifier Type: -

Identifier Source: org_study_id