Optimizing Pharmacologic Treatment for Neonatal Opioid Withdrawal Syndrome (OPTimize NOW): A Symptom-Based Dosing Approach

NCT05980260 | Completed Phase 3 DMC

• 10 other identifiers: HELP for NOWS 021U24HD1076211UG1HD1076281UG1HD1075801UG1HD1076491UG1HD1076501UG1HD1076531UG1HD1076271UG1HD1076311UG1HD107616
• Study Type: interventional
• Target: 626
• Locations: 1 country
• Sites: 23

Brief Summary

This clinical trial will help us learn more about how to best care for babies with Neonatal Opioid Withdrawal Syndrome, also called NOWS. Babies with NOWS often have tremors, a hard time sleeping, excessive crying, and trouble feeding. Some babies that have NOWS need medicine. Doctors have two ways of providing medicine that are widely used today:

1. 1.Scheduled opioid taper approach. The baby gets medicine at regular times. As symptoms get better, the amount of medicine the baby gets decreases until the baby no longer needs medicine. This is called a medicine taper.
2. 2.Symptom-based approach. The baby will only get medicine when they show signs of NOWS, instead of at regular times. If the baby is showing no signs of NOWS, no medicine will be given.

Conditions

Neonatal Opiate Withdrawal Syndrome

Keywords

NOWS

Outcome Measures

Primary Outcomes (1)

• Time from birth until medically ready for discharge

  Time from birth until infant meets criteria for medically ready for discharge (days). An infant is considered medically ready for discharge when they are discharged by the medical provider or when they meet the following criteria the following criteria: * ≥ 96 hours of age * ≥ 48 hours since last dose of opioid treatment (i.e., morphine, methadone, or buprenorphine)

  From date of birth until hospital discharge or 1 year, whichever comes first.

Secondary Outcomes (8)

• Receipt of pharmacologic treatment

  From date of birth until hospital discharge or 1 year, whichever comes first.

• Length of hospital stay

  From date of birth until hospital discharge or 1 year, whichever comes first.

• Safety outcomes

  From date of birth until 3 months of life

• Total number opioid doses

  From date of birth until hospital discharge or 1 year, whichever comes first.

• Receipt of secondary medications

  From date of birth until hospital discharge or 1 year, whichever comes first.

Study Arms (2)

Sequence 1

OTHER

This sequence will assign eligible participants to a three-week run-in period followed by a scheduled opioid taper approach for five months followed by a three-week washout period followed by symptom-based dosing approach for five months.

Other: Symptom-based Dosing Approach; Other: Scheduled Opioid Taper Approach

Sequence 2

OTHER

This sequence will assign eligible participants to a three-week run-in period followed by a symptom-based dosing approach for five months followed by a three-week washout period followed by scheduled opioid taper approach for five months.

Other: Symptom-based Dosing Approach; Other: Scheduled Opioid Taper Approach

Interventions

Symptom-based Dosing Approach OTHER

During this approach to care, all enrolled infants with NOWS at the study site will be treated with the symptom-based dosing approach if they meet the withdrawal threshold for pharmacologic treatment. Participants may receive up to 3 doses of the study site's preferred opioid during a 24-hour period to treat signs of withdrawal once the threshold for pharmacologic intervention is met. If a 4th dose is required within a 24-hour period, the study site will transition to the scheduled opioid taper algorithm used at the study site to complete the infant's pharmacologic treatment.

Sequence 1; Sequence 2

Scheduled Opioid Taper Approach OTHER

During this approach to care, all enrolled infants with NOWS at the study site will be treated with the study site's usual scheduled opioid taper approach, as detailed in each site's treatment algorithm, if they meet the withdrawal threshold for pharmacologic treatment.

Sequence 1; Sequence 2

Eligibility Criteria

• Age: 1 Hour - 48 Hours
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• The infant is greater than or equal to 36 weeks gestation.
• The infant had antenatal opioid exposure identified by at least one of the following:
• History of maternal opioid use during pregnancy;
• Positive maternal toxicology screen for opioids during the second or third trimester of pregnancy; and/or
• Positive infant toxicology screen for opioids during the initial hospital stay.
• The infant is being assessed and managed for NOWS at an eligible study site.
• The infant is at risk for pharmacologic treatment for NOWS defined by either of the following
• At least 1 score ≥ 8 if assessed and managed with FNAST or modification thereof
• At least 1 "yes" if assessed and managed with the ESC care approach

You may not qualify if:

• The infant has major birth defect(s).
• The infant has neonatal encephalopathy (inclusive of hypoxic ischemic encephalopathy), a metabolic disorder, stroke, intracranial hemorrhage, or meningitis diagnosed prior to the initiation of pharmacologic treatment.
• The infant is receiving respiratory support (any positive pressure or oxygen therapy) at 48 hours of age.
• The infant has undergone major surgical intervention prior to or at 48 hours of age.
• The infant has postnatal opioid exposure prior to the initiation of treatment for NOWS.
• The infant was outborn and pharmacologic treatment was initiated at the transferring hospital.
• The infant is assessed for eligibility during the study site's three-week washout period.

Sponsors & Collaborators

• HELP for NOWS Consortium: lead
• National Institutes of Health (NIH): collaborator
• Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD): collaborator

Study Sites (23)

University of Alabama at Birmingham

Birmingham, Alabama, 35294, United States

Location

University of Arkansas for Medical Sciences

Little Rock, Arkansas, 72205, United States

Location

ChristianaCare

Wilmington, Delaware, 19801, United States

Location

University of South Florida Health

Tampa, Florida, 33606, United States

Location

Sidney & Lois Eskenazi Hospital

Indianapolis, Indiana, 46202, United States

Location

University of Louisville Hospital

Jeffersonville, Indiana, 47130, United States

Location

University of Kansas Hospital

Kansas City, Kansas, 66160, United States

Location

St. Elizabeth Healthcare

Edgewood, Kentucky, 41017, United States

Location

Kentucky Children's Hospital

Lexington, Kentucky, 40536, United States

Location

Norton Children's Hospital

Louisville, Kentucky, 40202, United States

Location

Norton Women's and Children's Hospital

Louisville, Kentucky, 40207, United States

Location

University of Nebraska Medical Center

Omaha, Nebraska, 68198, United States

Location

AtlantiCare Regional Medical Center

Atlantic City, New Jersey, 08401, United States

Location

University of New Mexico Health Sciences Center

Albuquerque, New Mexico, 87131, United States

Location

University of Rochester Medical Center

Rochester, New York, 14642, United States

Location

Good Samaritan Hospital

Cincinnati, Ohio, 45202, United States

Location

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, 45229, United States

Location

Kettering Health Main Campus

Kettering, Ohio, 45429, United States

Location

Oklahoma Children's Hospital OU Health

Oklahoma City, Oklahoma, 73104, United States

Location

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, 19104, United States

Location

Pennsylvania Hospital

Philadelphia, Pennsylvania, 19107, United States

Location

Thomas Jefferson University Hospital

Philadelphia, Pennsylvania, 19107, United States

Location

University of Utah Health

Salt Lake City, Utah, 84158, United States

Location

Related Publications (1)

• Young LW, Babineau DC, Das A, DeMauro S, Kraft WK, Lorch S, Walsh MC, Merhar S, Devlin LA; Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research and the National Institutes of Health (NIH) Helping to End Addiction Long-term (HEAL) Initiative. Optimizing pharmacologic treatment for neonatal opioid withdrawal syndrome (OPTimize NOW): a symptom-based dosing approach study protocol for a multi-center, cluster crossover design randomized controlled trial. Trials. 2025 Aug 27;26(1):317. doi: 10.1186/s13063-025-09035-x.

  PMID: 40866977 DERIVED

Related Links

• Related Info

Study Officials

• Lori Devlin, MD

  University of Louisville

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: NETWORK
• Responsible Party: SPONSOR

Model Details: A two-period cluster crossover design will be used in this study. Study sites will be randomized in a 1:1 allocation ratio to one of two sequences: 1. A three-week run-in period followed by a scheduled opioid taper approach for five months followed by a three-week washout period followed by a symptom-based dosing approach for five months. 2. A three-week run-in period followed by a symptom-based dosing approach for five months followed by a three-week washout period followed by a scheduled opioid taper approach for five months.

Study Record Dates

• First Submitted: July 27, 2023
• First Posted: August 7, 2023
• Study Start: March 25, 2024
• Primary Completion: May 27, 2025
• Study Completion: July 15, 2025
• Last Updated: February 27, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Time Frame: Within 1 year of study completion.

Locations

US (23)