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

NCT ID: NCT05980260

Last Updated: 2025-07-02

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

ACTIVE_NOT_RECRUITING

Clinical Phase

PHASE3

Total Enrollment

480 participants

Study Classification

INTERVENTIONAL

Study Start Date

2024-03-25

Study Completion Date

2025-08-27

Brief Summary

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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. 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. 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.

We are doing the OPTimize NOW study to figure out the best way to give medicine to babies with NOWS.

Detailed Description

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This two-period cluster crossover clinical trial will compare the length of time from birth until medically ready for discharge between infants with neonatal opioid withdrawal syndrome (NOWS) who are ≥ 36 weeks' gestation, at risk for pharmacologic treatment, and treated for NOWS with either a symptom-based dosing approach or a scheduled opioid taper approach.

Each study site (i.e., cluster) will be randomized in a 1:1 allocation ratio to one of two sequences:

* A three-week run-in period followed by a scheduled opioid taper approach for five months (Period 1) followed by a three-week washout period followed by a symptom-based dosing approach for five months (Period 2)
* A three-week run-in period followed by a symptom-based dosing approach for five months (Period 1) followed by a three-week washout period followed by scheduled opioid taper approach for five months (Period 2)

The randomization scheme will be stratified by the assessment and management approach used at each study site (i.e., Finnegan or Eat, Seep and Console).

Conditions

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Neonatal Opiate Withdrawal Syndrome

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

CROSSOVER

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.
Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Sequence 1

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.

Group Type OTHER

Symptom-based Dosing Approach

Intervention Type 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.

Scheduled Opioid Taper Approach

Intervention Type 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 2

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.

Group Type OTHER

Symptom-based Dosing Approach

Intervention Type 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.

Scheduled Opioid Taper Approach

Intervention Type 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.

Interventions

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Symptom-based Dosing Approach

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.

Intervention Type OTHER

Scheduled Opioid Taper Approach

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.

Intervention Type OTHER

Eligibility Criteria

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Inclusion Criteria

1. The infant is greater than or equal to 36 weeks gestation.
2. 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.
3. The infant is being assessed and managed for NOWS at an eligible study site.
4. 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

Exclusion Criteria

1. The infant has major birth defect(s).
2. 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.
3. The infant is receiving respiratory support (any positive pressure or oxygen therapy) at 48 hours of age.
4. The infant has undergone major surgical intervention prior to or at 48 hours of age.
5. The infant has postnatal opioid exposure prior to the initiation of treatment for NOWS.
6. The infant was outborn and pharmacologic treatment was initiated at the transferring hospital.
7. The infant is assessed for eligibility during the study site's three-week washout period.
Minimum Eligible Age

1 Hour

Maximum Eligible Age

48 Hours

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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National Institutes of Health (NIH)

NIH

Sponsor Role collaborator

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

NIH

Sponsor Role collaborator

HELP for NOWS Consortium

NETWORK

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Lori Devlin, MD

Role: PRINCIPAL_INVESTIGATOR

University of Louisville

Locations

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University of Alabama at Birmingham

Birmingham, Alabama, United States

Site Status

University of Arkansas for Medical Sciences

Little Rock, Arkansas, United States

Site Status

ChristianaCare

Wilmington, Delaware, United States

Site Status

University of South Florida Health

Tampa, Florida, United States

Site Status

Sidney & Lois Eskenazi Hospital

Indianapolis, Indiana, United States

Site Status

University of Louisville Hospital

Jeffersonville, Indiana, United States

Site Status

University of Kansas Hospital

Kansas City, Kansas, United States

Site Status

St. Elizabeth Healthcare

Edgewood, Kentucky, United States

Site Status

Kentucky Children's Hospital

Lexington, Kentucky, United States

Site Status

Norton Children's Hospital

Louisville, Kentucky, United States

Site Status

Norton Women's and Children's Hospital

Louisville, Kentucky, United States

Site Status

University of Nebraska Medical Center

Omaha, Nebraska, United States

Site Status

AtlantiCare Regional Medical Center

Atlantic City, New Jersey, United States

Site Status

University of New Mexico Health Sciences Center

Albuquerque, New Mexico, United States

Site Status

University of Rochester Medical Center

Rochester, New York, United States

Site Status

Good Samaritan Hospital

Cincinnati, Ohio, United States

Site Status

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, United States

Site Status

Kettering Health Main Campus

Kettering, Ohio, United States

Site Status

Oklahoma Children's Hospital OU Health

Oklahoma City, Oklahoma, United States

Site Status

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, United States

Site Status

Pennsylvania Hospital

Philadelphia, Pennsylvania, United States

Site Status

Thomas Jefferson University Hospital

Philadelphia, Pennsylvania, United States

Site Status

University of Utah Health

Salt Lake City, Utah, United States

Site Status

Countries

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United States

References

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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.

Reference Type DERIVED
PMID: 40866977 (View on PubMed)

Related Links

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Other Identifiers

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1U24HD107621

Identifier Type: NIH

Identifier Source: secondary_id

View Link

1UG1HD107628

Identifier Type: NIH

Identifier Source: secondary_id

View Link

1UG1HD107580

Identifier Type: NIH

Identifier Source: secondary_id

View Link

1UG1HD107649

Identifier Type: NIH

Identifier Source: secondary_id

View Link

1UG1HD107650

Identifier Type: NIH

Identifier Source: secondary_id

View Link

1UG1HD107653

Identifier Type: NIH

Identifier Source: secondary_id

View Link

1UG1HD107627

Identifier Type: NIH

Identifier Source: secondary_id

View Link

1UG1HD107631

Identifier Type: NIH

Identifier Source: secondary_id

View Link

1UG1HD107616

Identifier Type: NIH

Identifier Source: secondary_id

View Link

HELP for NOWS 02

Identifier Type: -

Identifier Source: org_study_id

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