Target Trial Emulation for Pharmacologic Treatment of Neonatal Opioid Withdrawal Syndrome (TreaT NOW)

February 24, 2026 updated by: HELP for NOWS Consortium

The goal of this observational study is to learn how two medicines used in routine care-buprenorphine and morphine-affect recovery in newborns (≥36 weeks' gestation) with Neonatal Opioid Withdrawal Syndrome (NOWS). The main questions it aims to answer are:

  1. Do infants treated with buprenorphine become medically ready for discharge sooner than those treated with morphine?
  2. Does one treatment lead to better overall clinical outcomes than the other?

Researchers will compare infants who received buprenorphine with infants who received morphine to see whether one treatment helps babies recover more quickly.

Participants will not be asked to do anything. Instead, the study team will collect information already documented in the infant's and mother's medical records securely without any contact or changes to clinical care.

No new medicines, procedures, or visits are involved. This study only reviews existing clinical data to better understand which commonly used treatment may support faster recovery for newborns with NOWS.

Study Overview

Status

Recruiting

Conditions

Detailed Description

Neonatal Opioid Withdrawal Syndrome (NOWS) occurs in infants who were exposed to opioids during pregnancy and may lead to symptoms such as irritability, feeding difficulties, and trouble sleeping. Many hospitals treat these symptoms with either morphine or buprenorphine, but it is not yet known whether one medication helps infants recover more quickly. This study aims to answer that question by reviewing information already documented in medical records from hospitals that routinely use one of these treatments.

The study will include approximately 796 infants, all born at 36 weeks' of gestation or later and treated for NOWS with either buprenorphine or morphine as part of usual clinical care. Data will be collected from about 22 hospitals across the United States. Researchers will review existing medical record information such as the infant's birth characteristics, withdrawal symptoms, details of treatment (including medication choice and dosing approach), feeding practices, non-pharmacologic care, and clinical outcomes-including the key measure of how long it took for the infant to become medically ready for discharge.

Because treatment decisions are made by the clinical team and not assigned by the study, researchers will use advanced statistical methods to compare outcomes between infants who received buprenorphine and those who received morphine. These methods allow the team to adjust for differences between infants and hospitals, helping ensure that comparisons are as fair and accurate as possible. The goal is to estimate how outcomes would differ if all infants received one medication versus the other in real-world practice.

No infants or parents will be contacted for this study, and no additional treatments, tests, or procedures will be performed. All data come from routine clinical care. The regulatory review for this project determined that informed consent from families is not required because the study uses only existing medical information and does not involve any interaction with participants or changes to medical care. All collected data will be handled securely and in compliance with federal privacy requirements.

The information learned from this research may help improve care for future infants with NOWS by providing clearer evidence on how commonly used treatments compare in supporting recovery.

Study Type

Observational

Enrollment (Estimated)

796

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • United States
    • Alabama
      • Birmingham, Alabama, United States, 35294
        • Recruiting
        • University of Alabama at Birmingham
        • Contact:
          • Namasivayam Ambalavanan, MD
        • Principal Investigator:
          • Namasivayam Ambalavanan, MD
    • Arkansas
      • Little Rock, Arkansas, United States, 72205-7199
        • Recruiting
        • University of Arkansas for Medical Sciences
        • Contact:
        • Principal Investigator:
          • Richard W Hall, MD
    • Delaware
      • Wilmington, Delaware, United States, 19801
        • Not yet recruiting
        • ChristianaCare
        • Contact:
        • Principal Investigator:
          • Kelley Z Kovatis, MD
    • Florida
      • Tampa, Florida, United States, 33606
        • Recruiting
        • University of South Florida Health
        • Contact:
        • Principal Investigator:
          • Tanner Wright, MD, FAAP
    • Indiana
      • Indianapolis, Indiana, United States, 46202
        • Recruiting
        • Sidney & Lois Eskenazi Hospital
        • Principal Investigator:
          • Gregory Sokol, MD
        • Contact:
          • Gregory Sokol, MD
          • Phone Number: 317-274-8021
          • Email: gsokol@iu.edu
      • Indianapolis, Indiana, United States, 46202-5119
        • Recruiting
        • Riley Hospital for Children at IU Health
        • Principal Investigator:
          • Gregory Sokol, MD
        • Contact:
          • Gregory Sokol, MD
          • Phone Number: 317-274-8021
          • Email: gsokol@iu.edu
      • Jeffersonville, Indiana, United States, 47130
        • Not yet recruiting
        • University of Louisville Hospital
        • Principal Investigator:
          • Lori Devlin, DO, MHA, MS
        • Contact:
    • Kentucky
      • Edgewood, Kentucky, United States, 41017
        • Not yet recruiting
        • St. Elizabeth Healthcare
        • Principal Investigator:
          • Stephanie Merhar, MD, MS
        • Contact:
      • Lexington, Kentucky, United States, 40536
        • Recruiting
        • Kentucky Children's Hospital
        • Contact:
          • Thitinart Sithisarn, MD, PhD
          • Phone Number: 859-257-6481
          • Email: tsith2@uky.edu
        • Principal Investigator:
          • Thitinart Sithisarn, MD, PhD, FAAP
      • Louisville, Kentucky, United States, 40202
        • Not yet recruiting
        • Norton Children's Hospital
        • Principal Investigator:
          • Lori Devlin, DO, MHA, MS
        • Contact:
      • Louisville, Kentucky, United States, 40207
        • Not yet recruiting
        • Norton Women's and Children's Hospital
        • Principal Investigator:
          • Lori Devlin, DO, MHA, MS
        • Contact:
    • New Jersey
      • Camden, New Jersey, United States, 08103
        • Not yet recruiting
        • Children's Regional Hospital, Cooper University Health Care
        • Contact:
        • Principal Investigator:
          • Alla Kushnir, MD, FAAP
    • New Mexico
      • Albuquerque, New Mexico, United States, 87131
        • Recruiting
        • University of New Mexico Health Sciences Center
        • Contact:
        • Principal Investigator:
          • Lawrence M Leeman, MD, MPH
    • New York
      • Rochester, New York, United States, 14642
        • Not yet recruiting
        • University of Rochester Medical Center
        • Contact:
        • Principal Investigator:
          • Joseph Bliss, MD, PhD
    • Ohio
      • Cincinnati, Ohio, United States, 45229
        • Not yet recruiting
        • Cincinnati Children's Hospital Medical Center
        • Principal Investigator:
          • Stephanie Merhar, MD, MS
        • Contact:
      • Cincinnati, Ohio, United States, 45202
        • Not yet recruiting
        • Good Samaritan Hospital
        • Principal Investigator:
          • Stephanie Merhar, MD, MS
        • Contact:
      • Cleveland, Ohio, United States, 44106
        • Not yet recruiting
        • Rainbow Babies and Children's Hospital
        • Contact:
        • Principal Investigator:
          • Moira Crowley, MD
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19104
        • Recruiting
        • Children's Hospital of Philadelphia
        • Principal Investigator:
          • Scott Lorch, MD, MSCE
        • Contact:
          • Scott Lorch, MD, MSCE
          • Phone Number: 215-590-1653
          • Email: LORCH@chop.edu
      • Philadelphia, Pennsylvania, United States, 19107
        • Recruiting
        • Thomas Jefferson University Hospital
        • Contact:
        • Principal Investigator:
          • Walter K Kraft, MD
      • Philadelphia, Pennsylvania, United States, 19107
        • Not yet recruiting
        • Pennsylvania Hospital
        • Contact:
        • Principal Investigator:
          • Karen Puopolo, MD, PhD
    • Utah
      • Salt Lake City, Utah, United States, 84158
        • Not yet recruiting
        • University of Utah Health
        • Principal Investigator:
          • Bhanu Muniyappa, MD
        • Contact:
    • Vermont
      • Burlington, Vermont, United States, 05401
        • Not yet recruiting
        • University of Vermont Medical Center
        • Contact:
        • Principal Investigator:
          • Adrienne Pahl, MD

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Child
  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Sampling Method

Non-Probability Sample

Study Population

The study population will include infant and mother dyads who fulfill the study inclusion and exclusion criteria.

Description

Inclusion Criteria:

  1. Infant is ≥ 36 weeks' gestational age

  2. Infant had antenatal opioid exposure identified by at least one of the following:

    1. History of maternal opioid use during the second and/or third trimester of pregnancy as noted in the mother's or infant's medical record;
    2. Positive maternal toxicology screen for opioids during the second or third trimester of pregnancy; and/or
    3. 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 the Finnegan Neonatal Abstinence Scoring Tool (FNAST) or modification thereof
    • At least 1 "yes" if assessed and managed with the Eat, Sleep, Console (ESC) care approach
  5. Infant met all inclusion criteria on or after March 25, 2024.

Exclusion Criteria:

  1. Infant has major congenital anomalies.
  2. 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. Infant is receiving respiratory support (any positive pressure or oxygen therapy) at 48 hours of age.
  4. Infant has undergone major surgical intervention prior to or at 48 hours of age.
  5. Infant has postnatal opioid exposure prior to the initiation of pharmacologic treatment for NOWS.
  6. Infant was outborn and pharmacologic treatment was initiated at the transferring hospital.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Cohorts and Interventions

Group / Cohort
Infants treated with buprenorphine
Infants treated with buprenorphine as the primary opioid for NOWS
Infants treated with morphine
Infants treated with morphine as the primary opioid for NOWS

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Time from birth until infant meets criteria for medically ready for discharge (count)
Time Frame: From date of birth until date of infant meeting criteria for medically ready for discharge (estimated to be < 90 days).

Number of days from birth until infant meets criteria for medically ready for discharge. An infant is considered medically ready for discharge when they are discharged by the medical provider or when they meet both of the following criteria:

  • 96 hours of age
  • 48 hours since last dose of treatment with morphine or buprenorphine
From date of birth until date of infant meeting criteria for medically ready for discharge (estimated to be < 90 days).

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Length of hospital stay (count)
Time Frame: From date of birth until date of hospital discharge (estimated to be < 90 days).
Number of days between birth and hospital discharge
From date of birth until date of hospital discharge (estimated to be < 90 days).
Length of primary opioid treatment (count)
Time Frame: From date of birth until date of last primary opioid dose administration (estimated to be < 90 days).
Number of days between the first and the last primary opioid dose administered
From date of birth until date of last primary opioid dose administration (estimated to be < 90 days).
Number of primary opioid doses administered (count)
Time Frame: From date of birth until date of last primary opioid dose administration (estimated to be < 90 days).
Number of primary opioid doses administered (count)
From date of birth until date of last primary opioid dose administration (estimated to be < 90 days).
Receipt of secondary medication (binary)
Time Frame: From date of birth until date of first non-opioid secondary medication administration or until date of hospital discharge, whichever comes first (estimated to be < 90 days).
Receipt of at least one dose of any amount of phenobarbital, clonidine, or some other non-opioid medication as a secondary medication
From date of birth until date of first non-opioid secondary medication administration or until date of hospital discharge, whichever comes first (estimated to be < 90 days).
Inpatient composite safety outcome (binary)
Time Frame: From date of birth until date of first occurrence of seizure or excessive weight loss more than 15% from birthweight or until date of last primary opioid dose administration, whichever comes first (estimated to be < 90 days).

Occurrence of at least one of the following events between birth and the last primary opioid dose administered:

  • Seizures
  • Excessive weight loss more than 15% from birthweight
From date of birth until date of first occurrence of seizure or excessive weight loss more than 15% from birthweight or until date of last primary opioid dose administration, whichever comes first (estimated to be < 90 days).
Inpatient composite critical safety outcome (binary)
Time Frame: From date of birth until date of first occurrence of non-accidental trauma or death or until date of last primary opioid dose administration, whichever comes first (estimated to be < 90 days).

Occurrence of at least one of the following events between birth and the last primary opioid dose administered:

  • Non-accidental trauma
  • Death
From date of birth until date of first occurrence of non-accidental trauma or death or until date of last primary opioid dose administration, whichever comes first (estimated to be < 90 days).
Inpatient composite safety outcome after receipt of pharmacologic treatment (binary)
Time Frame: From date of first primary opioid dose administration until date of first occurrence of seizure or excessive weight loss more than 15% from birthweight or until date of hospital discharge, whichever comes first (estimated to be < 90 days).

Occurrence of at least one of the following events between first primary opioid dose administered and the data of hospital discharge:

  • Seizures
  • Excessive weight loss more than 15% from birthweight
From date of first primary opioid dose administration until date of first occurrence of seizure or excessive weight loss more than 15% from birthweight or until date of hospital discharge, whichever comes first (estimated to be < 90 days).
Inpatient composite critical safety outcome after receipt of pharmacologic treatment (binary)
Time Frame: From date of first primary opioid dose administration until date of first occurrence of non-accidental trauma or death or until date of hospital discharge, whichever comes first (estimated to be < 90 days).

Occurrence of at least one of the following events between first primary opioid dose administered and hospital discharge:

  • Non-accidental trauma
  • Death
From date of first primary opioid dose administration until date of first occurrence of non-accidental trauma or death or until date of hospital discharge, whichever comes first (estimated to be < 90 days).

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

HELP for NOWS Consortium

Collaborators

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

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

December 9, 2025

Primary Completion (Estimated)

June 19, 2026

Study Completion (Estimated)

August 30, 2026

Study Registration Dates

First Submitted

November 21, 2025

First Submitted That Met QC Criteria

December 1, 2025

First Posted (Actual)

December 12, 2025

Study Record Updates

Last Update Posted (Actual)

February 25, 2026

Last Update Submitted That Met QC Criteria

February 24, 2026

Last Verified

February 1, 2026

More Information

Terms related to this study

Keywords

Other Study ID Numbers

  • HELP for NOWS 03
  • 1U24HD107621 (U.S. NIH Grant/Contract)
  • 1UG1HD107628 (U.S. NIH Grant/Contract)
  • 1UG1HD107580 (U.S. NIH Grant/Contract)
  • 1UG1HD107649 (U.S. NIH Grant/Contract)
  • 1UG1HD107650 (U.S. NIH Grant/Contract)
  • 1UG1HD107653 (U.S. NIH Grant/Contract)
  • 1UG1HD107627 (U.S. NIH Grant/Contract)
  • 1UG1HD107631 (U.S. NIH Grant/Contract)
  • 1UG1HD107616 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

Data collected for this study will be analyzed and stored at the DCC, RTI International. NIH Helping to End Addiction Long-term Initiative (HEAL) and NICHD requirements for data-sharing will apply. NIH has had a long-standing policy to share and make available to the public the results and accomplishments of the activities that it funds. In accordance with these policies (available at HEAL Public Access and Data Sharing | NIH HEAL Initiative), we will share de-identified data collected for the study. After the study is completed, the de-identified, archived data will be transmitted to a NIH HEAL supported repository, for use by other researchers including those outside of the study.

IPD Sharing Time Frame

Within 1 year of study completion.

IPD Sharing Supporting Information Type

  • STUDY_PROTOCOL
  • SAP

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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