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

HELP for NOWS Consortium

Status: Not yet enrolling

Conditions: Neonatal Opioid Withdrawal Syndrome

Study type: Observational

Funder types: NETWORK; NIH

Identifiers

NCT07278375

HELP for NOWS 03

1UG1HD107628 (U.S. NIH Grant/Contract)

1UG1HD107653 (U.S. NIH Grant/Contract)

1UG1HD107580 (U.S. NIH Grant/Contract)

1U24HD107621 (U.S. NIH Grant/Contract)

1UG1HD107650 (U.S. NIH Grant/Contract)

1UG1HD107616 (U.S. NIH Grant/Contract)

1UG1HD107631 (U.S. NIH Grant/Contract)

1UG1HD107649 (U.S. NIH Grant/Contract)

1UG1HD107627 (U.S. NIH Grant/Contract)

Details and patient eligibility

About

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.

Full 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.

Enrollment: 796 estimated patients

Sex: All

Volunteers: No Healthy Volunteers

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.

Trial design

796 participants in 2 patient groups

Infants treated with buprenorphine

Description:

Infants treated with buprenorphine as the primary opioid for NOWS

Infants treated with morphine

Description:

Infants treated with morphine as the primary opioid for NOWS