Neonatal Opiate Withdrawal SyndromePhase 3OPTimize NOWNCT05980260

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

A Phase 3 study testing Symptom-based Dosing Approach and Scheduled Opioid Taper Approach in people with Neonatal Opiate Withdrawal Syndrome, run by HELP for NOWS Consortium at 23 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial 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. Read more about this study

Who is it for?: Ages 1 hour to 48 hours
Conditions the study is for: Neonatal Opiate Withdrawal Syndrome
What is being tested?: Symptom-based Dosing Approach and Scheduled Opioid Taper Approach
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 626 participants
Where: 23 sitesUnited States
Study dates: 25 Mar 2024to 15 Jul 2025
Phase: Phase 3
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 1 hour to 48 hours
All sexes
No healthy volunteers
Child

Who may be able to join

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.

Show all 9Show fewer

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

Who cannot join

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.

Trial locations and contacts

23 sites in 1 country.

City, postcode or hospital

23 sites in 1 country

United States23 sites

University of New Mexico Health Sciences Center
Albuquerque, New Mexico, 87131
AtlantiCare Regional Medical Center
Atlantic City, New Jersey, 08401
University of Alabama at Birmingham
Birmingham, Alabama, 35294
Good Samaritan Hospital
Cincinnati, Ohio, 45202
Cincinnati Children's Hospital Medical Center
Cincinnati, Ohio, 45229
St. Elizabeth Healthcare
Edgewood, Kentucky, 41017
Sidney & Lois Eskenazi Hospital
Indianapolis, Indiana, 46202
University of Louisville Hospital
Jeffersonville, Indiana, 47130
University of Kansas Hospital
Kansas City, Kansas, 66160
Kettering Health Main Campus
Kettering, Ohio, 45429
Kentucky Children's Hospital
Lexington, Kentucky, 40536
University of Arkansas for Medical Sciences
Little Rock, Arkansas, 72205
Norton Children's Hospital
Louisville, Kentucky, 40202
Norton Women's and Children's Hospital
Louisville, Kentucky, 40207
Oklahoma Children's Hospital OU Health
Oklahoma City, Oklahoma, 73104
University of Nebraska Medical Center
Omaha, Nebraska, 68198
Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, 19104
Pennsylvania Hospital
Philadelphia, Pennsylvania, 19107
Thomas Jefferson University Hospital
Philadelphia, Pennsylvania, 19107
University of Rochester Medical Center
Rochester, New York, 14642
University of Utah Health
Salt Lake City, Utah, 84158
University of South Florida Health
Tampa, Florida, 33606
ChristianaCare
Wilmington, Delaware, 19801

Other trials in United States

About this study

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.
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.

Read the detailed description

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: Neonatal Opiate Withdrawal Syndrome
Being tested: Symptom-based Dosing Approach, Scheduled Opioid Taper Approach
Keywords: NOWS

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Symptom-based Dosing ApproachOther
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 ApproachOther
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.

Study groups in NCT05980260
Study group	Role	What they receive
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. Receives: 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. Receives: Other: Symptom-based Dosing Approach; Other: Scheduled Opioid Taper Approach

What is being measured

The primary outcome is the main question the study is designed to answer.

Time From Birth Until Medically Ready for Discharge (ESC Cohort Only)
Time from birth until infant meets criteria for medically ready for discharge (days). For infants that are not pharmacologically treated, they are considered medically ready for discharge at the actual time of discharge. For infants that are pharmacologically treated, they are considered medically ready for discharge when they are both ≥ 96 hours of age and it has been ≥ 48 hours since their last dose of primary opioid treatment (i.e., morphine, methadone, or buprenorphine). If a pharmacologically treated infant has been discharged by the medical provider before meeting both of those criteria, they are considered medically ready for discharge at the actual time of discharge.
This primary outcome is for infants assessed and managed using ESC.
Measured: Measured from infant's time of birth to the time of infant's discharge or transfer from the study hospital

Secondary outcomes (29)

Time From Birth Until Medically Ready for Discharge (Finnegan Cohort Only)
Time from birth until infant meets criteria for medically ready for discharge in days. For infants that are not pharmacologically treated, they are considered medically ready for discharge at the actual time of discharge. For infants that are pharmacologically treated, they are considered medically ready for discharge when they are both ≥ 96 hours of age and it has been ≥ 48 hours since their last dose of primary opioid treatment (i.e., morphine, methadone, or buprenorphine). If a pharmacologically treated infant has been discharged by the medical provider before meeting both of those criteria, they are considered medically ready for discharge at the actual time of discharge.
This secondary outcome is for infants assessed and managed using Finnegan.
Measured: Measured from infant's time of birth to the time of infant's discharge or transfer from the study hospital
Receipt of Pharmacologic Treatment for NOWS (ESC Cohort)
Proportion of infants that ever needed to initiate pharmacologic treatment with an opioid for NOWS therapy prior to hospital discharge or transfer.
This secondary outcome is for infants assessed and managed using ESC.
Measured: Measured from infant's time of birth to the time of infant's discharge or transfer from the study hospital
Length of Hospital Stay (ESC Cohort)
Time from birth until infant is actually discharged (days). For all infants, regardless of pharmacologic treatment, the number of days spent in hospital from birth until discharge is measured. There is no additional criteria or timepoint assessed for this outcome outside of final hospital discharge date.
This secondary outcome is for infants assessed and managed using ESC.
Measured: Measured from infant's time of birth to the time of infant's discharge or transfer from the study hospital
Total Number Primary Opioid Doses (ESC Cohort)
The total number of primary opioid doses administered to pharmacologically treated infants during NOWS therapy.
This secondary outcome is for infants assessed and managed using ESC.
Measured: Measured from infant's time of birth to the time of infant's discharge or transfer from the study hospital
Receipt of Secondary Medications for NOWS (ESC Cohort)
Proportion of pharmacologically treated infants that ever needed to initiate a secondary medication treatment for NOWS therapy prior to hospital discharge or transfer.
This secondary outcome is for infants assessed and managed using ESC.
Measured: Measured from infant's time of birth to the time of infant's discharge or transfer from the study hospital
Transition From Treatment With a Symptom-based Dosing Approach to a Scheduled Opioid Taper Approach Due to Persistent Signs of Withdrawal (ESC Cohort)
The total number of pharmacologically treated infants who transitioned from a symptom-based dosing approach to a scheduled opioid taper approach due to persistent signs of withdrawal prior to hospital discharge or transfer. This outcome is assessed only in infants who initially received a symptom-based dosing approach.
This secondary outcome is for infants assessed and managed using ESC.
Measured: Measured from infant's time of birth to the time of infant's discharge or transfer from the study hospital
Stopped Scheduled Opioid Taper Treatment Due to Excessive Sedation or Respiratory Distress (ESC Cohort)
The total number of pharmacologically treated infants who needed to stop scheduled taper treatment due to excessive sedation or respiratory depression prior to hospital discharge or transfer. This outcome is assessed only in infants who initially received a scheduled taper dosing approach.
This secondary outcome is for infants assessed and managed using ESC.
Measured: Measured from infant's time of birth to the time of infant's discharge or transfer from the study hospital
Receipt of Pharmacologic Treatment for NOWS (Finnegan Cohort)
Proportion of infants that ever needed to initiate pharmacologic treatment with an opioid for NOWS therapy prior to hospital discharge or transfer.
This secondary outcome is for infants assessed and managed using FNAST.
Measured: Measured from infant's time of birth to the time of infant's discharge or transfer from the study hospital
Length of Hospital Stay (Finnegan Cohort)
Time from birth until infant is actually discharged (days). For all infants, regardless of pharmacologic treatment, the number of days spent in hospital from birth until discharge is measured. There is no additional criteria or timepoint assessed for this outcome outside of final hospital discharge date.
This secondary outcome is for infants assessed and managed using FNAST.
Measured: Measured from infant's time of birth to the time of infant's discharge or transfer from the study hospital
Total Number Primary Opioid Doses (Finnegan Cohort)
The total number of primary opioid doses administered to pharmacologically treated infants during NOWS therapy.
This secondary outcome is for infants assessed and managed using FNAST.
Measured: Measured from infant's time of birth to the time of infant's discharge or transfer from the study hospital
Receipt of Secondary Medications for NOWS (Finnegan Cohort)
Proportion of pharmacologically treated infants that ever needed to initiate a secondary medication treatment for NOWS therapy prior to hospital discharge or transfer.
This secondary outcome is for infants assessed and managed using FNAST.
Measured: Measured from infant's time of birth to the time of infant's discharge or transfer from the study hospital
Transition From Treatment With a Symptom-based Dosing Approach to a Scheduled Opioid Taper Approach Due to Persistent Signs of Withdrawal (Finnegan Cohort)
The total number of pharmacologically treated infants who transitioned from a symptom-based dosing approach to a scheduled opioid taper approach due to persistent signs of withdrawal prior to hospital discharge or transfer. This outcome is assessed only in infants who initially received a symptom-based dosing approach.
This secondary outcome is for infants assessed and managed using FNAST.
Measured: Measured from infant's time of birth to the time of infant's discharge or transfer from the study hospital
Stopped Scheduled Opioid Taper Treatment Due to Excessive Sedation or Respiratory Distress (Finnegan Cohort)
The total number of pharmacologically treated infants who needed to stop scheduled taper treatment due to excessive sedation or respiratory depression prior to hospital discharge or transfer. This outcome is assessed only in infants who initially received a scheduled taper dosing approach.
This secondary outcome is for infants assessed and managed using FNAST.
Measured: Measured from infant's time of birth to the time of infant's discharge or transfer from the study hospital
Inpatient Composite Safety Outcome for Infants at Risk for Pharmacologic Treatment, Managed With ESC (Present/Absent)
Proportion of infants that ever experienced a composite safety outcome prior to hospital discharge or transfer, defined as seizures or excessive weight loss >15% from birthweight.
This secondary outcome is for infants assessed and managed using ESC.
Measured: Measured from infant's time of birth to the time of infant's discharge or transfer from the study hospital
Inpatient Composite Safety Outcome for Infants at Risk for Pharmacologic Treatment, Managed With Finnegan (Present/Absent)
Proportion of infants that ever experienced a composite safety outcome prior to hospital discharge or transfer, defined as seizures or excessive weight loss >15% from birthweight.
This secondary outcome is for infants assessed and managed using FNAST.
Measured: Measured from infant's time of birth to the time of infant's discharge or transfer from the study hospital
Inpatient Composite Critical Safety Outcome for Infants at Risk for Pharmacologic Treatment, Managed With ESC (Present/Absent)
Total number of infants that ever experienced a composite critical safety outcome prior to hospital discharge or transfer, defined as non-accidental trauma or death.
This secondary outcome is for infants assessed and managed using ESC.
Measured: Measured from infant's time of birth to the time of infant's discharge or transfer from the study hospital
Inpatient Composite Critical Safety Outcome for Infants at Risk for Pharmacologic Treatment, Managed With Finnegan (Present/Absent)
Total number of infants that ever experienced a composite critical safety outcome prior to hospital discharge or transfer, defined as non-accidental trauma or death.
This secondary outcome is for infants assessed and managed using FNAST.
Measured: Measured from infant's time of birth to the time of infant's discharge or transfer from the study hospital
Outpatient Composite Safety Outcome at Risk for Pharmacologic Treatment, Managed With ESC (Present/Absent)
Proportion of infants that ever experienced a composite safety outcome between hospital discharge or transfer and 3 months of age, defined as any acute/urgent care visit, any emergency room visit, or any hospital readmission.
This secondary outcome is for infants assessed and managed using ESC.
Measured: Measured from infant's time of discharge or transfer from study hospital to time of follow-up chart review at three months of age
Outpatient Composite Safety Outcome at Risk for Pharmacologic Treatment, Managed With Finnegan (Present/Absent)
Proportion of infants that ever experienced a composite safety outcome between hospital discharge or transfer and 3 months of age, defined as any acute/urgent care visit, any emergency room visit, or any hospital readmission.
This secondary outcome is for infants assessed and managed using FNAST.
Measured: Measured from infant's time of discharge or transfer from study hospital to time of follow-up chart review at three months of age
Outpatient Composite Critical Safety Outcome at Risk for Pharmacologic Treatment, Managed With ESC (Present/Absent)
Total number of infants that ever experienced a critical composite safety outcome between hospital discharge or transfer and 3 months of age, defined as non-accidental trauma or death.
This secondary outcome is for infants assessed and managed using ESC.
Measured: Measured from infant's time of discharge or transfer from study hospital to time of follow-up chart review at three months of age
Outpatient Composite Critical Safety Outcome at Risk for Pharmacologic Treatment, Managed With Finnegan (Present/Absent)
Total number of infants that ever experienced a critical composite safety outcome between hospital discharge or transfer and 3 months of age, defined as non-accidental trauma or death.
This secondary outcome is for infants assessed and managed using FNAST.
Measured: Measured from infant's time of discharge or transfer from study hospital to time of follow-up chart review at three months of age
Inpatient Composite Safety Outcome for Infants Treated Pharmacologically, Managed With ESC (Present/Absent)
Total number of pharmacologically treated infants that ever experienced a composite safety outcome after the initiation of their pharmacologic treatment and prior to hospital discharge or transfer, defined as seizures or excessive weight loss >15% from birthweight.
This secondary outcome is for infants assessed and managed using ESC.
Measured: Measured from time that pharmacologic treatment was initiated to the time of infant's discharge or transfer from the study hospital
Inpatient Composite Safety Outcome for Infants Treated Pharmacologically, Managed With Finnegan (Present/Absent)
Total number of pharmacologically treated infants that ever experienced a composite safety outcome after the initiation of their pharmacologic treatment and prior to hospital discharge or transfer, defined as seizures or excessive weight loss >15% from birthweight.
This secondary outcome is for infants assessed and managed using FNAST.
Measured: Measured from time that pharmacologic treatment was initiated to the time of infant's discharge or transfer from the study hospital
Inpatient Composite Critical Safety Outcome for Infants Treated Pharmacologically, Managed With ESC (Present/Absent)
Total number of pharmacologically treated infants that ever experienced a composite critical safety outcome after the initiation of pharmacologic treatment and prior to hospital discharge or transfer, defined as non-accidental trauma or death.
This secondary outcome is for infants assessed and managed using ESC.
Measured: Measured from time that pharmacologic treatment was initiated to the time of infant's discharge or transfer from the study hospital
Inpatient Composite Critical Safety Outcome for Infants Treated Pharmacologically, Managed With Finnegan (Present/Absent)
Total number of pharmacologically treated infants that ever experienced a composite critical safety outcome after the initiation of pharmacologic treatment and prior to hospital discharge or transfer, defined as non-accidental trauma or death.
This secondary outcome is for infants assessed and managed using FNAST.
Measured: Measured from time that pharmacologic treatment was initiated to the time of infant's discharge or transfer from the study hospital
Outpatient Composite Safety Outcome for Infants Treated Pharmacologically, Managed With ESC (Present/Absent)
Proportion of pharmacologically treated infants that ever experienced a composite safety outcome between hospital discharge or transfer and 3 months of age, defined as any acute/urgent care visit, any emergency room visit, or any hospital readmission.
This secondary outcome is for infants assessed and managed using ESC.
Measured: Measured from infant's time of discharge or transfer from study hospital to time of follow-up chart review at three months of age
Outpatient Composite Safety Outcome for Infants Treated Pharmacologically, Managed With Finnegan (Present/Absent)
Proportion of pharmacologically treated infants that ever experienced a composite safety outcome between hospital discharge or transfer and 3 months of age, defined as any acute/urgent care visit, any emergency room visit, or any hospital readmission.
This secondary outcome is for infants assessed and managed using FNAST.
Measured: Measured from infant's time of discharge or transfer from study hospital to time of follow-up chart review at three months of age
Outpatient Composite Critical Safety Outcome for Infants Treated Pharmacologically, Managed With ESC (Present/Absent)
Total number of pharmacologically treated infants that ever experienced a critical composite safety outcome between hospital discharge or transfer and 3 months of age, defined as non-accidental trauma or death.
This secondary outcome is for infants assessed and managed using ESC.
Measured: Measured from infant's time of discharge or transfer from study hospital to time of follow-up chart review at three months of age
Outpatient Composite Critical Safety Outcome for Infants Treated Pharmacologically, Managed With Finnegan (Present/Absent)
Total number of pharmacologically treated infants that ever experienced a critical composite safety outcome between hospital discharge or transfer and 3 months of age, defined as non-accidental trauma or death.
This secondary outcome is for infants assessed and managed using FNAST.
Measured: Measured from infant's time of discharge or transfer from study hospital to time of follow-up chart review at three months of age

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

25 Mar 202415 Jul 2025

First posted7 Aug 2023
Study start25 Mar 2024
Primary completion27 May 2025
Study completion15 Jul 2025

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (2)Papers the sponsor has linked to this study.
Other trials for Neonatal Opiate Withdrawal SyndromeStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 3
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Crossover
Model description: 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.
Masking: None (open label)
Enrolment: 626 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT05980260
Sponsor's protocol ID: HELP for NOWS 02
Other IDs: 1U24HD107621, 1UG1HD107628, 1UG1HD107580, 1UG1HD107649, 1UG1HD107650, 1UG1HD107653, 1UG1HD107627, 1UG1HD107631
Acronym: OPTimize NOW
Status last verified: Oct 2026
First submitted: 27 Jul 2023
Last updated: 29 Oct 2026
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes
FDA-regulated drug: No
FDA-regulated device: No
Individual data sharing: Yes: 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.

Publications

Devlin LA, Babineau DC, Merhar SL, DeMauro SB, Kraft WK, Lorch SA, Das A, McDonald SA, Rhodes E, Schmidt AF, Trochinski L, Crawford M, Sithisarn T, Leeman L, Kovatis KZ, Ambalavanan N, Smith RW, Telang S, Tioseco JA, McAllister JM, Wexelblatt SL, Muniyappa B, Williams PK, Adeniyi-Jones SC, Hill CD, Wright T, Sokol GM, Johnson L, Hall RW, Duncan SD, Puopolo K, Dummula K, Anderson-Berry A, Davis JM, Poindexter B, Young LW; HEAL Evaluation of Limited Pharmacotherapies for Neonatal Opioid Withdrawal Syndrome (HELP for NOWS) Consortium. Symptom-Based Dosing for Neonatal Opioid Withdrawal: The OPTimize NOW Randomized Clinical Trial. JAMA. 2026 Jun 23;335(24):2114-2125. doi: 10.1001/jama.2026.5782.
PubMed 42033722
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.
PubMed 40866977

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

Not yet recruiting
Recorded Parent/Caregiver Voice for Infants With Neonatal Opioid Withdrawal Syndrome
Neonatal Opioid Withdrawal Syndrome, Prenatal Opioid Exposure
Recruiting
Cerebral Physiology of NOWS
Neonatal Opioid Withdrawal, Neonatal Opioid Withdrawal Syndrome
Active, not recruitingPhase 3
Trial to Shorten Pharmacologic Treatment of Newborns With Neonatal Opioid Withdrawal Syndrome (NOWS)
Neonatal Opioid Withdrawal Syndrome
Active, not recruiting
Neurostimulation to Improve NOWS Outcomes
Neonatal Opioid Withdrawal Syndrome, Neonatal Abstinence Syndrome
RecruitingObservational study
Target Trial Emulation for Pharmacologic Treatment of Neonatal Opioid Withdrawal Syndrome
Neonatal Opioid Withdrawal Syndrome

All Neonatal Opiate Withdrawal Syndrome trials

Study at a glance

From the registry record, last updated by the sponsor on 29 Oct 2026. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Optimizing Pharmacologic Treatment for Neonatal Opioid Withdrawal Syndrome (OPTimize NOW): A Symptom-Based Dosing Approach
ClinicalTrials.gov ID: NCT05980260
Acronym / sponsor ID: OPTimize NOW / HELP for NOWS 02
Conditions: Neonatal Opiate Withdrawal Syndrome
Keywords: NOWS
Phase: Phase 3
Study type: Interventional
Recruitment status: Completed
Enrolment: 626 participants (actual)
Lead sponsor: HELP for NOWS ConsortiumResearch network
Collaborators: National Institutes of Health (NIH), Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Study start: 25 Mar 2024 (actual)
Primary completion: 27 May 2025 (actual)
Study completion: 15 Jul 2025 (actual)
First posted: 7 Aug 2023 (actual)
Results: Posted 29 Oct 2026

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

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.
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

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).

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Crossover
Masking: None (open label)
Number of arms: 2
Model description: 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.

Arm	Type	Receives
Sequence 1	Other	Other: Symptom-based Dosing Approach, Other: Scheduled Opioid Taper ApproachThis 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.
Sequence 2	Other	Other: Symptom-based Dosing Approach, Other: Scheduled Opioid Taper ApproachThis 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.

Who may qualify

Ages: 1 hour to 48 hours
Sex: All
Healthy volunteers: Not accepted
Age groups: Child

Key inclusion criteria (9 listed)

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:
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

Key exclusion criteria (7 listed)

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.

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
Symptom-based Dosing ApproachDuring 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.	Other	Sequence 1, Sequence 2
Scheduled Opioid Taper ApproachDuring 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.	Other	Sequence 1, Sequence 2

Primary outcome

Time From Birth Until Medically Ready for Discharge (ESC Cohort Only)
Time frame: Measured from infant's time of birth to the time of infant's discharge or transfer from the study hospital
Time from birth until infant meets criteria for medically ready for discharge (days). For infants that are not pharmacologically treated, they are considered medically ready for discharge at the actual time of discharge. For infants that are pharmacologically treated, they are considered medically ready for discharge when they are both ≥ 96 hours of age and it has been ≥ 48 hours since their last dose of primary opioid treatment (i.e., morphine, methadone, or buprenorphine). If a pharmacologically treated infant has been discharged by the medical provider before meeting both of those criteria, they are considered medically ready for discharge at the actual time of discharge. This primary outcome is for infants assessed and managed using ESC.

29 secondary outcomes

Time From Birth Until Medically Ready for Discharge (Finnegan Cohort Only)
Time frame: Measured from infant's time of birth to the time of infant's discharge or transfer from the study hospital
Receipt of Pharmacologic Treatment for NOWS (ESC Cohort)
Time frame: Measured from infant's time of birth to the time of infant's discharge or transfer from the study hospital
Length of Hospital Stay (ESC Cohort)
Time frame: Measured from infant's time of birth to the time of infant's discharge or transfer from the study hospital
Total Number Primary Opioid Doses (ESC Cohort)
Time frame: Measured from infant's time of birth to the time of infant's discharge or transfer from the study hospital
Receipt of Secondary Medications for NOWS (ESC Cohort)
Time frame: Measured from infant's time of birth to the time of infant's discharge or transfer from the study hospital
Transition From Treatment With a Symptom-based Dosing Approach to a Scheduled Opioid Taper Approach Due to Persistent Signs of Withdrawal (ESC Cohort)
Time frame: Measured from infant's time of birth to the time of infant's discharge or transfer from the study hospital
Stopped Scheduled Opioid Taper Treatment Due to Excessive Sedation or Respiratory Distress (ESC Cohort)
Time frame: Measured from infant's time of birth to the time of infant's discharge or transfer from the study hospital
Receipt of Pharmacologic Treatment for NOWS (Finnegan Cohort)
Time frame: Measured from infant's time of birth to the time of infant's discharge or transfer from the study hospital
Length of Hospital Stay (Finnegan Cohort)
Time frame: Measured from infant's time of birth to the time of infant's discharge or transfer from the study hospital
Total Number Primary Opioid Doses (Finnegan Cohort)
Time frame: Measured from infant's time of birth to the time of infant's discharge or transfer from the study hospital
Receipt of Secondary Medications for NOWS (Finnegan Cohort)
Time frame: Measured from infant's time of birth to the time of infant's discharge or transfer from the study hospital
Transition From Treatment With a Symptom-based Dosing Approach to a Scheduled Opioid Taper Approach Due to Persistent Signs of Withdrawal (Finnegan Cohort)
Time frame: Measured from infant's time of birth to the time of infant's discharge or transfer from the study hospital
Stopped Scheduled Opioid Taper Treatment Due to Excessive Sedation or Respiratory Distress (Finnegan Cohort)
Time frame: Measured from infant's time of birth to the time of infant's discharge or transfer from the study hospital
Inpatient Composite Safety Outcome for Infants at Risk for Pharmacologic Treatment, Managed With ESC (Present/Absent)
Time frame: Measured from infant's time of birth to the time of infant's discharge or transfer from the study hospital
Inpatient Composite Safety Outcome for Infants at Risk for Pharmacologic Treatment, Managed With Finnegan (Present/Absent)
Time frame: Measured from infant's time of birth to the time of infant's discharge or transfer from the study hospital
Inpatient Composite Critical Safety Outcome for Infants at Risk for Pharmacologic Treatment, Managed With ESC (Present/Absent)
Time frame: Measured from infant's time of birth to the time of infant's discharge or transfer from the study hospital
Inpatient Composite Critical Safety Outcome for Infants at Risk for Pharmacologic Treatment, Managed With Finnegan (Present/Absent)
Time frame: Measured from infant's time of birth to the time of infant's discharge or transfer from the study hospital
Outpatient Composite Safety Outcome at Risk for Pharmacologic Treatment, Managed With ESC (Present/Absent)
Time frame: Measured from infant's time of discharge or transfer from study hospital to time of follow-up chart review at three months of age
Outpatient Composite Safety Outcome at Risk for Pharmacologic Treatment, Managed With Finnegan (Present/Absent)
Time frame: Measured from infant's time of discharge or transfer from study hospital to time of follow-up chart review at three months of age
Outpatient Composite Critical Safety Outcome at Risk for Pharmacologic Treatment, Managed With ESC (Present/Absent)
Time frame: Measured from infant's time of discharge or transfer from study hospital to time of follow-up chart review at three months of age
Outpatient Composite Critical Safety Outcome at Risk for Pharmacologic Treatment, Managed With Finnegan (Present/Absent)
Time frame: Measured from infant's time of discharge or transfer from study hospital to time of follow-up chart review at three months of age
Inpatient Composite Safety Outcome for Infants Treated Pharmacologically, Managed With ESC (Present/Absent)
Time frame: Measured from time that pharmacologic treatment was initiated to the time of infant's discharge or transfer from the study hospital
Inpatient Composite Safety Outcome for Infants Treated Pharmacologically, Managed With Finnegan (Present/Absent)
Time frame: Measured from time that pharmacologic treatment was initiated to the time of infant's discharge or transfer from the study hospital
Inpatient Composite Critical Safety Outcome for Infants Treated Pharmacologically, Managed With ESC (Present/Absent)
Time frame: Measured from time that pharmacologic treatment was initiated to the time of infant's discharge or transfer from the study hospital
Inpatient Composite Critical Safety Outcome for Infants Treated Pharmacologically, Managed With Finnegan (Present/Absent)
Time frame: Measured from time that pharmacologic treatment was initiated to the time of infant's discharge or transfer from the study hospital
Outpatient Composite Safety Outcome for Infants Treated Pharmacologically, Managed With ESC (Present/Absent)
Time frame: Measured from infant's time of discharge or transfer from study hospital to time of follow-up chart review at three months of age
Outpatient Composite Safety Outcome for Infants Treated Pharmacologically, Managed With Finnegan (Present/Absent)
Time frame: Measured from infant's time of discharge or transfer from study hospital to time of follow-up chart review at three months of age
Outpatient Composite Critical Safety Outcome for Infants Treated Pharmacologically, Managed With ESC (Present/Absent)
Time frame: Measured from infant's time of discharge or transfer from study hospital to time of follow-up chart review at three months of age
Outpatient Composite Critical Safety Outcome for Infants Treated Pharmacologically, Managed With Finnegan (Present/Absent)
Time frame: Measured from infant's time of discharge or transfer from study hospital to time of follow-up chart review at three months of age

Results and safety

Results posted to the registry on 29 Oct 2026, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Symptom Based Followed by Scheduled Taper	147	147
Scheduled Taper Followed by Symptom Based	187	187

Primary outcome: Time From Birth Until Medically Ready for Discharge (ESC Cohort Only)

Time frame: Measured from infant's time of birth to the time of infant's discharge or transfer from the study hospital. Mean (95% Confidence Interval). Unit: Days

Measure	Symptom Based n = 189	Scheduled Taper n = 194
Value	9.18 (7.51 to 11.23)	11.61 (10.03 to 13.43)

Symptom Based vs Scheduled Taper: Mean Ratio: 0.79 (95% CI 0.65 to 0.96), p = 0.024, Mixed Models Analysis

Population analysed: Intention-to-Treat (ITT) population for ESC sites, includes all enrolled infants assessed and managed with the ESC care tool. Infants are analyzed according to the dosing approach assigned during the active intervention period ("Symptom Based" or "Scheduled Taper") at their study site at the time of eligibility assessment. Infants assessed and managed with the FNAST care tool are analyzed separately.

29 secondary outcomes are reported in the full results.

Adverse events

Time frame: Adverse Events of Special Interest (AESIs) and Other Adverse Events were collected only during the enrolled infant's initial hospital stay of the study, assessed from infant's birth until time of infant's discharge or transfer from hospital (infant was followed until discharged or transferred from site hospital). Serious Adverse Events and All-Cause Mortality were collected over the entire study duration, assessed from the infant's time of birth to final chart review at 3 months of age.. Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Symptom Based	1 of 306 (0.3%)	4 of 306 (1.3%)	0 of 306
Scheduled Taper	4 of 320 (1.3%)	16 of 320 (5%)	1 of 320
Scheduled Taper (Switched After Receiving Symptom Based)	2 of 91 (2.2%)	2 of 91 (2.2%)	0 of 91

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 29 Oct 2026.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Derived from this study: PubMed 42033722Devlin LA, Babineau DC, Merhar SL, DeMauro SB, Kraft WK, Lorch SA, Das A, McDonald SA, Rhodes E, Schmidt AF, Trochinski L, Crawford M, Sithisarn T, Leeman L, Kovatis KZ, Ambalavanan N, Smith RW, Telang S, Tioseco JA, McAllister JM, Wexelblatt SL, Muniyappa B, Williams PK, Adeniyi-Jones SC, Hill CD, Wright T, Sokol GM, Johnson L, Hall RW, Duncan SD, Puopolo K, Dummula K, Anderson-Berry A, Davis JM, Poindexter B, Young LW; HEAL Evaluation of Limited Pharmacotherapies for Neonatal Opioid Withdrawal Syndrome (HELP for NOWS) Consortium. Symptom-Based Dosing for Neonatal Opioid Withdrawal: The OPTimize NOW Randomized Clinical Trial. JAMA. 2026 Jun 23;335(24):2114-2125. doi: 10.1001/jama.2026.5782.
Derived from this study: PubMed 40866977Young 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.
Related InfoLink provided by the sponsor.
Individual participant dataSharing planned: Yes. 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.

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Lori Devlin, MD principal investigator

University of Louisville

23 sites in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 9 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 29 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 23 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 29 Oct 2026). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Time From Birth Until Medically Ready for Discharge (ESC Cohort Only) (time frame: Measured from infant's time of birth to the time of infant's discharge or transfer from the study hospital). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT05980260, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 29 Oct 2026.