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

Study Overview
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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: 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
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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: Scheduled opioid taper approach for 5 months (Period 1) followed by a two-week washout period following by symptom-based dosing approach for 5 months (Period 2) Symptom-based dosing approach for 5 months (Period 1) followed by a two-week washout period followed by scheduled opioid taper approach for 5 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).

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

Conditions
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Neonatal Opiate Withdrawal Syndrome

Intervention / Treatment
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* Other: Symptom-based Dosing Approach
* Other: Scheduled Opioid Taper Approach


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 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 Exclusion Criteria: 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 two-week washout period.

Ages Eligible for Study
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Minimum Age: 1 Hour
Maximum Age: 48 Hours

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Interventional 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: A scheduled opioid taper approach for 5 months followed by a two-week washout period followed by a symptom-based dosing approach for 5 months. A symptom-based dosing approach for 5 months followed by a two-week washout period followed by a scheduled opioid taper approach for 5 months.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Sequence 1<br>This sequence will assign eligible participants to scheduled opioid taper approach for 5 months followed by a 2-week washout period followed by symptom-based dosing approach for 5 months. | Other: Symptom-based Dosing Approach<br>* 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 (midnight to midnight) 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.<br>Other: Scheduled Opioid Taper Approach<br>* • 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.<br>|
| Other: Sequence 2<br>This sequence will assign eligible participants to symptom-based dosing approach for 5 months followed by a 2-week washout period followed by scheduled opioid taper approach for 5 months. | Other: Symptom-based Dosing Approach<br>* 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 (midnight to midnight) 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.<br>Other: Scheduled Opioid Taper Approach<br>* • 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.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Receipt of pharmacologic treatment | If the infant received opioid replacement therapy, prior to hospital discharge | From date of birth until hospital discharge or 1 year, whichever comes first. | 
| Length of hospital stay | Number of days infant remained in the hospital | From date of birth until hospital discharge or 1 year, whichever comes first. | 
| Total number opioid doses | The total number of opioid doses administered among all infants pharmacologically treated during intital hospitilizatoin. | From date of birth until hospital discharge or 1 year, whichever comes first. | 
| Receipt of secondary medications | The total number of opioid doses administered among all infants pharmacologically treated during intital hospitilizatoin. | From date of birth until hospital discharge or 1 year, whichever comes first. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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NOWS