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

Phase 3
Recruiting
Conditions
Neonatal Opiate Withdrawal Syndrome
Interventions
Other: Symptom-based Dosing Approach
Other: Scheduled Opioid Taper Approach
Registration Number
NCT05980260
Lead Sponsor
HELP for NOWS Consortium
Brief 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. 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

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).

Recruitment & Eligibility

Status
RECRUITING
Sex
All
Target Recruitment
480
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.

Study & Design

Study Type
INTERVENTIONAL
Study Design
CROSSOVER
Arm && Interventions
GroupInterventionDescription
Sequence 2Symptom-based Dosing 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.
Sequence 1Symptom-based Dosing 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 2Scheduled 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.
Sequence 1Scheduled 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.
Primary Outcome Measures
NameTimeMethod
Time from birth until medically ready for dischargeFrom date of birth until hospital discharge or 1 year, whichever comes first.

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)

Secondary Outcome Measures
NameTimeMethod
Length of hospital stayFrom date of birth until hospital discharge or 1 year, whichever comes first.

Number of days infant remained in the hospital

Receipt of pharmacologic treatmentFrom date of birth until hospital discharge or 1 year, whichever comes first.

If the infant received opioid replacement therapy prior to hospital discharge.

Transition from treatment with a symptom-based dosing approach to a scheduled opioid taper approachFrom date of birth until hospital discharge or 1 year, whichever comes first.

The total number of infants pharmacologically treated during intital hospitalization who transitioned from a symptom-based dosing approach to a scheduled opioid taper approach

Safety outcomesFrom date of birth until hospital discharge or 1 year, whichever comes first.

Safety outcomes among infants pharmacologically treated during initial hospitalization including presence or absence of inpatient seizures, excessive weight loss of more than 15% from birthweight, and non-accidental trauma and death, and outpatient acute/urgent care or emergency room visits, hospital readmissions, and non-accidental trauma and death

Total number opioid dosesFrom date of birth until hospital discharge or 1 year, whichever comes first.

The total number of opioid doses administered among all infants pharmacologically treated during initial hospitalization.

Receipt of secondary medicationsFrom date of birth until hospital discharge or 1 year, whichever comes first.

The total number of secondary opioid doses administered among all infants pharmacologically treated during intital hospitalization.

Stopped scheduled opioid taper treatmentFrom date of birth until hospital discharge or 1 year, whichever comes first.

The total number of infants pharmacologically treated during intital hospitalization who were initially treated with a scheduled opioid taper but stopped treatment due to excessive sedation or respiratory depression

Trial Locations

Locations (24)

Kentucky Children's Hospital

🇺🇸

Lexington, Kentucky, United States

Children's Hospital of Philadelphia

🇺🇸

Philadelphia, Pennsylvania, United States

Thomas Jefferson University Hospital

🇺🇸

Philadelphia, Pennsylvania, United States

St. Elizabeth Healthcare

🇺🇸

Edgewood, Kentucky, United States

Pennsylvania Hospital

🇺🇸

Philadelphia, Pennsylvania, United States

Cincinnati Children's Hospital Medical Center

🇺🇸

Cincinnati, Ohio, United States

University of Kansas Hospital

🇺🇸

Kansas City, Kansas, United States

Sidney & Lois Eskenazi Hospital

🇺🇸

Indianapolis, Indiana, United States

University of Louisville Hospital

🇺🇸

Jeffersonville, Indiana, United States

Rainbow Babies and Children's Hospital

🇺🇸

Cleveland, Ohio, United States

Good Samaritan Hospital

🇺🇸

Cincinnati, Ohio, United States

University of New Mexico Health Sciences Center

🇺🇸

Albuquerque, New Mexico, United States

University of Rochester Medical Center

🇺🇸

Rochester, New York, United States

Kettering Health Main Campus

🇺🇸

Kettering, Ohio, United States

University of Arkansas for Medical Sciences

🇺🇸

Little Rock, Arkansas, United States

AtlantiCare Regional Medical Center

🇺🇸

Atlantic City, New Jersey, United States

University of Alabama at Birmingham

🇺🇸

Birmingham, Alabama, United States

University of South Florida Health

🇺🇸

Tampa, Florida, United States

Norton Children's Hospital

🇺🇸

Louisville, Kentucky, United States

Norton Women's and Children's Hospital

🇺🇸

Louisville, Kentucky, United States

University of Nebraska Medical Center

🇺🇸

Omaha, Nebraska, United States

University of Utah Health

🇺🇸

Salt Lake City, Utah, United States

Oklahoma Children's Hospital OU Health

🇺🇸

Oklahoma City, Oklahoma, United States

ChristianaCare

🇺🇸

Wilmington, Delaware, United States

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