Clinical trial NCT05980260: Optimizing Pharmacologic Treatment for Neonatal Opioid Withdrawal Syndrome (OPTimize NOW): A Symptom-Based Dosing Approach
Official title: Optimizing Pharmacologic Treatment for Neonatal Opioid Withdrawal Syndrome (OPTimize NOW): A Symptom-Based Dosing Approach
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Neonatal Opiate Withdrawal Syndrome
Keywords: NOWS
Lead sponsor: HELP for NOWS Consortium
Sponsor class: NETWORK
Collaborators: name: National Institutes of Health (NIH)
name: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
First posted: 2023-08-07
Enrollment: 480
Sex: ALL
Minimum age (years): 1
Maximum age (years): 48
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Intervention 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.
Primary purpose: TREATMENT

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).

Eligibility criteria: 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.

Primary outcomes:
measure: Time from birth until medically ready for discharge
timeFrame: From date of birth until hospital discharge or 1 year, whichever comes first.
Secondary outcomes:
measure: Receipt of pharmacologic treatment
timeFrame: From date of birth until hospital discharge or 1 year, whichever comes first.
measure: Length of hospital stay
timeFrame: From date of birth until hospital discharge or 1 year, whichever comes first.
measure: Safety outcomes
timeFrame: From date of birth until 3 months of life
measure: Total number opioid doses
timeFrame: From date of birth until hospital discharge or 1 year, whichever comes first.
measure: Receipt of secondary medications
timeFrame: From date of birth until hospital discharge or 1 year, whichever comes first.
measure: Transition from treatment with a symptom-based dosing approach to a scheduled opioid taper approach
timeFrame: From date of birth until hospital discharge or 1 year, whichever comes first.
measure: Stopped scheduled opioid taper treatment
timeFrame: From date of birth until hospital discharge or 1 year, whichever comes first.
measure: Safety outcomes
timeFrame: From date of birth until hospital discharge or 1 year, whichever comes first.
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama at Birmingham
state: Alabama
city: Little Rock
country: United States
facility: University of Arkansas for Medical Sciences
state: Arkansas
city: Wilmington
country: United States
facility: ChristianaCare
state: Delaware
city: Tampa
country: United States
facility: University of South Florida Health
state: Florida
city: Indianapolis
country: United States
facility: Sidney & Lois Eskenazi Hospital
state: Indiana
city: Jeffersonville
country: United States
facility: University of Louisville Hospital
state: Indiana
city: Kansas City
country: United States
facility: University of Kansas Hospital
state: Kansas
city: Edgewood
country: United States
facility: St. Elizabeth Healthcare
state: Kentucky
city: Lexington
country: United States
facility: Kentucky Children's Hospital
state: Kentucky
city: Louisville
country: United States
facility: Norton Children's Hospital
state: Kentucky
city: Louisville
country: United States
facility: Norton Women's and Children's Hospital
state: Kentucky
city: Omaha
country: United States
facility: University of Nebraska Medical Center
state: Nebraska
city: Atlantic City
country: United States
facility: AtlantiCare Regional Medical Center
state: New Jersey
city: Albuquerque
country: United States
facility: University of New Mexico Health Sciences Center
state: New Mexico
city: Rochester
country: United States
facility: University of Rochester Medical Center
state: New York
city: Cincinnati
country: United States
facility: Good Samaritan Hospital
state: Ohio
city: Cincinnati
country: United States
facility: Cincinnati Children's Hospital Medical Center
state: Ohio
city: Cleveland
country: United States
facility: Rainbow Babies and Children's Hospital
state: Ohio
city: Kettering
country: United States
facility: Kettering Health Main Campus
state: Ohio
city: Oklahoma City
country: United States
facility: Oklahoma Children's Hospital OU Health
state: Oklahoma
city: Philadelphia
country: United States
facility: Children's Hospital of Philadelphia
state: Pennsylvania
city: Philadelphia
country: United States
facility: Pennsylvania Hospital
state: Pennsylvania
city: Philadelphia
country: United States
facility: Thomas Jefferson University Hospital
state: Pennsylvania
city: Salt Lake City
country: United States
facility: University of Utah Health
state: Utah
Study officials:
affiliation: University of Louisville
name: Lori Devlin, MD
role: PRINCIPAL_INVESTIGATOR
References: