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

HELP for NOWS Consortium

Status and phase: Active, not recruiting; Phase 3

Conditions: Neonatal Opiate Withdrawal Syndrome

Treatments: Other: Symptom-based Dosing Approach; Other: Scheduled Opioid Taper Approach

Study type: Interventional

Funder types: NETWORK; NIH

Identifiers

NCT05980260

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)

HELP for NOWS 02

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

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.

Full 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).

Enrollment: 480 estimated patients

Sex: All

Ages: 1 to 48 hours old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: None (Open label)

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480 participants in 2 patient groups

Sequence 1

Other group

Description:

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.

Treatment:

Other: Scheduled Opioid Taper Approach

Other: Symptom-based Dosing Approach

Sequence 2

Other group

Description:

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.

Treatment:

Other: Scheduled Opioid Taper Approach

Other: Symptom-based Dosing Approach