Neonatal Opiate Withdrawal Syndrome
Conditions
Keywords
NOWS
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).
Interventions
OTHERSymptom-based Dosing Approach
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.
OTHERScheduled Opioid Taper Approach
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.
Sponsors
HELP for NOWS Consortium
National Institutes of Health (NIH)
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
NONE
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.
Eligibility
Sex/Gender
ALL
Age
1 Years to 48 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Time from birth until medically ready for discharge (ESC cohort only) | From 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) This primary outcome is for infants assessed and managed using ESC. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time from birth until medically ready for discharge (Finnegan Cohort only) | From 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) This secondary outcome is for infants assessed and managed using Finnegan. |
| Receipt of pharmacologic treatment (ESC Cohort) | From date of birth until hospital discharge or 1 year, whichever comes first. | If the infant received opioid replacement therapy prior to hospital discharge and was managed using ESC. |
| Length of hospital stay (ESC Cohort) | From date of birth until hospital discharge or 1 year, whichever comes first. | Number of days infant remained in the hospital and managed with ESC. |
| Total number opioid doses (ESC Cohort) | From date of birth until hospital discharge or 1 year, whichever comes first. | The total number of opioid doses administered among infants managed with ESC and pharmacologically treated during initial hospitalization. |
| Receipt of secondary medications (ESC Cohort) | From date of birth until hospital discharge or 1 year, whichever comes first. | The total number of secondary opioid doses administered among infants managed with ESC and pharmacologically treated during initial hospitalization. |
| Transition from treatment with a symptom-based dosing approach to a scheduled opioid taper approach (ESC Cohort) | From date of birth until hospital discharge or 1 year, whichever comes first. | The total number of infants managed with ESC and pharmacologically treated during initial hospitalization who transitioned from a symptom-based dosing approach to a scheduled opioid taper approach |
| Stopped scheduled opioid taper treatment (ESC Cohort) | From date of birth until hospital discharge or 1 year, whichever comes first. | The total number of infants managed with ESC and pharmacologically treated during initial hospitalization who were initially treated with a scheduled opioid taper but stopped treatment due to excessive sedation or respiratory depression |
| Receipt of pharmacologic treatment (Finnegan Cohort) | From date of birth until hospital discharge or 1 year, whichever comes first. | If the infant received opioid replacement therapy prior to hospital discharge and was managed using Finnegan. |
| Length of hospital stay (Finnegan Cohort) | From date of birth until hospital discharge or 1 year, whichever comes first. | Number of days infant remained in the hospital and managed with Finnegan. |
| Total number opioid doses (Finnegan Cohort) | From date of birth until hospital discharge or 1 year, whichever comes first. | The total number of opioid doses administered among infants managed with Finnegan and pharmacologically treated during initial hospitalization. |
| Receipt of secondary medications (Finnegan Cohort) | From date of birth until hospital discharge or 1 year, whichever comes first. | The total number of secondary opioid doses administered among infants managed with Finnegan and pharmacologically treated during initial hospitalization. |
| Transition from treatment with a symptom-based dosing approach to a scheduled opioid taper approach (Finnegan Cohort) | From date of birth until hospital discharge or 1 year, whichever comes first. | The total number of infants managed with Finnegan and pharmacologically treated during initial hospitalization who transitioned from a symptom-based dosing approach to a scheduled opioid taper approach |
| Stopped scheduled opioid taper treatment (Finnegan Cohort) | From date of birth until hospital discharge or 1 year, whichever comes first. | The total number of infants managed with Finnegan and pharmacologically treated during initial hospitalization who were initially treated with a scheduled opioid taper but stopped treatment due to excessive sedation or respiratory depression |
| Inpatient Composite Safety Outcome for infants at risk for pharmacologic treatment, managed with ESC (present/absent) | From date of birth until hospital discharge | A composite safety outcome for infants at risk for pharmacologic treatment, managed with ESC, defined as the occurrence of any of the following events between birth and hospital discharge: Seizures, Excessive weight loss \>15% from birthweight |
| Inpatient Composite Safety Outcome for infants at risk for pharmacologic treatment, managed with Finnegan (present/absent) | From birth until hospital discharge | A composite safety outcome for infants at risk for pharmacologic treatment, managed with Finnegan defined as the occurrence of any of the following events between birth and hospital discharge: Seizures, Excessive weight loss \>15% from birthweight |
| Inpatient Composite Critical Safety Outcome for infants at risk for pharmacologic treatment, managed with ESC (present/absent) | From birth until hospital discharge | A composite critical safety outcome for infants at risk for pharmacologic treatment, managed with ESC defined as the occurrence of any of the following events between birth and hospital discharge: Non accidental trauma, Death |
| Inpatient Composite Critical Safety Outcome for infants at risk for pharmacologic treatment, managed with Finnegan (present/absent) | A composite critical safety outcome for infants at risk for pharmacologic treatment, managed with Finnegan defined as the occurrence of any of the following events between birth and hospital discharge: Non accidental trauma, Death | From birth until hospital discharge |
| Outpatient Composite Safety Outcome at risk for pharmacologic treatment, managed with ESC (present/absent) | From hospital discharge to 3 months of age | A composite outpatient safety outcome for infants at risk for pharmacologic treatment, managed with ESC defined as the occurrence of any of the following events between hospital discharge and 3 months of age: Acute/urgent care or emergency room visits, Hospital readmissions |
| Outpatient Composite Safety Outcome at risk for pharmacologic treatment, managed with Finnegan (present/absent) | From hospital discharge to 3 months of age | A composite outpatient safety outcome for infants at risk for pharmacologic treatment, managed with Finnegan defined as the occurrence of any of the following events between hospital discharge and 3 months of age: Acute/urgent care or emergency room visits, Hospital readmissions |
| Outpatient Composite Critical Safety Outcome at risk for pharmacologic treatment, managed with ESC (present/absent) | From hospital discharge to 3 months of age | A composite critical outpatient safety outcome for infants at risk for pharmacologic treatment, managed with ESC defined as the occurrence of any of the following events between hospital discharge and 3 months of age: Non accidental trauma, Death |
| Outpatient Composite Critical Safety Outcome at risk for pharmacologic treatment, managed with Finnegan (present/absent) | From hospital discharge to 3 months of age | A composite critical outpatient safety outcome for infants at risk for pharmacologic treatment, managed with Finnegan defined as the occurrence of any of the following events between hospital discharge and 3 months of age: Non accidental trauma, Death |
| Inpatient Composite Safety Outcome for infants treated pharmacologically, managed with ESC (present/absent) | From birth to hospital discharge | A composite safety outcome for infants treated pharmacologically, managed with ESC, defined as the occurrence of any of the following events between birth and hospital discharge: Seizures; Excessive weight loss \>15% from birthweight |
| Inpatient Composite Safety Outcome for infants treated pharmacologically, managed with Finnegan (present/absent) | From birth to hospital discharge | A composite safety outcome for infants treated pharmacologically, managed with Finnegan, defined as the occurrence of any of the following events between birth and hospital discharge: Seizures; Excessive weight loss \>15% from birthweight. |
| Inpatient Composite Critical Safety Outcome for infants treated pharmacologically, managed with ESC (present/absent) | From birth to hospital discharge | A composite critical safety outcome for infants treated pharmacologically, managed with ESC, defined as the occurrence of any of the following events between birth and hospital discharge: Non accidental trauma; Death. |
| Inpatient Composite Critical Safety Outcome for infants treated pharmacologically, managed with Finnegan (present/absent) | From birth to hospital discharge | A composite critical safety outcome for infants treated pharmacologically, managed with Finnegan, defined as the occurrence of any of the following events between birth and hospital discharge: Non accidental trauma; Death. |
| Outpatient Composite Safety Outcome for infants treated pharmacologically, managed with ESC (present/absent) | From hospital discharge to 3 months of age | A composite outpatient safety outcome for infants treated pharmacologically, managed with ESC, defined as the occurrence of any of the following events between hospital discharge and 3 months of age: Acute/urgent care or emergency room visits; Hospital readmissions. |
| Outpatient Composite Safety Outcome for infants treated pharmacologically, managed with Finnegan (present/absent | From hospital discharge to 3 months of age | A composite outpatient safety outcome for infants treated pharmacologically, managed with Finnegan, defined as the occurrence of any of the following events between hospital discharge and 3 months of age: Acute/urgent care or emergency room visits; Hospital readmissions. |
| Outpatient Composite Critical Safety Outcome for infants treated pharmacologically, managed with ESC (present/absent) | From hospital discharge to 3 months of age | A composite critical outpatient safety outcome for infants treated pharmacologically, managed with ESC, defined as the occurrence of any of the following events between hospital discharge and 3 months of age: Non accidental trauma; Death. |
| Outpatient Composite Critical Safety Outcome for infants treated pharmacologically, managed with Finnegan (present/absent) | From hospital discharge to 3 months of age | A composite critical outpatient safety outcome for infants treated pharmacologically, managed with Finnegan, defined as the occurrence of any of the following events between hospital discharge and 3 months of age: Non accidental trauma; Death. |
Countries
United States
Contacts
PRINCIPAL_INVESTIGATORLori Devlin, MD
University of Louisville
Outcome results
None listed