Neonatal Opiate Withdrawal Syndrome
Conditions
Keywords
NOWS
Brief summary
The overall objective is to determine if the ESC care approach will reduce the time until infants being managed for NOWS are medically ready for discharge.
Detailed description
This study will randomize institutions in blocks to transition from usual institutional care for infants with NOWS to the ESC care approach at a randomly allocated transition period (from usual care to the ESC care approach). During the initial birth hospitalization, the clinical site research team will collect data under waiver of consent for infants who meet eligibility criteria. The site research team will obtain informed consent from the legal guardian(s) to obtain long-term outcomes for eligible infants and caregivers. Clinical site research team members may obtain this consent at any point during the hospital stay for infants who meet the trial's inclusion criteria. This data will allow the protocol study team to short- and long-term outcomes for infants managed with the ESC care approach compared to usual institutional care.
Interventions
OTHERFinnegan Neonatal Abstinence Scoring Tool
The FNAST is a scoring system used in neonatal units to initiate and guide therapy in infants of opiate-dependent mothers.
OTHEREat, Sleep, Console (ESC) care tool
The ESC care approach emphasizes parental involvement, simplifies the assessment of infants with NOWS and focuses interventions on non-pharmacologic therapies.
Sponsors
National Institutes of Health (NIH)
Advancing Clinical Trials in Neonatal Opioid Withdrawal (ACT NOW) Program
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
HEALTH_SERVICES_RESEARCH
Masking
SINGLE (Outcomes Assessor)
Masking description
The protocol study team will assure blinding of the electronically performed follow-up questionnaires through the use of a centralized computer scoring system. However, it will not be possible to blind responses to questionnaires that are performed with the assistance of research personnel at the participating sites. The protocol study team will note the method of questionnaire completion and will evaluate for bias in this context.
Intervention model description
Stepped-wedge cluster randomized controlled trial with transition period.All sites start with usual care and are transitioned to using the ESC tool
Eligibility
Sex/Gender
ALL
Age
No minimum to 3 Days
Healthy volunteers
No
Inclusion criteria
* 1\. The infant is being managed for NOWS at an eligible site (i.e., receiving non-pharmacologic care, assessments for withdrawal severity, +/- pharmacologic care) 2. The infant is ≥ 36 weeks gestation 3. The infant satisfies at least 1 of the following criteria: 1. Maternal history of prenatal opioid use 2. Maternal toxicology screen positive for opioids during the second and/or third trimester of pregnancy 3. Infant toxicology screen positive for opioids during the initial hospital stay
Exclusion criteria
* 1\. Infant has major birth defect(s) 2. Infant has neonatal encephalopathy (inclusive of hypoxic ischemic encephalopathy), a metabolic disorder, stroke, intracranial hemorrhage, or meningitis diagnosed by 60 hours of life 3. Infant was receiving respiratory support (any positive pressure or oxygen therapy) unrelated to pharmacologic treatment for NOWS at 60 hours of life 4. Infant was receiving antimicrobial(s) at 60 hours of life 5. Infant has received any major surgical intervention in the first 60 hours of life 6. Postnatal opioid exposure other than for treatment of NOWS in the first 60 hours of life 7. Outborn infants transferred at \>60 hours of life or treated with opioids for NOWS at the transferring hospital
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Time From Birth Until Medically Ready for Discharge | from date of birth until hospital discharge or 1 year whichever comes first | The number of days from birth until the infant is determined to be medically ready for discharge per protocol. The criteria for medical readiness were prospectively defined as an age of at least 96 hours, a period of at least 48 hours without receipt of an opioid, at least 24 hours with no respiratory support and with 100% oral feeding, and at least 24 hours from initiation of maximum caloric density. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Did Infant Receive Opioid Replacement Therapy (Yes/no) | From date of birth until hospital discharge or 1 year whichever comes first | Review of hospital records to determine if infant received opioid replacement therapy prior to hospital discharge |
| Total Dose of Opioid Replacement Therapy Infant Received | From date of birth until hospital discharge or 1 year whichever comes first | If infant received opioid replacement therapy, the units received (mg/kg). |
| Time Until Initiation of Opioid Replacement | From date of birth until hospital discharge or 1 year whichever comes first | If infant received opioid replacement therapy, the timing of the initiation of therapy |
| Receipt of Adjuvant Therapy | from date of birth until hospital discharge or 1 year whichever comes first | To see if the infant had to have any other type of therapy for NOWS (yes/no) |
| Maximum Percent Change in Weight During Initial Birth Hospitalization | from date of birth until hospital discharge or 1 year whichever comes first | Assess percent change in birthweight during hospitalization (i.e., \[minimum weight - birth weight\] / birth weight) |
| Critical Safety Outcome | at 3 months of age. | any non-accidental trauma and death (yes/no) |
| Any Direct Breast Feeding at Discharge | within 24 hours of hospital discharge | Direct breastfeeding within 24 hours of hospital discharge (yes/no) |
| Length of Hospital Stay | from date of birth until hospital discharge or 1 year whichever comes first | Time from birth until infants being managed for NOWS are discharged from the hospital |
| Inpatient Composite Safety Outcome Which Includes Seizures, Accidental Trauma, Respiratory Insufficiency Due to Opioid Therapy (Present/Absent) | from date of birth until hospital discharge or 1 year whichever comes first | composite of the following: seizures, accidental trauma, respiratory insufficiency due to opioid therapy |
| Composite of the Following: Acute/Urgent Care and/or Emergency Room Visits, Hospital Readmissions | at 3 months of age | Outpatient composite safety outcome which includes acute/urgent care and/or emergency room visits, hospital readmissions at 3 months (present/absent) |
| Feeding Type at Discharge (Exclusive Maternal Breast Milk) | from date of birth until hospital discharge or 1 year whichever comes first | Exclusive maternal breast milk feeding at the time of hospital discharge |
Countries
United States
Participant flow
Recruitment details
The in-hospital and initial follow-up portions of the trial were conducted with a waiver of informed consent, as approved by central institutional review board.
Pre-assignment details
The in-hospital portion of the study was performed under waiver of informed consent. Only the newborn babies are considered enrolled participants. The number of participants to start a Period may not equal the number who completed a previous Period because at each subsequent Period a new cohort of newborn babies are enrolled at the respective sites. During the transition period for a given block, sites within the block are not enrolling participants.
Participants by arm
| Arm | Count |
|---|---|
| Usual Care, Finnegan Neonatal Abstinence Scoring Tool Usual institutional care for infants with NOWS with the Finnegan Neonatal Abstinence Scoring Tool (FNAST)
Finnegan Neonatal Abstinence Scoring Tool: The FNAST is a scoring system used in neonatal units to initiate and guide therapy in infants of opiate-dependent mothers. | 702 |
| Eat, Sleep, Console Care Tool New treatment implemented at the site for infants with NOWS using the Eat, Sleep, Console (ESC) care tool
Eat, Sleep, Console (ESC) care tool: The ESC care approach emphasizes parental involvement, simplifies the assessment of infants with NOWS and focuses interventions on non-pharmacologic therapies. | 603 |
| Total | 1,305 |
Baseline characteristics
| Characteristic | Total | Usual Care, Finnegan Neonatal Abstinence Scoring Tool | Eat, Sleep, Console Care Tool |
|---|---|---|---|
| 10-minute Apgar scores | 8 Score on a scale | 8 Score on a scale | 9 Score on a scale |
| 1-minute Apgar scores | 8 Score on a scale | 8 Score on a scale | 8 Score on a scale |
| 5-minute Apgar scores | 9 Score on a scale | 9 Score on a scale | 9 Score on a scale |
| Age, Continuous | 30.7 years STANDARD_DEVIATION 4.7 | 38.6 weeks STANDARD_DEVIATION 1.3 | 31.0 years STANDARD_DEVIATION 4.7 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 140 Participants | 107 Participants | 33 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 1114 Participants | 576 Participants | 538 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 51 Participants | 19 Participants | 32 Participants |
| Gravidity | 4 Pregnancies | 3 Pregnancies | 4 Pregnancies |
| Head circumference at birth | 33.4 cm STANDARD_DEVIATION 1.8 | 33.4 cm STANDARD_DEVIATION 1.9 | 33.5 cm STANDARD_DEVIATION 1.7 |
| Highest Level of Education 8th grade or less | 14 Participants | 8 Participants | 6 Participants |
| Highest Level of Education 9th grade to 12th grade | 119 Participants | 69 Participants | 50 Participants |
| Highest Level of Education College degree | 16 Participants | 7 Participants | 9 Participants |
| Highest Level of Education Graduate degree | 5 Participants | 2 Participants | 3 Participants |
| Highest Level of Education High school diploma | 224 Participants | 125 Participants | 99 Participants |
| Highest Level of Education Partial college or Associate's degree | 119 Participants | 69 Participants | 50 Participants |
| Highest Level of Education Trade or Technical School | 2 Participants | 2 Participants | 0 Participants |
| Highest Level of Education Unknown | 806 Participants | 420 Participants | 386 Participants |
| Infant weight at birth | 3020.1 g STANDARD_DEVIATION 471.8 | 3026.4 g STANDARD_DEVIATION 445.4 | 3012.8 g STANDARD_DEVIATION 490.4 |
| Length at birth | 48.8 cm STANDARD_DEVIATION 2.7 | 48.8 cm STANDARD_DEVIATION 2.6 | 48.8 cm STANDARD_DEVIATION 2.8 |
| Marital Status Married | 200 Participants | 99 Participants | 101 Participants |
| Marital Status Single | 1074 Participants | 582 Participants | 492 Participants |
| Marital Status Unknown | 31 Participants | 21 Participants | 10 Participants |
| Mother's Medical Insurance Other | 3 participants | 0 participants | 3 participants |
| Mother's Medical Insurance Private | 114 participants | 47 participants | 67 participants |
| Mother's Medical Insurance Public Insurance | 1154 participants | 633 participants | 521 participants |
| Mother's Medical Insurance Self-pay/uninsured | 29 participants | 18 participants | 11 participants |
| Mother's Medical Insurance Unknown | 29 participants | 21 participants | 8 participants |
| Parity | 3 Births | 3 Births | 3 Births |
| Race (NIH/OMB) American Indian or Alaska Native | 16 Participants | 12 Participants | 4 Participants |
| Race (NIH/OMB) Asian | 5 Participants | 2 Participants | 3 Participants |
| Race (NIH/OMB) Black or African American | 176 Participants | 104 Participants | 72 Participants |
| Race (NIH/OMB) More than one race | 7 Participants | 1 Participants | 6 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 15 Participants | 4 Participants | 11 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 51 Participants | 24 Participants | 27 Participants |
| Race (NIH/OMB) White | 1035 Participants | 555 Participants | 480 Participants |
| Region of Enrollment United States | 1305 participants | 702 participants | 603 participants |
| Sex: Female, Male Female | 650 Participants | 702 Participants | 603 Participants |
| Sex: Female, Male Male | 0 Participants | 366 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 4 / 702 | 0 / 603 |
| other Total, other adverse events | 8 / 702 | 18 / 603 |
| serious Total, serious adverse events | 4 / 702 | 12 / 603 |
Outcome results
Primary
Time From Birth Until Medically Ready for Discharge
The number of days from birth until the infant is determined to be medically ready for discharge per protocol. The criteria for medical readiness were prospectively defined as an age of at least 96 hours, a period of at least 48 hours without receipt of an opioid, at least 24 hours with no respiratory support and with 100% oral feeding, and at least 24 hours from initiation of maximum caloric density.
Time frame: from date of birth until hospital discharge or 1 year whichever comes first
Population: The primary analysis population only included those infants that met the definition of medically ready for discharge.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Usual Care, Finnegan Neonatal Abstinence Scoring Tool | Time From Birth Until Medically Ready for Discharge | 14.9 days |
| Eat, Sleep, Console Care Tool | Time From Birth Until Medically Ready for Discharge | 8.2 days |
p-value: <0.000195% CI: [0.46, 0.65]Mixed Models Analysis
Secondary
Any Direct Breast Feeding at Discharge
Direct breastfeeding within 24 hours of hospital discharge (yes/no)
Time frame: within 24 hours of hospital discharge
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Usual Care, Finnegan Neonatal Abstinence Scoring Tool | Any Direct Breast Feeding at Discharge | 19.5 percentage of direct breast feeding |
| Eat, Sleep, Console Care Tool | Any Direct Breast Feeding at Discharge | 32.7 percentage of direct breast feeding |
95% CI: [1.13, 2.48]
Secondary
Composite of the Following: Acute/Urgent Care and/or Emergency Room Visits, Hospital Readmissions
Outpatient composite safety outcome which includes acute/urgent care and/or emergency room visits, hospital readmissions at 3 months (present/absent)
Time frame: at 3 months of age
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Usual Care, Finnegan Neonatal Abstinence Scoring Tool | Composite of the Following: Acute/Urgent Care and/or Emergency Room Visits, Hospital Readmissions | 113 Participants |
| Eat, Sleep, Console Care Tool | Composite of the Following: Acute/Urgent Care and/or Emergency Room Visits, Hospital Readmissions | 86 Participants |
95% CI: [0.71, 1.47]
Secondary
Critical Safety Outcome
any non-accidental trauma and death (yes/no)
Time frame: at 3 months of age.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Usual Care, Finnegan Neonatal Abstinence Scoring Tool | Critical Safety Outcome | 5 number of non-accidental trauma/death |
| Eat, Sleep, Console Care Tool | Critical Safety Outcome | 1 number of non-accidental trauma/death |
Secondary
Did Infant Receive Opioid Replacement Therapy (Yes/no)
Review of hospital records to determine if infant received opioid replacement therapy prior to hospital discharge
Time frame: From date of birth until hospital discharge or 1 year whichever comes first
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Usual Care, Finnegan Neonatal Abstinence Scoring Tool | Did Infant Receive Opioid Replacement Therapy (Yes/no) | 328 Participants |
| Eat, Sleep, Console Care Tool | Did Infant Receive Opioid Replacement Therapy (Yes/no) | 145 Participants |
p-value: <0.000195% CI: [0.3, 0.47]Mixed-effect Poisson w/ robust err var
Secondary
Feeding Type at Discharge (Exclusive Maternal Breast Milk)
Exclusive maternal breast milk feeding at the time of hospital discharge
Time frame: from date of birth until hospital discharge or 1 year whichever comes first
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Usual Care, Finnegan Neonatal Abstinence Scoring Tool | Feeding Type at Discharge (Exclusive Maternal Breast Milk) | 6.3 percentage of exclusive breast milk |
| Eat, Sleep, Console Care Tool | Feeding Type at Discharge (Exclusive Maternal Breast Milk) | 12.1 percentage of exclusive breast milk |
95% CI: [0.94, 3.99]
Secondary
Inpatient Composite Safety Outcome Which Includes Seizures, Accidental Trauma, Respiratory Insufficiency Due to Opioid Therapy (Present/Absent)
composite of the following: seizures, accidental trauma, respiratory insufficiency due to opioid therapy
Time frame: from date of birth until hospital discharge or 1 year whichever comes first
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Usual Care, Finnegan Neonatal Abstinence Scoring Tool | Inpatient Composite Safety Outcome Which Includes Seizures, Accidental Trauma, Respiratory Insufficiency Due to Opioid Therapy (Present/Absent) | 1 Participants |
| Eat, Sleep, Console Care Tool | Inpatient Composite Safety Outcome Which Includes Seizures, Accidental Trauma, Respiratory Insufficiency Due to Opioid Therapy (Present/Absent) | 2 Participants |
Secondary
Length of Hospital Stay
Time from birth until infants being managed for NOWS are discharged from the hospital
Time frame: from date of birth until hospital discharge or 1 year whichever comes first
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Usual Care, Finnegan Neonatal Abstinence Scoring Tool | Length of Hospital Stay | 14.0 days |
| Eat, Sleep, Console Care Tool | Length of Hospital Stay | 7.8 days |
95% CI: [0.49, 0.64]Mixed Models Analysis
Secondary
Maximum Percent Change in Weight During Initial Birth Hospitalization
Assess percent change in birthweight during hospitalization (i.e., \[minimum weight - birth weight\] / birth weight)
Time frame: from date of birth until hospital discharge or 1 year whichever comes first
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Usual Care, Finnegan Neonatal Abstinence Scoring Tool | Maximum Percent Change in Weight During Initial Birth Hospitalization | 7.6 percentage of change in birth weight |
| Eat, Sleep, Console Care Tool | Maximum Percent Change in Weight During Initial Birth Hospitalization | 8.0 percentage of change in birth weight |
95% CI: [-0.3, 1]Mixed Models Analysis
Secondary
Receipt of Adjuvant Therapy
To see if the infant had to have any other type of therapy for NOWS (yes/no)
Time frame: from date of birth until hospital discharge or 1 year whichever comes first
Population: The analysis population for this outcome include only infants who received opioid treatment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Usual Care, Finnegan Neonatal Abstinence Scoring Tool | Receipt of Adjuvant Therapy | 19.4 percentage who received adjuvant therapy |
| Eat, Sleep, Console Care Tool | Receipt of Adjuvant Therapy | 15.7 percentage who received adjuvant therapy |
95% CI: [0.37, 1.76]
Secondary
Time Until Initiation of Opioid Replacement
If infant received opioid replacement therapy, the timing of the initiation of therapy
Time frame: From date of birth until hospital discharge or 1 year whichever comes first
Population: The analysis population for this outcome include only infants who received opioid treatment.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Usual Care, Finnegan Neonatal Abstinence Scoring Tool | Time Until Initiation of Opioid Replacement | 53.0 hours |
| Eat, Sleep, Console Care Tool | Time Until Initiation of Opioid Replacement | 76 hours |
95% CI: [8.1, 37.9]
Secondary
Total Dose of Opioid Replacement Therapy Infant Received
If infant received opioid replacement therapy, the units received (mg/kg).
Time frame: From date of birth until hospital discharge or 1 year whichever comes first
Population: The analysis population for this outcome include only infants who received opioid treatment.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Usual Care, Finnegan Neonatal Abstinence Scoring Tool | Total Dose of Opioid Replacement Therapy Infant Received | 7.5 mg/kg |
| Eat, Sleep, Console Care Tool | Total Dose of Opioid Replacement Therapy Infant Received | 5.3 mg/kg |
95% CI: [-0.4, 4.9]