Randomized Control Trial of Buprenorphine vs. Morphine for the Treatment of Neonatal Opioid Withdrawal Syndrome (NOWS)

Women and Infants Hospital of Rhode Island

Overview

This randomized control trial will compare buprenorphine and morphine, two currently used medications for the treatment of neonatal opioid withdrawal syndrome (NOWS), in newborns to determine which medication will reduce the number of days of pharmacological treatment.

This randomized control trial will compare buprenorphine to morphine, two currently used medications for the treatment of NOWS, to determine whether the use of buprenorphine for NOWS treatment will reduce the number of days of pharmacological treatment. After an infant is born they will be monitored for signs of NOWS. Once an infant reaches treatment thresholds, they will be randomized using a double dummy design to either the buprenorphine or morphine treatment arm. After randomization infants will receive a syringe with either morphine or placebo every 4 hours and every 8 hours infant will receive 1 sublingual application of buprenorphine or placebo. To maintain the blind infants enrolled in the study will receive both interventions. During the study medication doses will be weaned by 10% of the stabilization dose. Study intervention will continue until 20 percent of the maximal dose has been reached. Use of a second line drug will be permissible after randomization and after an infant has had 2 consecutive escalations. Second line drug will be phenobarbital, in addition to the study drug. Infants in both groups will be evaluated and scored for NOWS symptoms to determine if weaning study medication is permissible each day. NOWS scores that do not reach the threshold for escalation will wean in accordance with standard clinical practice. If NOWS symptoms increase during treatment, infants will have the dose of the study drug increased by 10% to the previous day's dose. When stable for 24 hours, the weaning process will continue. The NICU Network Neurobehavioral Scale (NNNS) will be administered prior to starting study medication and once off study medication but prior to discharge to examine proportion of infants in each medication arm for the abnormal NNNS profiles which has been associated with atypical early childhood outcomes including behavior problems and low IQ scores. Development at 18 months of age will also be assessed to examine any differences in both arms of the study.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Conditions

Neonatal Opioid Withdrawal Syndrome

Interventions

Buprenorphine or PlaceboDRUG

The double blind, double dummy design necessitates that both drugs be on an identical schedule. The 4-hour dosing allows for this pairing. If a patient is randomized to the buprenorphine arm, medication administration will follow an every 8-hour dosing but medication will be substituted with placebo during the intermediary time point.

Morphine or PlaceboDRUG

If a patient is randomized to the morphine arm, morphine will be given every 4 hours. Placebo will also be given at the same frequency as a faux drug.

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

Inclusion Criteria: 1. Infant gestational age greater than or equal 36 weeks 2. Mother receiving either methadone from a drug treatment program, buprenorphine from a licensed physician, or an opioid prescription for a documented medical need 3. Mother had at least 2 prenatal appointments. 4. Infant toleration of oral medication administration 5. Infant is considered medically stable by the attending physician 6. Singleton Pregnancy 7. English Speaking Exclusion Criteria: 1. Within 30 days of birth the mother has actively used illicit drugs (excluding THC) or obtaining oral opioids, methadone, or buprenorphine from a non-licensed physician or drug treatment program 2. The mother has had less than 2 prenatal care visits 3. The mother reports excessive alcohol use during pregnancy 4. Mother is less than 18 years of age or is not capable of signing consent 5. The infant has a gestational age less than or equal to 35 weeks and 6 days 6. The infant has dysmorphic features including evidence of aneuploidy 7. The infant is not able to tolerate oral medication administration 8. Multiple gestation pregnancy 9. Hypoxic-ischemic encephalopathy 10. Seizures from etiologies other than NOWS 11. Non-English Speaking 12. Infant started on NOWS standard care medication prior to study consent

Locations (1)

Women and Infants Hospital

Providence, Rhode Island, United States

Outcomes

Primary Outcomes

Total amount of opioid medication for treatment of NOWS

Total amount of opioid medication given to infant for the duration of their hospitalization

Time frame: Duration of pharmacological treatment with opioid medication while admitted to the hospital up to 30 days

Secondary Outcomes

Length of total stay

Length of hospital stay due to NOWS

Time frame: During hospitalization for NOWS up to 30 days

Length of stay secondary to NOWS

Total length of hospital stay secondary to NOWS

Time frame: During hospitalization for NOWS up to 30 days

Neurobehavioral Profile

Neurobehavior will be assessed with Neonatal Intensive Care Unit (NICU) Network Neurobehavioral Scale (NNNS). The NNNS is a comprehensive evaluation of neurologic and behavioral functioning as well as signs of stress. Profile 5 is the most atypical, and is characterized by exaggerated scores for arousal, excitability, hypertonicity, quality of movement, and stress abstinence. The atypical profile as been associated with atypical early childhood outcomes, including more behavior problems and lower IQ scores. Researchers will compare the proportion of atypical neurobehavioral profiles for infants in each intervention arm.

Time frame: At birth before randomization to NOWS treatment arm around 18-24 hours of life and prior to hospital discharge up to 30 days of life

Cognitive, Language, and Motor Development From 18 Month Old Bayley Neurodevelopmental Assessment

The Bayley Scales of Infant and Toddler Development (BSID-III) assesses the development of infants and children (1-42 months) through a series of developmental play tasks, identifying children with developmental delay. Raw scores of completed items are summarized within three distinct scale scores (Cognitive Scale, Language Scale, Motor Scale). Scale scores are each converted to composite scores to determine the child's performance compared with scores of age-matched children of typical development (percentile rank). A higher composite score indicates more ideal developmental outcome (range 40-160). At 18 month follow-up visit, participants were assessed using the BSID-III for composite score outcomes.

Data from ClinicalTrials.gov

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