Prospective Randomized Blinded Trial to Shorten Pharmacologic Treatment of Newborns With Neonatal Opioid Withdrawal Syndrome (NOWS)
Overview
- Phase
- Phase 3
- Intervention
- Buprenorphine or Placebo
- Conditions
- Neonatal Opioid Withdrawal Syndrome
- Sponsor
- Women and Infants Hospital of Rhode Island
- Locations
- 1
- Primary Endpoint
- Total amount of opioid medication for treatment of NOWS
- Status
- Withdrawn
- Last Updated
- 2 years ago
Overview
Brief Summary
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.
Detailed Description
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.
Investigators
James Padbury
Principal Investigator
Women and Infants Hospital of Rhode Island
Eligibility Criteria
Inclusion Criteria
- •Infant gestational age greater than or equal 36 weeks
- •Mother receiving either methadone from a drug treatment program, buprenorphine from a licensed physician, or an opioid prescription for a documented medical need
- •Mother had at least 2 prenatal appointments.
- •Infant toleration of oral medication administration
- •Infant is considered medically stable by the attending physician
- •Singleton Pregnancy
- •English Speaking
Exclusion Criteria
- •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
- •The mother has had less than 2 prenatal care visits
- •The mother reports excessive alcohol use during pregnancy
- •Mother is less than 18 years of age or is not capable of signing consent
- •The infant has a gestational age less than or equal to 35 weeks and 6 days
- •The infant has dysmorphic features including evidence of aneuploidy
- •The infant is not able to tolerate oral medication administration
- •Multiple gestation pregnancy
- •Hypoxic-ischemic encephalopathy
- •Seizures from etiologies other than NOWS
Arms & Interventions
Morphine
Infants randomized to the morphine arm will start at a dose of 0.06 mg/kg/dose every 4 hours. A buprenorphine placebo will also be given at the same frequency as a faux drug.
Intervention: Buprenorphine or Placebo
Morphine
Infants randomized to the morphine arm will start at a dose of 0.06 mg/kg/dose every 4 hours. A buprenorphine placebo will also be given at the same frequency as a faux drug.
Intervention: Morphine or Placebo
Buprenorphine
Infants randomized to the buprenorphine arm will be started on a dose of 10 mg/kg/dose every 8 hours. A morphine placebo will also be given at the same frequency as a faux drug. Patients can only be randomized to only one arm.
Intervention: Buprenorphine or Placebo
Buprenorphine
Infants randomized to the buprenorphine arm will be started on a dose of 10 mg/kg/dose every 8 hours. A morphine placebo will also be given at the same frequency as a faux drug. Patients can only be randomized to only one arm.
Intervention: Morphine or Placebo
Outcomes
Primary Outcomes
Total amount of opioid medication for treatment of NOWS
Time Frame: Duration of pharmacological treatment with opioid medication while admitted to the hospital up to 30 days
Total amount of opioid medication given to infant for the duration of their hospitalization
Secondary Outcomes
- Length of total stay(During hospitalization for NOWS up to 30 days)
- Cognitive, Language, and Motor Development From 18 Month Old Bayley Neurodevelopmental Assessment(18 months old)
- Length of stay secondary to NOWS(During hospitalization for NOWS up to 30 days)
- Neurobehavioral Profile(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)