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

Women and Infants Hospital of Rhode Island

Status and phase: Withdrawn; Phase 3

Conditions: Neonatal Opioid Withdrawal Syndrome

Treatments: Drug: Morphine or Placebo; Drug: Buprenorphine or Placebo

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT04455802

WIH 19-0042

1P20GM125507-01 (U.S. NIH Grant/Contract)

Details and patient eligibility

About

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.

Full 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.

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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0 participants in 2 patient groups

Morphine

Active Comparator group

Description:

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.

Treatment:

Drug: Morphine or Placebo

Drug: Buprenorphine or Placebo

Buprenorphine

Experimental group

Description:

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.

Treatment:

Drug: Morphine or Placebo

Drug: Buprenorphine or Placebo