Blinded Trial of Buprenorphine or Morphine in the Treatment of the Neonatal Abstinence Syndrome
Condition: Neonatal Abstinence Syndrome
MeSH terms: Neonatal Abstinence Syndrome; Syndrome
Intervention: sublingual buprenorphine; oral morphine
Intervention description: Initial daily dose: 15.9 mcg/kg/day; Initial unit dose: 5.3 mcg/kg q8 hours; Maximum daily dose: 60 mcg/kg/day; Up-titration rate: 25%; Weaning rate: 10%; Cessation Dose: Within 10 or 20% of starting dose; Initial daily dose: 0.4 mg/kg/day; Initial unit dose: 0.07 mg/kg q 4 hours; Maximum daily dose: 1.25 mg/kg/day; Up-titration rate: 20%; Weaning rate: 10%; Cessation Dose: 0.025 mg/kg q 4 hours
Intervention MeSH terms: Morphine; Buprenorphine
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 63.0
Sex: All
Healthy volunteers: No
Keywords: neonatal abstinence syndrome; buprenorphine; morphine; pharmacokinetics

Summary:

      The opioid neonatal abstinence syndrome (NAS) is a condition of withdrawal symptoms after
      utero exposure to opioids. In an open label Phase 1 trial sublingual buprenorphine was
      associated with a ~30% reduction length of treatment compared to standard of care morphine.
      Due to the subjective nature of the scoring instrument, efficacy in a blinded trial is needed
      to unequivocally establish the superiority of buprenorphine over morphine. The primary
      objective of the trial is to compare length of treatment using sublingual buprenorphine or
      oral morphine solution in the pharmacologic treatment of the NAS.
    

Eligibility criteria:

        Inclusion Criteria:

          -  ≥ 37 weeks gestation

          -  Exposure to opiates in utero

          -  Demonstration of signs and symptoms of neonatal abstinence syndrome requiring
             treatment

        Exclusion Criteria:

          -  Major congenital malformations and/or intrauterine growth retardation

          -  Medical illness requiring intensification of medical therapy. This includes, but is
             not limited to suspected sepsis requiring antibiotic therapy.

          -  Hypoglycemia requiring treatment with intravenous dextrose.

          -  Bilirubin >20 mg/dL (The need for phototherapy is not exclusionary)

          -  Concomitant benzodiazepine or severe alcohol abuse , self-report of regular use of
             alcohol or of benzodiazepines use in the past 30 days, and/or receipt of
             benzodiazepines by prescription (as determined by self-report or intake urine) by the
             mother 30 days prior to birth,

          -  Concomitant use of Cytrochrom (CYP) 3A inhibitors (erythromycin, clarithromycin,
             ketoconazole, itraconazole, HIV protease inhibitors) or inducers (rifampin,
             carbamazepine, phenobarbital) prior to initiation of NAS treatment

          -  Seizure activity or other neurologic abnormality

          -  Breast feeding

          -  Inability of mother to give informed consent due to co-morbid psychiatric diagnosis