Clinical trial NCT01452789
Conditions: Neonatal Abstinence Syndrome
Keywords: neonatal abstinence syndrome buprenorphine morphine pharmacokinetics
Sponsor: Thomas Jefferson University
Start date: 2011-11-01; Completion date: 2016-06-01
Enrollment: 63 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief 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.

Detailed description:
This was a single-site, randomized, double-blind, double-dummy, parallel-group clinical trial. Potential patients were identified in the pre-natal period by staff of the Thomas Jefferson University Family center. Mothers who provided consent were contacted upon admission to TJUH. Inclusion and exclusion criteria were reassessed during the peri-partum period and study details reviewed again with the mother, and where possible, the father of the child. Women admitted to TJUH with in utero exposure to opioids who are not in the Family Center present were screened and approached for consent during their inpatient stay.

Infants at risk for NAS had abstinence assessed using the MOTHER scoring instrument, which is based upon Finnegan Score and will hereafter be called the "NAS score". This is the standard instrument used at TJUH. A need for initiation of treatment was defined as any consecutive 3 scores adding up to ≥ 24 or any single score ≥12, and the clinical decision of the attending physician that the infant requires pharmacologic therapy. Randomization took place following reaching of the threshold for initiation of treatment and a re-review of inclusion and exclusion criteria. Patients were randomized to treatment groups of 1) oral morphine/sublingual placebo for buprenorphine or 2) oral placebo for morphine/sublingual buprenorphine. Randomization was stratified according to in utero exposure to methadone or buprenorphine. Oral morphine or placebo for morphine was administered by mouth every 4 hours, while buprenorphine or placebo for buprenorphine was administered every 8 hours. NAS scores were obtained every 4 hours. Dose assessment took place on a daily basis. If the three previous NAS scores are greater than 24, a dose advancement took place (at the discretion of the neonatologist). Morphine/placebo will be increased by 20% and buprenorphine/placebo will be increased by 25%. NNNS scoring took place for all infants who provide consent at day 2-3 of life, or earlier if pharmacologic treatment is required before this time, on day 10 of life, and in the post therapy period (but no later than corrected post gestational age of 46 weeks).

Arms: arm 1: This is the group that received active sublingual buprenorphine and placebo for oral morphine arm 2: This is the group that received active oral morphine and placebo for sublingual buprenorphine
Interventions: intervention 1: sublingual buprenorphine intervention 2: oral morphine
Intervention descriptions: intervention 1: 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 intervention 2: 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

Protocol documents: