Buprenorphine for Treatment of Neonatal Abstinence Syndrome in Infants With In Utero Exposure to Benzodiazepines (MOPPlus)

A Randomized, Open Label Clinical Trial of Buprenorphine in the Treatment of Neonatal Abstinence Syndrome in Infants With In Utero Exposure to Benzodiazepines or Are Breastfeeding

The opioid neonatal abstinence syndrome (NAS) is a condition of withdrawal symptoms after utero exposure to opioids. Sublingual buprenorphine shows promise as a new treatment in NAS. This trial will investigate the safety and tolerability of sublingual buprenorphine in infants exposed to both opioids and benzodiazepines in utero or with exposure of opioids in those who are breastfeeding.

Study Overview

• Status: Completed
• Conditions: Neonatal Abstinence Syndrome
• Intervention / Treatment: Drug: sublingual buprenorphine; Drug: oral morphine

Detailed Description

Infants with in utero exposure to opioids often require therapy with morphine for an extended period. In a clinical trial, sublingual buprenorphine reduced this treatment period by ~30%. However, infants with both opioid and benzodiazepine exposure were not included in the trial. This study will test the safety and tolerability of sublingual buprenorphine in infants with in utero exposure to benzodiazepines or who are breastfeeding.

• Study Type: Interventional
• Enrollment (Actual): 11
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19107
      • Thomas Jefferson University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. ≥ 37 weeks gestation
2. Exposure to opioids in utero
3. Demonstration of signs and symptoms of neonatal abstinence syndrome requiring treatment
4. Exposure to benzodiazepines in utero and/or receiving breast milk. Benzodiazepine use is defined as maternal 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.

Exclusion Criteria:

1. Major congenital malformations and/or intrauterine growth retardation defined as birth weight <2200 gm
2. Medical illness requiring intensification of medical therapy. This includes, but is not limited to suspected sepsis requiring antibiotic therapy.
3. Hypoglycemia requiring treatment with intravenous dextrose
4. Bilirubin >20 mg/dL (The need for phototherapy is not exclusionary)
5. Seizure activity or other neurologic abnormality

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: sublingual buprenorphine; 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	Drug: sublingual buprenorphine; Sublingual buprenorphine for the treatment of neonatal abstinence syndrome; Other Names: buprenex
Active Comparator: oral morphine; 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	Drug: oral morphine; Oral morphine for the treatment of neonatal abstinence syndrome; Other Names: morphine

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Length of treatment	This endpoint will compare length of treatment (in days) using sublingual buprenorphine or oral morphine solution.	Patients will be followed for the duration of hospital stay, an expected average of 5 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Length of hospitalization	This endpoint will compare length of stay (in days) using sublingual buprenorphine or oral morphine	Patients will be followed for the duration of hospital stay, an expected average of 5 weeks
Number of patients requiring supplemental phenobarbital treatment	This endpoint will compare requirement number of patients who require use of supplemental phenobarbital for treatment of NAS	Patients will be followed for the duration of hospital stay, an expected average of 5 weeks
Number of participants with adverse events as a measure of safety and tolerability	Adverse events will be collected, graded by severity, and assessed for causality referent to study drug.	Patients will be followed for the duration of hospital stay, an expected average of 5 weeks

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Feeding patterns	To compare the feeding patterns, weight gain, and incidence of feeding dysfunction in infants treated with sublingual buprenorphine and oral morphine for NAS	Patients will be followed for the duration of hospital stay, an expected average of 5 weeks
Respiratory Patterns	To compare the respiratory patterns of infants receiving sublingual buprenorphine or morphine solution for the pharmacologic treatment of NAS after in utero exposure to opioids and benzodiazepines and/or postnatal breast milk.	Patients will be followed for the duration of hospital stay, an expected average of 5 weeks

Collaborators and Investigators

• Sponsor: Thomas Jefferson University
• Investigators: Principal Investigator: Walter K Kraft, MD, Thomas Jefferson University

Study record dates

Study Major Dates

• Study Start: August 1, 2012
• Primary Completion (Actual): September 1, 2016
• Study Completion (Actual): September 1, 2016

Study Registration Dates

• First Submitted: August 20, 2012
• First Submitted That Met QC Criteria: August 20, 2012
• First Posted (Estimate): August 23, 2012

Study Record Updates

• Last Update Posted (Estimate): October 14, 2016
• Last Update Submitted That Met QC Criteria: October 13, 2016
• Last Verified: October 1, 2016

More Information

Terms related to this study

• Keywords: buprenorphine; morphine; benzodiazepine; Neonatal Abstinence Syndrome
• Additional Relevant MeSH Terms: Mental Disorders; Chemically-Induced Disorders; Pathologic Processes; Substance-Related Disorders; Disease; Infant, Newborn, Diseases; Syndrome; Neonatal Abstinence Syndrome; Physiological Effects of Drugs; Central Nervous System Depressants; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Analgesics, Opioid; Narcotics; Narcotic Antagonists; Buprenorphine; Morphine
• Other Study ID Numbers: 12D.398