Sublingual Buprenorphine Treatment for Neonatal Abstinence Syndrome - Pilot Study

NCT02249026 | Unknown Phase 1 DMC

• 1 other identifier: 12-0501
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

Brief Summary

Summary: There have been two published RCTs showing efficacy of buprenorphine treatment for NAS. However these trials excluded an estimated 22-47% of infants requiring pharmacologic treatment; those infants born to mothers with co-dependence on an opiate and a benzodiazepine. Although there are concerns, we anticipate that buprenorphine will be safe in this population. If it is safe, we can include these infants in the large double blind, double-dummy buprenorphine and clonidine vs. morphine and clonidine trial. If on the other hand, these infants have respiratory depression or other adverse events when buprenorphine is given, it will be important to report this study and caution the use of buprenorphine in these infants

Conditions

Drug; Withdrawal Symptoms, Neonatal; Withdrawal; Fetus and Newborn Affected by Other Maternal Medication

Outcome Measures

Primary Outcomes (1)

• Assessment of vital signs

  To determine the in infants with NAS who have in-utero exposure to opiates and BZDs. This is an un-blinded observational safety study. A total of 24 neonates with moderate to severe NAS will be enrolled at ACH and its obstetric affiliate Bayfront Hospital in Florida. 12 of these infants will have a positive screen (described below) for both maternally transferred opiate and BZD. The comparison group of 12 infants will have been exposed to opiates but not to BZDs during the pregnancy. Comparisons will be made both within and between groups. The principle outcome measures will be 1) respiratory function as measured by respiratory rate 2) a combined event score which includes episodes of apnea (\>20 sec apneic pause), bradycardia (\<80 bpm) and oxygen hemoglobin desaturation measured by pulse oximetry (\<90%). Other safety measures will include: blood pressures.

  2-8 weeks

Secondary Outcomes (1)

• To determine BNP levels in blood, urine, and meconium(stool)

  2 - 8 weeks

Study Arms (2)

BZDs + opiate exposure treated with BPN

EXPERIMENTAL

In-utero opiate and BZD exposed neonates + Buprenorphine sub-lingual administered in dose volumes greater than 0.5 mL will be given in 2 aliquots separated by 2 minutes allowing time for the drug to be absorbed.

Drug: BZDs + opiate exposure treated with BPN

Opiates exposure treated with BPN

ACTIVE COMPARATOR

In-utero opiate exposed neonates + Buprenorphine sub-lingual administered in dose volumes greater than 0.5 mL will be given in 2 aliquots separated by 2 minutes allowing time for the drug to be absorbed.

Drug: Opiates exposure treated with BPN

Interventions

BZDs + opiate exposure treated with BPN DRUG

These infants will have been exposed not only to opiates but also to BZDs during pregnancy. Administration of Buprenorphine: The solution will be administered under the tongue followed by the insertion of a pacifier to reduce swallowing. Dose volumes greater than 0.5 mL will be given in 2 aliquots separated by 2 minutes allowing time for the drug to be absorbed. If the infant's withdrawal is not controlled, clonidine will be used as adjunct therapy. The initial dose of clonidine is 6 mcg/kg/day in 4 divided doses given every 6 hours. If signs of withdrawal are not controlled, the dose may be increased by 3mcg/kg/day to a maximum 12 mcg/kg/day divided q 6 hrs.

Also known as: Suboxone, Subutex, Buprenex

BZDs + opiate exposure treated with BPN

Opiates exposure treated with BPN DRUG

These infants will have been exposed not only to opiates during pregnancy. Administration of Buprenorphine: The solution will be administered under the tongue followed by the insertion of a pacifier to reduce swallowing. Dose volumes greater than 0.5 mL will be given in 2 aliquots separated by 2 minutes allowing time for the drug to be absorbed. If the infant's withdrawal is not controlled, clonidine will be used as adjunct therapy. The initial dose of clonidine is 6 mcg/kg/day in 4 divided doses given every 6 hours. If signs of withdrawal are not controlled, the dose may be increased by 3mcg/kg/day to a maximum 12 mcg/kg/day divided q 6 hrs.

Also known as: Suboxone, Subutex, Buprenex

Opiates exposure treated with BPN

Eligibility Criteria

• Age: Up to 7 Days
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Newborns ≥ 35 0/7 wks. Gestation undelivered or \< 12 hours of age at enrollment and within the 72 hrs. after birth at the time of transfer to ACH for pharmacologic treatment for moderate to severe NAS
• Newborns ≥ 2 kg weight at birth (10th % for a 35 0/7 wk. newborn)
• Informed parental

You may not qualify if:

• Newborns \<35 0/7 wks. gestation OR older than 72 hrs. of life at time of transfer to ACH for pharmacologic treatment for moderate to severe NAS
• Major congenital anomalies
• Major concomitant medical illness including antibiotic treatment for greater than 3 days
• Any illness that precludes oral or sublingual medication use
• Infants who have received any drug other than "study drug" to treat their NAS
• Infants requiring drug therapy with any high or moderate CYP3A4 inhibitor or inducer (Appendix A)
• Breastfeeding infants.
• Infants in significant pain requiring medication for comfort (for example those with a fracture).

Sponsors & Collaborators

• Gauda, Estelle B., M.D.: lead
• Johns Hopkins University: collaborator
• Johns Hopkins All Children's Hospital: collaborator

Study Sites (1)

All Children's Hopsital

St. Petersburg, Florida, 33701, United States

RECRUITING

MeSH Terms

Conditions

Substance Withdrawal Syndrome

Interventions

Buprenorphine, Naloxone Drug Combination; Buprenorphine

Condition Hierarchy (Ancestors)

Substance-Related Disorders; Chemically-Induced Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Morphinans; Opiate Alkaloids; Alkaloids; Heterocyclic Compounds; Naloxone; Heterocyclic Compounds, Bridged-Ring; Heterocyclic Compounds, 4 or More Rings; Heterocyclic Compounds, Fused-Ring; Phenanthrenes; Polycyclic Aromatic Hydrocarbons; Polycyclic Compounds; Drug Combinations; Pharmaceutical Preparations

Study Officials

• Estelle B Gauda, MD

  JHMI

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDIV
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 11, 2014
• First Posted: September 25, 2014
• Study Start: October 1, 2014
• Primary Completion: June 1, 2016
• Last Updated: May 6, 2016

Record last verified: 2016-05

Locations

US (1)