Blinded Trial of Buprenorphine or Morphine in the Treatment of the Neonatal Abstinence Syndrome

NCT01452789 | Completed Phase 3 Results DMC

• 2 other identifiers: 11F.193R01DA029076-01A1
• Study Type: interventional
• Target: 63
• Locations: 1 country
• Sites: 1

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.

Conditions

Neonatal Abstinence Syndrome

Keywords

neonatal abstinence syndrome; buprenorphine; morphine; pharmacokinetics

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (3)

• Length of Hospitalization

  Duration of hospital stay is an expected average of 5 weeks.

• Number of Patients Requiring Supplemental Phenobarbital Treatment.

  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

  Patients will be followed for the duration of hospital stay, an expected average of 5 weeks.

Study Arms (2)

sublingual buprenorphine

EXPERIMENTAL

This is the group that received active sublingual buprenorphine and placebo for oral morphine

Drug: sublingual buprenorphine

oral morphine

ACTIVE COMPARATOR

This is the group that received active oral morphine and placebo for sublingual buprenorphine

Drug: oral morphine

Interventions

sublingual buprenorphine DRUG

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

Also known as: Buprenex

sublingual buprenorphine

oral morphine DRUG

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

oral morphine

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• ≥ 37 weeks gestation
• Exposure to opiates in utero
• Demonstration of signs and symptoms of neonatal abstinence syndrome requiring treatment

You may not qualify if:

• 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.
• 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

Sponsors & Collaborators

• Thomas Jefferson University: lead
• National Institute on Drug Abuse (NIDA): collaborator

Study Sites (1)

Thomas Jefferson University Hosptial

Philadelphia, Pennsylvania, 19107, United States

Location

Related Publications (4)

• Kraft WK, Dysart K, Greenspan JS, Gibson E, Kaltenbach K, Ehrlich ME. Revised dose schema of sublingual buprenorphine in the treatment of the neonatal opioid abstinence syndrome. Addiction. 2011 Mar;106(3):574-80. doi: 10.1111/j.1360-0443.2010.03170.x. Epub 2010 Oct 6.

  PMID: 20925688 BACKGROUND

• Kraft WK, Gibson E, Dysart K, Damle VS, Larusso JL, Greenspan JS, Moody DE, Kaltenbach K, Ehrlich ME. Sublingual buprenorphine for treatment of neonatal abstinence syndrome: a randomized trial. Pediatrics. 2008 Sep;122(3):e601-7. doi: 10.1542/peds.2008-0571. Epub 2008 Aug 11.

  PMID: 18694901 BACKGROUND

• Zankl A, Martin J, Davey JG, Osborn DA. Opioid treatment for opioid withdrawal in newborn infants. Cochrane Database Syst Rev. 2021 Jul 7;7(7):CD002059. doi: 10.1002/14651858.CD002059.pub4.

  PMID: 34231914 DERIVED

• Kraft WK, Adeniyi-Jones SC, Chervoneva I, Greenspan JS, Abatemarco D, Kaltenbach K, Ehrlich ME. Buprenorphine for the Treatment of the Neonatal Abstinence Syndrome. N Engl J Med. 2017 Jun 15;376(24):2341-2348. doi: 10.1056/NEJMoa1614835. Epub 2017 May 4.

  PMID: 28468518 DERIVED

MeSH Terms

Conditions

Neonatal Abstinence Syndrome

Interventions

Buprenorphine; Morphine

Condition Hierarchy (Ancestors)

Infant, Newborn, Diseases; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Substance-Related Disorders; Chemically-Induced Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Morphinans; Opiate Alkaloids; Alkaloids; Heterocyclic Compounds; Heterocyclic Compounds, Bridged-Ring; Heterocyclic Compounds, 4 or More Rings; Heterocyclic Compounds, Fused-Ring; Phenanthrenes; Polycyclic Aromatic Hydrocarbons; Polycyclic Compounds; Morphine Derivatives

Results Point of Contact

• Title: Walter Kraft
• Organization: Thomas Jefferson University

walter.kraft@jefferson.edu

215 955 9077

Study Officials

• Walter K Kraft, MD

  Thomas Jeffeson University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 4, 2011
• First Posted: October 17, 2011
• Study Start: November 1, 2011
• Primary Completion: June 1, 2016
• Study Completion: June 1, 2016
• Last Updated: March 24, 2020
• Results First Posted: March 24, 2020

Record last verified: 2020-03

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: Available after Jan. 1, 2020
• Access Criteria: PI and co-investigators will have discretion to share data with potential collaborators.

Locations

US (1)