Randomized Control Trial of Buprenorphine vs. Morphine for the Treatment of Neonatal Opioid Withdrawal Syndrome (NOWS)

NCT04455802 | Withdrawn Phase 3 DMC FDA Drug

• 2 other identifiers: WIH 19-00421P20GM125507-01
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

This randomized control trial will compare buprenorphine and morphine, two currently used medications for the treatment of neonatal opioid withdrawal syndrome (NOWS), in newborns to determine which medication will reduce the number of days of pharmacological treatment.

Conditions

Neonatal Opioid Withdrawal Syndrome

Keywords

Neonatal Opioid Withdrawal Syndrome; Neonatal Abstinence Syndrome

Outcome Measures

Primary Outcomes (1)

• Total amount of opioid medication for treatment of NOWS

  Total amount of opioid medication given to infant for the duration of their hospitalization

  Duration of pharmacological treatment with opioid medication while admitted to the hospital up to 30 days

Secondary Outcomes (4)

• Length of total stay

  During hospitalization for NOWS up to 30 days

• Length of stay secondary to NOWS

  During hospitalization for NOWS up to 30 days

• Neurobehavioral Profile

  At birth before randomization to NOWS treatment arm around 18-24 hours of life and prior to hospital discharge up to 30 days of life

• Cognitive, Language, and Motor Development From 18 Month Old Bayley Neurodevelopmental Assessment

  18 months old

Study Arms (2)

Morphine

ACTIVE COMPARATOR

Infants randomized to the morphine arm will start at a dose of 0.06 mg/kg/dose every 4 hours. A buprenorphine placebo will also be given at the same frequency as a faux drug.

Drug: Buprenorphine or Placebo; Drug: Morphine or Placebo

Buprenorphine

EXPERIMENTAL

Infants randomized to the buprenorphine arm will be started on a dose of 10 mg/kg/dose every 8 hours. A morphine placebo will also be given at the same frequency as a faux drug. Patients can only be randomized to only one arm.

Drug: Buprenorphine or Placebo; Drug: Morphine or Placebo

Interventions

Buprenorphine or Placebo DRUG

The double blind, double dummy design necessitates that both drugs be on an identical schedule. The 4-hour dosing allows for this pairing. If a patient is randomized to the buprenorphine arm, medication administration will follow an every 8-hour dosing but medication will be substituted with placebo during the intermediary time point.

Buprenorphine; Morphine

Morphine or Placebo DRUG

If a patient is randomized to the morphine arm, morphine will be given every 4 hours. Placebo will also be given at the same frequency as a faux drug.

Buprenorphine; Morphine

Eligibility Criteria

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

You may qualify if:

• Infant gestational age greater than or equal 36 weeks
• Mother receiving either methadone from a drug treatment program, buprenorphine from a licensed physician, or an opioid prescription for a documented medical need
• Mother had at least 2 prenatal appointments.
• Infant toleration of oral medication administration
• Infant is considered medically stable by the attending physician
• Singleton Pregnancy
• English Speaking

You may not qualify if:

• Within 30 days of birth the mother has actively used illicit drugs (excluding THC) or obtaining oral opioids, methadone, or buprenorphine from a non-licensed physician or drug treatment program
• The mother has had less than 2 prenatal care visits
• The mother reports excessive alcohol use during pregnancy
• Mother is less than 18 years of age or is not capable of signing consent
• The infant has a gestational age less than or equal to 35 weeks and 6 days
• The infant has dysmorphic features including evidence of aneuploidy
• The infant is not able to tolerate oral medication administration
• Multiple gestation pregnancy
• Hypoxic-ischemic encephalopathy
• Seizures from etiologies other than NOWS
• Non-English Speaking
• Infant started on NOWS standard care medication prior to study consent

Sponsors & Collaborators

• Women and Infants Hospital of Rhode Island: lead
• National Institute of General Medical Sciences (NIGMS): collaborator

Study Sites (1)

Women and Infants Hospital

Providence, Rhode Island, 02905, United States

Location

Related Publications (10)

• Lester BM, Tronick EZ, Brazelton TB. The Neonatal Intensive Care Unit Network Neurobehavioral Scale procedures. Pediatrics. 2004 Mar;113(3 Pt 2):641-67.

  PMID: 14993524 BACKGROUND

• Davis JM, Shenberger J, Terrin N, Breeze JL, Hudak M, Wachman EM, Marro P, Oliveira EL, Harvey-Wilkes K, Czynski A, Engelhardt B, D'Apolito K, Bogen D, Lester B. Comparison of Safety and Efficacy of Methadone vs Morphine for Treatment of Neonatal Abstinence Syndrome: A Randomized Clinical Trial. JAMA Pediatr. 2018 Aug 1;172(8):741-748. doi: 10.1001/jamapediatrics.2018.1307.

  PMID: 29913015 BACKGROUND

• Kraft WK, Adeniyi-Jones SC, Ehrlich ME. Buprenorphine for the Neonatal Abstinence Syndrome. N Engl J Med. 2017 Sep 7;377(10):997-998. doi: 10.1056/NEJMc1709121. No abstract available.

  PMID: 28877016 BACKGROUND

• Brown MS, Hayes MJ, Thornton LM. Methadone versus morphine for treatment of neonatal abstinence syndrome: a prospective randomized clinical trial. J Perinatol. 2015 Apr;35(4):278-83. doi: 10.1038/jp.2014.194. Epub 2014 Oct 30.

  PMID: 25357093 BACKGROUND

• Asti L, Magers JS, Keels E, Wispe J, McClead RE Jr. A quality improvement project to reduce length of stay for neonatal abstinence syndrome. Pediatrics. 2015 Jun;135(6):e1494-500. doi: 10.1542/peds.2014-1269. Epub 2015 May 4.

  PMID: 25941308 BACKGROUND

• Devlin LA, Lau T, Radmacher PG. Decreasing Total Medication Exposure and Length of Stay While Completing Withdrawal for Neonatal Abstinence Syndrome during the Neonatal Hospital Stay. Front Pediatr. 2017 Oct 10;5:216. doi: 10.3389/fped.2017.00216. eCollection 2017.

  PMID: 29067285 BACKGROUND

• 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

• Hall ES, Rice WR, Folger AT, Wexelblatt SL. Comparison of Neonatal Abstinence Syndrome Treatment with Sublingual Buprenorphine versus Conventional Opioids. Am J Perinatol. 2018 Mar;35(4):405-412. doi: 10.1055/s-0037-1608634. Epub 2017 Nov 7.

  PMID: 29112997 BACKGROUND

• Moore JN, Gastonguay MR, Ng CM, Adeniyi-Jones SC, Moody DE, Fang WB, Ehrlich ME, Kraft WK. The Pharmacokinetics and Pharmacodynamics of Buprenorphine in Neonatal Abstinence Syndrome. Clin Pharmacol Ther. 2018 Jun;103(6):1029-1037. doi: 10.1002/cpt.1064. Epub 2018 Apr 28.

  PMID: 29516490 BACKGROUND

• Anagnostis EA, Sadaka RE, Sailor LA, Moody DE, Dysart KC, Kraft WK. Formulation of buprenorphine for sublingual use in neonates. J Pediatr Pharmacol Ther. 2011 Oct;16(4):281-4. doi: 10.5863/1551-6776-16.4.281.

  PMID: 22768012 BACKGROUND

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

Study Officials

• Adam J Czynski, DO

  Women and Infants Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: The study will be a randomized, double-blind, double-dummy, intention-to-treat clinical trial. All clinical providers, research personnel and participants will be blinded to group assignment. Pharmacy personnel will be the only un-blinded individuals. The placebo medication will be identical in appearance and volume to a dose of the medication at the respective dose.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Model Details: Infants will be randomly assigned to treatment arms of either morphine or buprenorphine

Study Record Dates

• First Submitted: June 8, 2020
• First Posted: July 2, 2020
• Study Start: October 1, 2020
• Primary Completion: May 17, 2021
• Study Completion: May 17, 2021
• Last Updated: June 22, 2023

Record last verified: 2023-06

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)