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

10 maart 2020 bijgewerkt door: Thomas Jefferson University

A Randomized, Active-Control, Double-Blind, Double-Dummy Clinical Trial Comparing Sublingual Buprenorphine And Morphine Solution For The Treatment Of Neonatal Opioid Abstinence Syndrome

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.

Studie Overzicht

Toestand

Voltooid

Conditie

Interventie / Behandeling

Gedetailleerde beschrijving

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).

Studietype

Ingrijpend

Inschrijving (Werkelijk)

63

Fase

  • Fase 3

Contacten en locaties

In dit gedeelte vindt u de contactgegevens van degenen die het onderzoek uitvoeren en informatie over waar dit onderzoek wordt uitgevoerd.

Studie Locaties

  • Verenigde Staten
    • Pennsylvania
      • Philadelphia, Pennsylvania, Verenigde Staten, 19107
        • Thomas Jefferson University Hosptial

Deelname Criteria

Onderzoekers zoeken naar mensen die aan een bepaalde beschrijving voldoen, de zogenaamde geschiktheidscriteria. Enkele voorbeelden van deze criteria zijn iemands algemene gezondheidstoestand of eerdere behandelingen.

Geschiktheidscriteria

Leeftijden die in aanmerking komen voor studie

  • Kind
  • Volwassen
  • Oudere volwassene

Accepteert gezonde vrijwilligers

Nee

Geslachten die in aanmerking komen voor studie

Allemaal

Beschrijving

Inclusion Criteria:

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

Exclusion Criteria:

  • 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.
  • Bilirubin >20 mg/dL (The need for phototherapy is not exclusionary)
  • 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

Studie plan

Dit gedeelte bevat details van het studieplan, inclusief hoe de studie is opgezet en wat de studie meet.

Hoe is de studie opgezet?

Ontwerpdetails

  • Primair doel: Behandeling
  • Toewijzing: Gerandomiseerd
  • Interventioneel model: Parallelle opdracht
  • Masker: Verviervoudigen

Wapens en interventies

Deelnemersgroep / Arm
Interventie / Behandeling
Experimenteel: sublingual buprenorphine
This is the group that received active sublingual buprenorphine and placebo for oral morphine
Geneesmiddel: 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
Andere namen:
  • Buprenex
Actieve vergelijker: oral morphine
This is the group that received active oral morphine and placebo for sublingual buprenorphine
Geneesmiddel: 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

Wat meet het onderzoek?

Primaire uitkomstmaten

Uitkomstmaat
Maatregel Beschrijving
Tijdsspanne
Length of Treatment
Tijdsspanne: Patients will be followed for the duration of hospital stay, an expected average of 5 weeks.
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.

Secundaire uitkomstmaten

Uitkomstmaat
Maatregel Beschrijving
Tijdsspanne
Length of Hospitalization
Tijdsspanne: Duration of hospital stay is an expected average of 5 weeks.
This endpoint will compare length of stay in the hospital (in days) using sublingual buprenorphine or morphine solution.
Duration of hospital stay is an expected average of 5 weeks.
Number of Patients Requiring Supplemental Phenobarbital Treatment.
Tijdsspanne: Patients will be followed for the duration of hospital stay, an expected average of 5 weeks.
This endpoint will compare requirement number of patients who require use of supplemental phenobarbital.
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
Tijdsspanne: Patients will be followed for the duration of hospital stay, an expected average of 5 weeks.
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.

Medewerkers en onderzoekers

Hier vindt u mensen en organisaties die betrokken zijn bij dit onderzoek.

Sponsor

Thomas Jefferson University

Medewerkers

National Institute on Drug Abuse (NIDA)

Onderzoekers

  • Hoofdonderzoeker: Walter K Kraft, MD, Thomas Jeffeson University

Publicaties en nuttige links

De persoon die verantwoordelijk is voor het invoeren van informatie over het onderzoek stelt deze publicaties vrijwillig ter beschikking. Dit kan gaan over alles wat met het onderzoek te maken heeft.

Algemene publicaties

Studie record data

Deze datums volgen de voortgang van het onderzoeksdossier en de samenvatting van de ingediende resultaten bij ClinicalTrials.gov. Studieverslagen en gerapporteerde resultaten worden beoordeeld door de National Library of Medicine (NLM) om er zeker van te zijn dat ze voldoen aan specifieke kwaliteitscontrolenormen voordat ze op de openbare website worden geplaatst.

Bestudeer belangrijke data

Studie start

1 november 2011

Primaire voltooiing (Werkelijk)

1 juni 2016

Studie voltooiing (Werkelijk)

1 juni 2016

Studieregistratiedata

Eerst ingediend

4 oktober 2011

Eerst ingediend dat voldeed aan de QC-criteria

14 oktober 2011

Eerst geplaatst (Schatting)

17 oktober 2011

Updates van studierecords

Laatste update geplaatst (Werkelijk)

24 maart 2020

Laatste update ingediend die voldeed aan QC-criteria

10 maart 2020

Laatst geverifieerd

1 maart 2020

Meer informatie

Termen gerelateerd aan deze studie

Trefwoorden

Aanvullende relevante MeSH-voorwaarden

Andere studie-ID-nummers

  • 11F.193
  • R01DA029076-01A1 (Subsidie/contract van de Amerikaanse NIH)

Plan Individuele Deelnemersgegevens (IPD)

Bent u van plan om gegevens van individuele deelnemers (IPD) te delen?

JA

Beschrijving IPD-plan

Interested investigators should contact the PI listed on clinicaltrials.gov. Study protocol, statistical action plan and informed consent are available in the public domain as a supplement to the publication https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5662132/

IPD-tijdsbestek voor delen

Available after Jan. 1, 2020

IPD-toegangscriteria voor delen

PI and co-investigators will have discretion to share data with potential collaborators.

IPD delen Ondersteunend informatietype

  • LEERPROTOCOOL
  • SAP
  • ICF

Deze informatie is zonder wijzigingen rechtstreeks van de website clinicaltrials.gov gehaald. Als u verzoeken heeft om uw onderzoeksgegevens te wijzigen, te verwijderen of bij te werken, neem dan contact op met register@clinicaltrials.gov. Zodra er een wijziging wordt doorgevoerd op clinicaltrials.gov, wordt deze ook automatisch bijgewerkt op onze website .

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