- ICH GCP
- Registro de ensayos clínicos de EE. UU.
- Ensayo clínico NCT01452789
Blinded Trial of Buprenorphine or Morphine in the Treatment of the Neonatal Abstinence Syndrome
A Randomized, Active-Control, Double-Blind, Double-Dummy Clinical Trial Comparing Sublingual Buprenorphine And Morphine Solution For The Treatment Of Neonatal Opioid Abstinence Syndrome
Descripción general del estudio
Estado
Condiciones
Intervención / Tratamiento
Descripción detallada
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).
Tipo de estudio
Inscripción (Actual)
Fase
- Fase 3
Contactos y Ubicaciones
Ubicaciones de estudio
-
-
Pennsylvania
-
Philadelphia, Pennsylvania, Estados Unidos, 19107
- Thomas Jefferson University Hosptial
-
-
Criterios de participación
Criterio de elegibilidad
Edades elegibles para estudiar
- Niño
- Adulto
- Adulto Mayor
Acepta Voluntarios Saludables
Géneros elegibles para el estudio
Descripción
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
Plan de estudios
¿Cómo está diseñado el estudio?
Detalles de diseño
- Propósito principal: Tratamiento
- Asignación: Aleatorizado
- Modelo Intervencionista: Asignación paralela
- Enmascaramiento: Cuadruplicar
Armas e Intervenciones
Grupo de participantes/brazo |
Intervención / Tratamiento |
---|---|
Experimental: sublingual buprenorphine
This is the group that received active sublingual buprenorphine and placebo for oral morphine
|
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
Otros nombres:
|
Comparador activo: oral morphine
This is the group that received active oral morphine and placebo for sublingual buprenorphine
|
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
|
¿Qué mide el estudio?
Medidas de resultado primarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
---|---|---|
Length of Treatment
Periodo de tiempo: 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.
|
Medidas de resultado secundarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
---|---|---|
Length of Hospitalization
Periodo de tiempo: 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.
Periodo de tiempo: 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
Periodo de tiempo: 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.
|
Colaboradores e Investigadores
Patrocinador
Colaboradores
Investigadores
- Investigador principal: Walter K Kraft, MD, Thomas Jeffeson University
Publicaciones y enlaces útiles
Publicaciones Generales
- 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.
- 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.
- 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.
- 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.
Fechas de registro del estudio
Fechas importantes del estudio
Inicio del estudio
Finalización primaria (Actual)
Finalización del estudio (Actual)
Fechas de registro del estudio
Enviado por primera vez
Primero enviado que cumplió con los criterios de control de calidad
Publicado por primera vez (Estimar)
Actualizaciones de registros de estudio
Última actualización publicada (Actual)
Última actualización enviada que cumplió con los criterios de control de calidad
Última verificación
Más información
Términos relacionados con este estudio
Palabras clave
Términos MeSH relevantes adicionales
- Desordenes mentales
- Trastornos inducidos químicamente
- Procesos Patológicos
- Trastornos relacionados con sustancias
- Enfermedad
- Infantil, Recién Nacido, Enfermedades
- Síndrome
- Síndrome de Abstinencia Neonatal
- Efectos fisiológicos de las drogas
- Depresores del sistema nervioso central
- Agentes del sistema nervioso periférico
- Analgésicos
- Agentes del sistema sensorial
- Analgésicos Opiáceos
- Estupefacientes
- Antagonistas de narcóticos
- Buprenorfina
- Morfina
Otros números de identificación del estudio
- 11F.193
- R01DA029076-01A1 (Subvención/contrato del NIH de EE. UU.)
Plan de datos de participantes individuales (IPD)
¿Planea compartir datos de participantes individuales (IPD)?
Descripción del plan IPD
Marco de tiempo para compartir IPD
Criterios de acceso compartido de IPD
Tipo de información de apoyo para compartir IPD
- PROTOCOLO DE ESTUDIO
- SAVIA
- CIF
Esta información se obtuvo directamente del sitio web clinicaltrials.gov sin cambios. Si tiene alguna solicitud para cambiar, eliminar o actualizar los detalles de su estudio, comuníquese con register@clinicaltrials.gov. Tan pronto como se implemente un cambio en clinicaltrials.gov, también se actualizará automáticamente en nuestro sitio web. .
Ensayos clínicos sobre Síndrome de Abstinencia Neonatal
-
University of AarhusTerminadoHiperbilirrubinemia Neonatal No ComplicadaDinamarca
-
Guangzhou Women and Children's Medical CenterReclutamientoHiperbilirrubinemia neonatal | Ictericia neonatal | Hemólisis NeonatalPorcelana
-
HonorHealth Research InstituteNeolightTerminadoHiperbilirrubinemia neonatal | Ictericia Neonatal | Trastorno neonatalEstados Unidos
-
Muhammad ZarkAún no reclutandoIctericia neonatal fisiológica | Hiperbilirrubinemia fisiológicaPakistán
-
Jip GroenInBiomeReclutamientoColonización Microbiana | Infeccion Neonatal | Sepsis Neonatal, Inicio Temprano | Enfermedad microbiana | Sepsis clínica | Sepsis neonatal con cultivo negativo | Sepsis Neonatal, Inicio Tardío | Sepsis neonatal con cultivo positivoPaíses Bajos
-
University College, LondonMinistry of Health and Child Welfare, Zimbabwe; Biomedical Research and Training... y otros colaboradoresReclutamientoEncefalopatía Neonatal | Precocidad | Convulsión Neonatal | Ictericia neonatal | Sepsis neonatal | Muerte Neonatal | Insuficiencia respiratoria neonatal | Hipoglucemia neonatal | Trastorno neonatal | Hipotermia NeonatalZimbabue, Malaui
-
National Liver Institute, EgyptTerminadoIctericia neonatalEgipto
-
Wollo UniversityJimma UniversityReclutamientoAtención NeonatalEtiopía
-
The Hospital for Sick ChildrenAga Khan University; Grand Challenges Canada; March of Dimes; UBS Optimus Foundation y otros colaboradoresTerminado
-
Ege UniversityAssociate Professor Figen YARDIMCIAún no reclutandoIctericia fetal y neonatal no especificada
Ensayos clínicos sobre sublingual buprenorphine
-
Stallergenes GreerTerminadoEnfermedad primariaFrancia, Italia, España
-
Inmunotek S.L.TerminadoRinitis | RinoconjuntivitisEspaña
-
Stallergenes GreerTerminadoRinitis alérgica por pólenes de gramíneasEstados Unidos
-
Bispebjerg HospitalLund University; University of Copenhagen; ALK-Abelló A/STerminadoAsma alérgica por Dermatophagoides PteronyssinusDinamarca
-
Medical University of LodzDesconocidoRinitis alérgica | Asma bronquialPolonia
-
Inmunotek S.L.DesconocidoRinitis | RinoconjuntivitisEspaña
-
HAL AllergyTerminadoAlergia al polen de abedul | Rinitis Estacional y/o RinoconjuntivitisAlemania
-
Zagazig UniversityAún no reclutando
-
Zagazig UniversityTerminadoEfectos de la inmunoterapiaEgipto
-
ALK-Abelló A/SActivo, no reclutandoRinitis alérgica por Dermatophagoides Farinae | Rinitis alérgica por Dermatophagoides Pteronyssinus | Rinitis alérgica por ácaros del polvo domésticoEspaña, Federación Rusa, Estados Unidos, Polonia, Bulgaria, Canadá, Francia, Alemania, Lituania, Eslovaquia, Ucrania