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- Ensayo clínico NCT01573806
Pharmacology of Exenatide in Pediatric Sepsis (PEPS)
3 de octubre de 2017 actualizado por: Jerry Zimmerman, Seattle Children's Hospital
Phase 1-2 Study of the Pharmacology of Exenatide in Pediatric Sepsis
Pharmacology of Exenatide in Pediatric Sepsis, PEPS is a phase 1-2 research study that will examine drug safety, drug metabolism, drug action and preliminary drug clinical effects of four does of exenatide injected every 12 hours to children with shock from infection (septic shock).
The investigators hypothesize that exenatide can be safely dosed to children with sepsis to achieve blood levels of drug similar to that achieved in teenagers with type 2 diabetes.
The investigators further hypothesize that injection of exenatide to children with septic shock will normalize blood glucose levels and decrease levels of inflammation proteins in the blood during the early course of sepsis.
Descripción general del estudio
Estado
Retirado
Condiciones
Intervención / Tratamiento
Descripción detallada
Pharmacology of Exenatide in Pediatric Sepsis, PEPS is a phase 1-2 investigation that will examine safety, pharmacokinetics, pharmacodynamics, and preliminary clinical efficacy of 4 subcutaneous doses of exenatide administered every 12 hours to children with newly diagnosed septic shock.
The investigators' long term goal is to explore the potential benefit of exenatide on: early immunomodulation and glucose homeostasis, organ dysfunction, and clinically meaningful outcomes associated with pediatric sepsis.
The current study objectives are to conduct a "3+3" dose escalation study, and then examine a "best exenatide allometric dose" to generate safety, pharmacokinetic, pharmacodynamic, and initial efficacy data in a larger cohort.
In Phase 1 (three allometric doses; three age strata)the investigators will identify an exenatide dosing regimen that mimics area under the exenatide concentration curve for exenatide dosing among adolescents with type 2 diabetes with minimal or no adverse events.
A total of 18 subjects are expected to be enrolled in Phase 1.
In Phase 2 the investigators will utilize this "best exenatide allometric dose" to further clarify exenatide safety (adverse event occurence: e.g.
nausea, abdominal pain, delayed gastric emptying, hypoglycemia, pancreatitis, renal dysfunction), pharmacokinetics, pharmacodynamics (glucose homeostasis; inflammatory cytokine serum concentrations), and effect on clinical outcomes (AUC of Saturation Index, AUC Vasoactive-Inotropic Score, AUC RIFLE Criteria, Pediatric Logistic Organ Dysfunction Score; changes in health-related quality of life and functional status).
In Phase 2, 30 subjects in each age strata in the ratio of 4:1, exenatide: vehicle, are expected to be enrolled.
Tipo de estudio
Intervencionista
Fase
- Fase 2
- Fase 1
Contactos y Ubicaciones
Esta sección proporciona los datos de contacto de quienes realizan el estudio e información sobre dónde se lleva a cabo este estudio.
Ubicaciones de estudio
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Washington
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Seattle, Washington, Estados Unidos, 98105
- Seattle Children's Hospital
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Criterios de participación
Los investigadores buscan personas que se ajusten a una determinada descripción, denominada criterio de elegibilidad. Algunos ejemplos de estos criterios son el estado de salud general de una persona o tratamientos previos.
Criterio de elegibilidad
Edades elegibles para estudiar
1 mes a 18 años (Niño, Adulto)
Acepta Voluntarios Saludables
No
Géneros elegibles para el estudio
Todos
Descripción
Inclusion Criteria:
- Age 44 weeks estimated gestational age to 18 years AND
- Admitted to the PICU for the sepsis event AND
- Vascular catheter capable of providing serial blood samples in place AND
- Diagnosis of septic shock = sepsis with cardiovascular organ dysfunction AND
- Parents speak English or Spanish
Exclusion Criteria:
- Greater than 12 hours from admission to PICU to enrollment OR
- Chronic or acute dialytic therapy, history of renal impairment or renal transplantation OR
- History of pancreatitis OR
- History of hypersensitivity to Byetta OR
- History of severe gastrointestinal disease or gastroparesis OR
- History of diabetes mellitus, type I or type II OR
- History of insulin, sulfonyl urea drugs, or coumarin use OR
- History of hypoglycemia OR
- History of active pregnancy (effect of exenatide on the fetus is unknown) OR
- Inability to collect serial blood samples OR
- Previously enrolled in the PEPS study OR
- Lack of commitment to aggressive sepsis therapy OR
- Expectation to succumb from the sepsis event OR
- Patient is a foster child and/or ward of the state OR
- Sepsis event associated with a PICU-acquired nosocomial infection OR
- Patient is enrolled in another interventional investigation that might obscure the potential effects of exenatide dosing.
Plan de estudios
Esta sección proporciona detalles del plan de estudio, incluido cómo está diseñado el estudio y qué mide el estudio.
¿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 |
---|---|
Comparador activo: Exenatide
Subjects dosed with exenatide in Phase 2
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Exenatide, dosed subcutaneously every 12 hours for 4 doses
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Comparador de placebos: Exenatide vehicle
Subjects dosed with exenatide vehicle in Phase 2
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Exenatide vehicle, dosed subcutaneously every 12 hours for 4 doses
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¿Qué mide el estudio?
Medidas de resultado primarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
---|---|---|
Exenatide associated adverse event occurence
Periodo de tiempo: From PICU admission to PICU discharge, an average interval of 7.5 days
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Potential adverse events associated with exenatide: nausea, abdominal pain, hypoglycemia, delayed gastric emptying, pancreatitis, renal dysfunction, reactions at injection site.
Adverse event occurence will be tabulated while the subject remains in the PICU.
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From PICU admission to PICU discharge, an average interval of 7.5 days
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Exenatide pharmacokinetics: Area under the exenatide concentration curve for 4 subcutaneous exenatide injections administered every 12 hours.
Periodo de tiempo: 48 hours following the first exenatide dose
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Delineation of the pharmacokinetics of subcutaneously dosed exenatide among children with de novo septic shock.
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48 hours following the first exenatide dose
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Medidas de resultado secundarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
---|---|---|
Exenatide pharmacodynamics: Effect of exenatide on glucose homeostasis
Periodo de tiempo: 60 hours following first exenatide dose
|
Delineation of exenatide pharmacodynamics among children with de novo septic shock: AUC of all serum glucose values or results of continuous glucose monitoring obtained during the 60 hours following the first dose of exenatide (or drug vehicle).
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60 hours following first exenatide dose
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Exenatide pharmacodynamics: Effect of exenatide on serum inflammatory cytokine concentrations.
Periodo de tiempo: 60 hours following first exenatide dose
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Delineation of exenatide pharmacodynamics among children with de novo septic shock: AUC of serial serum inflammatory cytokine concentrations.
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60 hours following first exenatide dose
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Exenatide clinical efficacy: Effect of exenatide on intensity and duration of organ dysfunctions.
Periodo de tiempo: From PICU admission to PICU discharge, an average interval of 7.5 days
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AUC of daily Pediatric Logistic Organ Dysfunction (PELOD) scores while the subject remains in the PICU
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From PICU admission to PICU discharge, an average interval of 7.5 days
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Exenatide clinical efficacy: Effect of exenatide on intensity and duration of hemodynamic instability.
Periodo de tiempo: From onset to discontinuation of vasoactive-inotropic support, an average interval of 4 days
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AUC of daily Vasoactive-Inotropic Scores while the subject remains on vasoactive-inotropic support.
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From onset to discontinuation of vasoactive-inotropic support, an average interval of 4 days
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Exenatide clinical efficacy: Effect of exenatide on intensity and duration of pulmonary failure.
Periodo de tiempo: From onset to discontinuation of mechanical ventilator support, an average interval of 4.5 days
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AUC of daily Saturation Indices ([FiO2*MAP]/SpO2)
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From onset to discontinuation of mechanical ventilator support, an average interval of 4.5 days
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Exenatide clinical efficacy: Effect of exenatide on intensity and duration of renal failure
Periodo de tiempo: From PICU admission to PICU discharge, an average interval of 7.5 days
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AUC of daily RIFLE criteria
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From PICU admission to PICU discharge, an average interval of 7.5 days
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Exenatide clinical efficacy: Effect of exenatide on magnitude of sepsis-associated change in functional status.
Periodo de tiempo: 2 measurements: baseline and PICU discharge, the latter occuring on average at 7.5 days
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Determination per parent report of declination from baseline to PICU discharge of, Pediatric Overall Performance Category Score and Functional Status Score
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2 measurements: baseline and PICU discharge, the latter occuring on average at 7.5 days
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Exenatide clinical efficacy: Effect of exenatide on magnitude of sepsis-associated change in health-related quality of life
Periodo de tiempo: 2 measurements: baseline and PICU discharge, the latter occuring on average at 7.5 days
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Determination per parent report of declination from baseline to PICU discharge of, Pediatric Quality of Life Inventory, Generic Core Scales, 4.0 (PedsQL)
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2 measurements: baseline and PICU discharge, the latter occuring on average at 7.5 days
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Colaboradores e Investigadores
Aquí es donde encontrará personas y organizaciones involucradas en este estudio.
Patrocinador
Publicaciones y enlaces útiles
La persona responsable de ingresar información sobre el estudio proporciona voluntariamente estas publicaciones. Estos pueden ser sobre cualquier cosa relacionada con el estudio.
Publicaciones Generales
- Ivy SP, Siu LL, Garrett-Mayer E, Rubinstein L. Approaches to phase 1 clinical trial design focused on safety, efficiency, and selected patient populations: a report from the clinical trial design task force of the national cancer institute investigational drug steering committee. Clin Cancer Res. 2010 Mar 15;16(6):1726-36. doi: 10.1158/1078-0432.CCR-09-1961. Epub 2010 Mar 9.
- Mecott GA, Herndon DN, Kulp GA, Brooks NC, Al-Mousawi AM, Kraft R, Rivero HG, Williams FN, Branski LK, Jeschke MG. The use of exenatide in severely burned pediatric patients. Crit Care. 2010;14(4):R153. doi: 10.1186/cc9222. Epub 2010 Aug 11.
- Malloy J, Capparelli E, Gottschalk M, Guan X, Kothare P, Fineman M. Pharmacology and tolerability of a single dose of exenatide in adolescent patients with type 2 diabetes mellitus being treated with metformin: a randomized, placebo-controlled, single-blind, dose-escalation, crossover study. Clin Ther. 2009 Apr;31(4):806-15. doi: 10.1016/j.clinthera.2009.04.005.
- Deane AM, Chapman MJ, Fraser RJ, Summers MJ, Zaknic AV, Storey JP, Jones KL, Rayner CK, Horowitz M. Effects of exogenous glucagon-like peptide-1 on gastric emptying and glucose absorption in the critically ill: relationship to glycemia. Crit Care Med. 2010 May;38(5):1261-9. doi: 10.1097/CCM.0b013e3181d9d87a.
Fechas de registro del estudio
Estas fechas rastrean el progreso del registro del estudio y los envíos de resultados resumidos a ClinicalTrials.gov. Los registros del estudio y los resultados informados son revisados por la Biblioteca Nacional de Medicina (NLM) para asegurarse de que cumplan con los estándares de control de calidad específicos antes de publicarlos en el sitio web público.
Fechas importantes del estudio
Inicio del estudio
1 de octubre de 2012
Finalización primaria (Anticipado)
1 de octubre de 2014
Finalización del estudio (Anticipado)
1 de octubre de 2014
Fechas de registro del estudio
Enviado por primera vez
28 de marzo de 2012
Primero enviado que cumplió con los criterios de control de calidad
5 de abril de 2012
Publicado por primera vez (Estimar)
10 de abril de 2012
Actualizaciones de registros de estudio
Última actualización publicada (Actual)
5 de octubre de 2017
Última actualización enviada que cumplió con los criterios de control de calidad
3 de octubre de 2017
Última verificación
1 de octubre de 2017
Más información
Términos relacionados con este estudio
Palabras clave
Términos MeSH relevantes adicionales
Otros números de identificación del estudio
- PEPS-SCH-001
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. .