- ICH GCP
- Registro de ensayos clínicos de EE. UU.
- Ensayo clínico NCT01486485
Nafamostat Efficacy and Safety in Critically Ill Patients(NICE)
Circuit Survival and Efficacy for Middle Molecular-weight Solute Elimination Between Nafamostat Infusion and Heparinized Saline Priming
Acute kidney injury (AKI) is a common and serious problem in critically ill patients, and is known to be an independent risk factor for mortality. Renal replacement therapy (RRT) is the mainstay of supportive treatment of patients with severe acute kidney injury. The goal of RRT is to achieve adequate correction of uremia, electrolyte abnormalities, and volume overload while ensuring good hemodynamic tolerance. The advantages of continuous renal replacement therapy (CRRT) are increased time-averaged dialysis dose, less hemodynamic instability, and possibly, removal of high molecular weight solutes, such as inflammatory cytokines. Solute removal can occur by several different mechanisms in CRRT. For relatively small solutes, the importance of diffusion and convection is emphasized, for solutes of larger molecular weight, the importance of convection and adsorption is emphasized. The ability of a specific CRRT to remove a certain solute is determined by membrane characteristics. But actual measurements of middle molecule clearance in large clinical trials have not been available in most trials.
During CRRT, blood is conducted through an extracorporeal circuit, circuit clotting is a major problem in daily practice of CRRT, increasing blood loss, workload, and costs. Early clotting is related to bioincompatibility, critical illness, vascular access, CRRT circuit, and modality. Therefore, one major intervention to influence circuit survival is anticoagulation. However, systemic anticoagulation, usually with heparin, can produce hemorrhagic complications in patients at high risk of bleeding. To minimize the risk of bleeding, a number of alternative regimens has been proposed, however, each of those methods has its own limitations and complication. Nafamostat mesilate, a serine proteinase inhibitor, while inhibiting various clotting factors in filter circuit, is characterized by short half life resulting in little systemic anticoagulation effect. A recently developed CRRT AN69ST membrane® (Gambro Inc) is coated with a polyethylene imine (PEI, cationic biopolymer) on the membrane surface. Once adsorbed onto the membrane, heparin keeps its anticoagulant properties. Therefore CRRT has been managed without systemic administration of heparin.
The investigators will conduct a multicenter prospective randomized controlled open-label trial which compares the difference in circuit survival between between nafamostat infusion and heparinized saline priming as anticoagulation for CRRT. The primary end-point of this study is circuit survival, the time of 1st membrane exchange. The secondary end-point is clearance of small molecule (urea) and middle molecule (β2 microglobulin) at 0, 1, 6, 24h, ACT(activated coagulation time) measurements after 1hr of the CRRT, Hemorrhagic complication. This is a noninferiority trial. The aim is to demonstrate that nafamostat infusion is not inferior to the heparinized saline priming. For this purpose, at least 80 subjects (a total of 160) would be required for each group if type I error rate is 5% and type II error is 20% given 20% of drop-out rate during the study period. Block randomization will be used by means of a dedicated website.
There are still conflicting data on the effective exchange time of circuit membrane. Our study may help to improve prognosis in patients with severe AKI.
Descripción general del estudio
Estado
Condiciones
Intervención / Tratamiento
Tipo de estudio
Inscripción (Anticipado)
Fase
- Fase 3
Contactos y Ubicaciones
Estudio Contacto
- Nombre: Dong Ki Kim, MD, PhD.
- Número de teléfono: 82-2-2072-2303
- Correo electrónico: dkkim73@gmail.com
Ubicaciones de estudio
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Koyang, Corea, república de
- Reclutamiento
- National Health Insurance Corporation Ilsan Hospital
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Contacto:
- Tae Ik Chang, MD
- Número de teléfono: 82-31-900-0246
- Correo electrónico: tichang@hanmail.net
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Seongnam, Corea, república de
- Reclutamiento
- Seoul National University Bundang Hospital
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Contacto:
- Sejoong Kim, MD, PhD
- Número de teléfono: 82-11-9196-5245
- Correo electrónico: imsejoong@hanmail.net
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Seoul, Corea, república de
- Reclutamiento
- Seoul National University Hospital
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Contacto:
- Su Mi Lee
- Número de teléfono: 82-2-2072-1705
- Correo electrónico: promise131@hanmail.net
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Seoul, Corea, república de
- Reclutamiento
- Seoul National University Boramae Medical Center
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Contacto:
- Jung Pyo Lee, MD, PhD
- Número de teléfono: 82-2-870-2261
- Correo electrónico: kjwa1@medimail.co.kr
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Criterios de participación
Criterio de elegibilidad
Edades elegibles para estudiar
Acepta Voluntarios Saludables
Géneros elegibles para el estudio
Descripción
Inclusion Criteria:
- Injury stage of RIFLE criteria or more: > 2-fold increase in the serum creatinine or urine output < 0.5 mL/kg/hr for 12 hours
- Patients with any dialysis treatment before admission to the ICU or patients with end-stage renal failure and receiving dialysis
- Informed consent has been obtained.
Exclusion Criteria:
- patient age < 20 years or > 85 years
- life expectancy less than 3 months (ex. terminal stage of malignancy)
- Child-Pugh class C liver cirrhosis
- pregnancy or lactation
- history of anticoagulation prior to the randomization
- bleeding tendency (platelet count < 50,000/ul, INR > 2.5, PTT > 65, or fibrinogen < 1.00 g/L)
- history of hemorrhagic disease (ex. GI bleeding, cerebral hemorrhage, pulmonary hemorrhage)
Plan de estudios
¿Cómo está diseñado el estudio?
Detalles de diseño
- Asignación: Aleatorizado
- Modelo Intervencionista: Asignación paralela
- Enmascaramiento: Ninguno (etiqueta abierta)
Armas e Intervenciones
Grupo de participantes/brazo |
Intervención / Tratamiento |
---|---|
Experimental: heparinized saline priming group
Experimental group : heparinized saline priming group
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Comparador activo: nafamostat infusion group after heparinized saline priming
active comparator : nafamostat infusion group after heparinized saline priming
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¿Qué mide el estudio?
Medidas de resultado primarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
---|---|---|
the time of 1st membrane exchange
Periodo de tiempo: the time of 'filter is clotted'
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the time of 'filter is clotted'
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the time of 'filter is clotted'
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Medidas de resultado secundarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
---|---|---|
Clearance of small molecule (urea)
Periodo de tiempo: 0, 1, 6, 24h
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Clearance of small molecule (urea)
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0, 1, 6, 24h
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Clearance of middle molecule (β-2 microglobulin)
Periodo de tiempo: 0, 1, 6, 24h
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Clearance of middle molecule (β-2 microglobulin)
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0, 1, 6, 24h
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ACT(activated coagulation time) measurements after 1hr of the CRRT
Periodo de tiempo: after 1hr of the CRRT
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ACT(activated coagulation time) measurements after 1hr of the CRRT
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after 1hr of the CRRT
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Hemorrhagic complication
Periodo de tiempo: during CRRT
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Hemorrhagic complication
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during CRRT
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Colaboradores e Investigadores
Patrocinador
Colaboradores
Investigadores
- Silla de estudio: Dong Ki Kim, MD, PhD, Seoul National University Hospital
Publicaciones y enlaces útiles
Fechas de registro del estudio
Fechas importantes del estudio
Inicio del estudio
Finalización primaria (Anticipado)
Finalización del estudio (Anticipado)
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 (Estimar)
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
- Enfermedades Renales
- Enfermedades urológicas
- Insuficiencia renal
- Lesión renal aguda
- Efectos fisiológicos de las drogas
- Mecanismos moleculares de acción farmacológica
- Agentes del sistema nervioso periférico
- Inhibidores de enzimas
- Analgésicos
- Agentes del sistema sensorial
- Agentes antiinflamatorios no esteroideos
- Analgésicos no narcóticos
- Agentes antiinflamatorios
- Agentes antirreumáticos
- Agentes inmunosupresores
- Factores inmunológicos
- Inhibidores de la proteasa
- Inhibidores de la serina proteinasa
- Anticoagulantes
- Inhibidores de tripsina
- Agentes inactivadores del complemento
- Nafamostat
Otros números de identificación del estudio
- Nafamostat01
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