Efectos del inhibidor de SGLT2 empagliflozina en pacientes con hiponatremia euvolémica e hipervolémica (EMPOWER)
Efectos del inhibidor de SGLT2 Empagliflozin en pacientes con hiponatremia euvolémica e hipervolémica: un ensayo multicéntrico, aleatorizado, doble ciego, controlado con placebo (estudio EMPOWER)
Hyponatremia is the most common electrolyte derangement occurring in hospitalized patients. It is usually classified as hypovolemic, euvolemic or hypervolemic. The most common aetiology of euvolemic hyponatremia is the syndrome of inappropriate antidiuresis (SIAD). Hypervolemic hyponatremia is common in patients with congestive heart failure (CHF) (10-27%) and liver cirrhosis (up to approximately 50%). In SIAD, the regulation of arginine vasopressin (AVP) secretion is impaired which leads to free water retention. In CHF and liver cirrhosis, the effective arterial blood volume is decreased leading to non-osmotic baroreceptor mediated AVP release and consecutive free water retention.
Current treatments of euvolemic and hypervolemic hyponatremia, including the most used treatment fluid restriction, are of limited efficacy. Sodium-Glucose-Co-Transporter 2 (SGLT2) inhibitors reduce glucose reabsorption in the proximal tubule, resulting in glucosuria and consecutive osmotic diuresis. A placebo-controlled randomized trial of our group has shown that a short-term, i.e. a 4-days administration of the SGLT2 inhibitor empagliflozin (Jardiance)® in addition to fluid restriction was effective in increasing the serum sodium concentration in 87 patients with SIAD-induced hyponatremia. The effect of empagliflozin (Jardiance)® without additional fluid restriction is however not yet known. Large randomized controlled trials have shown that SGLT2 inhibitors reduced hospitalization for heart failure in patients with, and more recently without type 2 diabetes. No studies have investigated the effect of SGLT2 inhibitors in hypervolemic hyponatremia.
To evaluate the effect of empagliflozin (Jardiance)® in eu- and hypervolemic hyponatremia, a randomized placebo-controlled study is needed.
Descripción general del estudio
Estado
Condiciones
Intervención / Tratamiento
Tipo de estudio
Inscripción (Actual)
Fase
- Fase 4
Contactos y Ubicaciones
Ubicaciones de estudio
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Würzburg, Alemania, 97080
- University Hospital of Würzburg, med. Poliklinik
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Rotterdam, Países Bajos, 3015
- Erasmus Universität Medisch Centrum Rotterdam, Department of Internal Medicine
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Basel, Suiza, 4031
- University Hospital Basel
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Biel, Suiza, 2502
- Spitalzentrum Biel
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Canton of Lucerne
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Lucerne, Canton of Lucerne, Suiza, 6000
- Kantonsspital Luzern
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Canton of Vaud
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Lausanne, Canton of Vaud, Suiza, 1011
- Centre Hospitalier Universitaire Vaudois (CHUV)
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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:
- chronic eu- OR hypervolemic non hyperosmolar (<300 mOsm/kg) hyponatremia (heparin plasma sodium <135 mmol/L on day of inclusion)
Exclusion Criteria:
- known hypersensitivity or allergy to class of drugs or the investigational product,
- severe symptomatic hyponatremia in need of treatment with 3% NaCl-solution or in need of intensive/intermediate care treatment at time of inclusion
- clinical hypovolemia
- Severe reduction of eGFR <20 mL/min/1,73 m2 (KDIGO G4 and G5) or end stage renal disease
- Chronic liver insufficiency with Child Pugh Score ≥10 or decompensated liver cirrhosis (jaundice, hepatorenal syndrome, encephalopathy, bleeding, …)
- Hepatic impairment defined as aspartate transaminase (AST) or alanine transaminase (ALT) >3x the upper limit of normal (ULN); or total bilirubin >2x ULN at time of enrolment
- uncontrolled hypothyroidism
- uncontrolled adrenal insufficiency
- systolic blood pressure <90mmHg
- contraindication for lowering blood pressure
- diabetes mellitus type 1 or pancreatic diabetes mellitus
- treatment with SGLT2 inhibitors, lithium chloride, vaptans, demeclocycline or urea on inclusion day
- severe immunosuppression (leucocytes <2 G/l)
- peripheral arterial disease stage III-IV of the Fontaine Classification
- fasting or other reasons preventing medication intake
- previous enrolment into the current study
- participation in another intervention study
- pregnancy, breastfeeding, intention to become pregnant during the course of the study or lack of safe contraception.
- end of life care
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 |
|---|---|
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Experimental: Empagliflozin
Empagliflozin (Jardiance)® 25mg per os once daily for 30 days |
Empagliflozin 25mg per os once daily for 30 days |
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Comparador de placebos: Placebo
Placebo (Lactose tablet) per os once daily for 30 days |
Placebo per os once daily for 30 days |
¿Qué mide el estudio?
Medidas de resultado primarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
|---|---|---|
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Change in average daily area under curve (AUC) for serum sodium concentration
Periodo de tiempo: 4 days
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Change in average daily AUC for serum sodium concentration |
4 days
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Long-term serum sodium change (before/after treatment)
Periodo de tiempo: 30 days
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Absolute change in serum sodium concentration from baseline to end of treatment |
30 days
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Medidas de resultado secundarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
|---|---|---|
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Impact intervention on bodyweight
Periodo de tiempo: 30 days
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change of bodyweight |
30 days
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Impact intervention on blood pressure
Periodo de tiempo: 30 days
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change of blood pressure |
30 days
|
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Course of serum sodium level
Periodo de tiempo: 30 days
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Course of serum sodium level |
30 days
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Change of plasma osmolality
Periodo de tiempo: 30 days
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Change of plasma osmolality |
30 days
|
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Change of urinary osmolality
Periodo de tiempo: 30 days
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Change of urinary osmolality |
30 days
|
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Change of plasma urea
Periodo de tiempo: 30 days
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Change of plasma urea |
30 days
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Change of urinary urea
Periodo de tiempo: 30 days
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Change of urinary urea |
30 days
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Change of plasma uric acid
Periodo de tiempo: 30 days
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Change of plasma uric acid |
30 days
|
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Change of urinary uric acid
Periodo de tiempo: 30 days
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Change of urinary uric acid |
30 days
|
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Change of plasma creatinin
Periodo de tiempo: 30 days
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Change of plasma creatinin |
30 days
|
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Change of urinary creatinin
Periodo de tiempo: 30 days
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Change of urinary creatinin |
30 days
|
|
Change of plasma potassium
Periodo de tiempo: 30 days
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Change of plasma potassium |
30 days
|
|
Change of urinary potassium
Periodo de tiempo: 30 days
|
Change of urinary potassium |
30 days
|
|
Change in plasma copeptin
Periodo de tiempo: 30 days
|
Change in plasma copeptin |
30 days
|
|
Change in plasma aldosterone
Periodo de tiempo: 30 days
|
Change in plasma aldosterone |
30 days
|
|
Change in plasma renin
Periodo de tiempo: 30 days
|
Change in plasma renin |
30 days
|
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Change in plasma MR-proANP
Periodo de tiempo: 30 days
|
Change in plasma MR-proANP |
30 days
|
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Change in plasma NT-proBNP
Periodo de tiempo: 30 days
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Change in plasma NT-proBNP |
30 days
|
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Change in plasma CTX
Periodo de tiempo: 30 days
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Change in plasma CTX |
30 days
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Change in plasma P1NP
Periodo de tiempo: 30 days
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Change in plasma P1NP |
30 days
|
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Occurence of thirst
Periodo de tiempo: 30 days
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Occurence of thirst |
30 days
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Occurence of headache
Periodo de tiempo: 30 days
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Occurence of headache |
30 days
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Occurence of vertigo
Periodo de tiempo: 30 days
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Occurence of vertigo |
30 days
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Occurence of nausea
Periodo de tiempo: 30 days
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Occurence of nausea |
30 days
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Change in general well-being
Periodo de tiempo: 30 days
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Change in general well-being according to visual analogue scale |
30 days
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Change in quality of life
Periodo de tiempo: 30 days
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change in quality of life according to EQ-5D-5L questionnaire |
30 days
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Change in cognitive impairment
Periodo de tiempo: 30 days
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Change in cognitive impairment measured with the MoCa test |
30 days
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Change in visual attention
Periodo de tiempo: 30 days
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Change in visual attention measured with the trail making test |
30 days
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Change in neuromuscular impairment
Periodo de tiempo: 30 days
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Change in neuromuscular impairment measured with the timed up and go test |
30 days
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Change in grip strength
Periodo de tiempo: 30 days
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Change in grip strength measured with a hand dynamometer |
30 days
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Occurence of falls
Periodo de tiempo: 30 days
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Occurence of falls |
30 days
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Occurence of fractures
Periodo de tiempo: 30 days
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Occurence of fractures |
30 days
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Length of hospital stay
Periodo de tiempo: 30 days
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Length of hospital stay |
30 days
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Colaboradores e Investigadores
Patrocinador
Investigadores
- Investigador principal: Julie Refardt, MD, University Hospital, Basel, Switzerland
Fechas de registro del estudio
Fechas importantes del estudio
Inicio del estudio (Actual)
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 (Actual)
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
Términos MeSH relevantes adicionales
- Enfermedades urogenitales
- Enfermedades del sistema endocrino
- Enfermedades Cerebrales
- Enfermedades del Sistema Nervioso Central
- Enfermedades del Sistema Nervioso
- Enfermedades urogenitales masculinas
- Enfermedades Renales
- Enfermedades urológicas
- Enfermedades urogenitales femeninas
- Enfermedades urogenitales femeninas y complicaciones del embarazo
- Enfermedades metabólicas
- Enfermedades del Sistema Digestivo
- Enfermedades del HIGADO
- Desequilibrio de agua y electrolitos
- Enfermedades hipotalámicas
- Enfermedades de la pituitaria
- Insuficiencia hepática
- Enfermedades Nutricionales y Metabólicas
- Insuficiencia renal
- Insuficiencia hepática
- Hiponatremia
- Síndrome de ADH inadecuada
- empagliflozin
Otros números de identificación del estudio
- EMPOWER study
Plan de datos de participantes individuales (IPD)
¿Planea compartir datos de participantes individuales (IPD)?
Información sobre medicamentos y dispositivos, documentos del estudio
Estudia un producto farmacéutico regulado por la FDA de EE. UU.
Estudia un producto de dispositivo regulado por la FDA de EE. UU.
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