Wirkungen des SGLT2-Inhibitors Empagliflozin bei Patienten mit euvolämischer und hypervolämischer Hyponatriämie (EMPOWER)
Wirkungen des SGLT2-Inhibitors Empagliflozin bei Patienten mit euvolämischer und hypervolämischer Hyponatriämie – eine multizentrische, randomisierte, doppelblinde, placebokontrollierte Studie (die EMPOWER-Studie)
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.
Studienübersicht
Status
Bedingungen
Intervention / Behandlung
Studientyp
Einschreibung (Tatsächlich)
Phase
- Phase 4
Kontakte und Standorte
Studienorte
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Würzburg, Deutschland, 97080
- University Hospital of Würzburg, med. Poliklinik
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Rotterdam, Niederlande, 3015
- Erasmus Universität Medisch Centrum Rotterdam, Department of Internal Medicine
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Basel, Schweiz, 4031
- University Hospital Basel
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Biel, Schweiz, 2502
- Spitalzentrum Biel
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Canton of Lucerne
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Lucerne, Canton of Lucerne, Schweiz, 6000
- Kantonsspital Luzern
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Canton of Vaud
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Lausanne, Canton of Vaud, Schweiz, 1011
- Centre Hospitalier Universitaire Vaudois (CHUV)
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Teilnahmekriterien
Zulassungskriterien
Studienberechtigtes Alter
Akzeptiert gesunde Freiwillige
Studienberechtigte Geschlechter
Beschreibung
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
Studienplan
Wie ist die Studie aufgebaut?
Designdetails
- Hauptzweck: Behandlung
- Zuteilung: Zufällig
- Interventionsmodell: Parallele Zuordnung
- Maskierung: Vervierfachen
Waffen und Interventionen
Teilnehmergruppe / Arm |
Intervention / Behandlung |
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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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Placebo-Komparator: Placebo
Placebo (Lactose tablet) per os once daily for 30 days |
Placebo per os once daily for 30 days |
Was misst die Studie?
Primäre Ergebnismessungen
Ergebnis Maßnahme |
Maßnahmenbeschreibung |
Zeitfenster |
|---|---|---|
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Change in average daily area under curve (AUC) for serum sodium concentration
Zeitfenster: 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)
Zeitfenster: 30 days
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Absolute change in serum sodium concentration from baseline to end of treatment |
30 days
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Sekundäre Ergebnismessungen
Ergebnis Maßnahme |
Maßnahmenbeschreibung |
Zeitfenster |
|---|---|---|
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Impact intervention on bodyweight
Zeitfenster: 30 days
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change of bodyweight |
30 days
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Impact intervention on blood pressure
Zeitfenster: 30 days
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change of blood pressure |
30 days
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Course of serum sodium level
Zeitfenster: 30 days
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Course of serum sodium level |
30 days
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Change of plasma osmolality
Zeitfenster: 30 days
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Change of plasma osmolality |
30 days
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Change of urinary osmolality
Zeitfenster: 30 days
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Change of urinary osmolality |
30 days
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Change of plasma urea
Zeitfenster: 30 days
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Change of plasma urea |
30 days
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Change of urinary urea
Zeitfenster: 30 days
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Change of urinary urea |
30 days
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Change of plasma uric acid
Zeitfenster: 30 days
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Change of plasma uric acid |
30 days
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Change of urinary uric acid
Zeitfenster: 30 days
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Change of urinary uric acid |
30 days
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Change of plasma creatinin
Zeitfenster: 30 days
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Change of plasma creatinin |
30 days
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Change of urinary creatinin
Zeitfenster: 30 days
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Change of urinary creatinin |
30 days
|
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Change of plasma potassium
Zeitfenster: 30 days
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Change of plasma potassium |
30 days
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Change of urinary potassium
Zeitfenster: 30 days
|
Change of urinary potassium |
30 days
|
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Change in plasma copeptin
Zeitfenster: 30 days
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Change in plasma copeptin |
30 days
|
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Change in plasma aldosterone
Zeitfenster: 30 days
|
Change in plasma aldosterone |
30 days
|
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Change in plasma renin
Zeitfenster: 30 days
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Change in plasma renin |
30 days
|
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Change in plasma MR-proANP
Zeitfenster: 30 days
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Change in plasma MR-proANP |
30 days
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Change in plasma NT-proBNP
Zeitfenster: 30 days
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Change in plasma NT-proBNP |
30 days
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Change in plasma CTX
Zeitfenster: 30 days
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Change in plasma CTX |
30 days
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Change in plasma P1NP
Zeitfenster: 30 days
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Change in plasma P1NP |
30 days
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Occurence of thirst
Zeitfenster: 30 days
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Occurence of thirst |
30 days
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Occurence of headache
Zeitfenster: 30 days
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Occurence of headache |
30 days
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Occurence of vertigo
Zeitfenster: 30 days
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Occurence of vertigo |
30 days
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Occurence of nausea
Zeitfenster: 30 days
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Occurence of nausea |
30 days
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Change in general well-being
Zeitfenster: 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
Zeitfenster: 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
Zeitfenster: 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
Zeitfenster: 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
Zeitfenster: 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
Zeitfenster: 30 days
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Change in grip strength measured with a hand dynamometer |
30 days
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Occurence of falls
Zeitfenster: 30 days
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Occurence of falls |
30 days
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Occurence of fractures
Zeitfenster: 30 days
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Occurence of fractures |
30 days
|
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Length of hospital stay
Zeitfenster: 30 days
|
Length of hospital stay |
30 days
|
Mitarbeiter und Ermittler
Ermittler
- Hauptermittler: Julie Refardt, MD, University Hospital, Basel, Switzerland
Studienaufzeichnungsdaten
Haupttermine studieren
Studienbeginn (Tatsächlich)
Primärer Abschluss (Tatsächlich)
Studienabschluss (Tatsächlich)
Studienanmeldedaten
Zuerst eingereicht
Zuerst eingereicht, das die QC-Kriterien erfüllt hat
Zuerst gepostet (Tatsächlich)
Studienaufzeichnungsaktualisierungen
Letztes Update gepostet (Tatsächlich)
Letztes eingereichtes Update, das die QC-Kriterien erfüllt
Zuletzt verifiziert
Mehr Informationen
Begriffe im Zusammenhang mit dieser Studie
Zusätzliche relevante MeSH-Bedingungen
- Urogenitale Erkrankungen
- Erkrankungen des endokrinen Systems
- Erkrankungen des Gehirns
- Erkrankungen des zentralen Nervensystems
- Erkrankungen des Nervensystems
- Männliche Urogenitalerkrankungen
- Nierenerkrankungen
- Urologische Erkrankungen
- Weibliche Urogenitalerkrankungen
- Weibliche Urogenitalerkrankungen und Schwangerschaftskomplikationen
- Stoffwechselerkrankungen
- Erkrankungen des Verdauungssystems
- Leberkrankheiten
- Wasser-Elektrolyt-Ungleichgewicht
- Hypothalamische Erkrankungen
- Hypophysenerkrankungen
- Leberinsuffizienz
- Ernährungs- und Stoffwechselerkrankungen
- Niereninsuffizienz
- Leberversagen
- Hyponatriämie
- Unangemessenes ADH-Syndrom
- Empagliflozin
Andere Studien-ID-Nummern
- EMPOWER study
Plan für individuelle Teilnehmerdaten (IPD)
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