Effekter av SGLT2-hämmaren Empagliflozin hos patienter med euvolemisk och hypervolemisk hyponatremi (EMPOWER)
Effekter av SGLT2-hämmaren Empagliflozin hos patienter med euvolemisk och hypervolemisk hyponatremi - en multicentrisk randomiserad dubbelblind placebokontrollerad studie (EMPOWER-studien)
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.
Studieöversikt
Status
Betingelser
Intervention / Behandling
Studietyp
Inskrivning (Faktisk)
Fas
- Fas 4
Kontakter och platser
Studieorter
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Rotterdam, Nederländerna, 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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Würzburg, Tyskland, 97080
- University Hospital of Würzburg, med. Poliklinik
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Deltagandekriterier
Urvalskriterier
Åldrar som är berättigade till studier
Tar emot friska volontärer
Kön som är behöriga för studier
Beskrivning
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
Studieplan
Hur är studien utformad?
Designdetaljer
- Primärt syfte: Behandling
- Tilldelning: Randomiserad
- Interventionsmodell: Parallellt uppdrag
- Maskning: Fyrdubbla
Vapen och interventioner
Deltagargrupp / Arm |
Intervention / Behandling |
|---|---|
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Experimentell: 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-jämförare: Placebo
Placebo (Lactose tablet) per os once daily for 30 days |
Placebo per os once daily for 30 days |
Vad mäter studien?
Primära resultatmått
Resultatmått |
Åtgärdsbeskrivning |
Tidsram |
|---|---|---|
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Change in average daily area under curve (AUC) for serum sodium concentration
Tidsram: 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)
Tidsram: 30 days
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Absolute change in serum sodium concentration from baseline to end of treatment |
30 days
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Sekundära resultatmått
Resultatmått |
Åtgärdsbeskrivning |
Tidsram |
|---|---|---|
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Impact intervention on bodyweight
Tidsram: 30 days
|
change of bodyweight |
30 days
|
|
Impact intervention on blood pressure
Tidsram: 30 days
|
change of blood pressure |
30 days
|
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Course of serum sodium level
Tidsram: 30 days
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Course of serum sodium level |
30 days
|
|
Change of plasma osmolality
Tidsram: 30 days
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Change of plasma osmolality |
30 days
|
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Change of urinary osmolality
Tidsram: 30 days
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Change of urinary osmolality |
30 days
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|
Change of plasma urea
Tidsram: 30 days
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Change of plasma urea |
30 days
|
|
Change of urinary urea
Tidsram: 30 days
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Change of urinary urea |
30 days
|
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Change of plasma uric acid
Tidsram: 30 days
|
Change of plasma uric acid |
30 days
|
|
Change of urinary uric acid
Tidsram: 30 days
|
Change of urinary uric acid |
30 days
|
|
Change of plasma creatinin
Tidsram: 30 days
|
Change of plasma creatinin |
30 days
|
|
Change of urinary creatinin
Tidsram: 30 days
|
Change of urinary creatinin |
30 days
|
|
Change of plasma potassium
Tidsram: 30 days
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Change of plasma potassium |
30 days
|
|
Change of urinary potassium
Tidsram: 30 days
|
Change of urinary potassium |
30 days
|
|
Change in plasma copeptin
Tidsram: 30 days
|
Change in plasma copeptin |
30 days
|
|
Change in plasma aldosterone
Tidsram: 30 days
|
Change in plasma aldosterone |
30 days
|
|
Change in plasma renin
Tidsram: 30 days
|
Change in plasma renin |
30 days
|
|
Change in plasma MR-proANP
Tidsram: 30 days
|
Change in plasma MR-proANP |
30 days
|
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Change in plasma NT-proBNP
Tidsram: 30 days
|
Change in plasma NT-proBNP |
30 days
|
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Change in plasma CTX
Tidsram: 30 days
|
Change in plasma CTX |
30 days
|
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Change in plasma P1NP
Tidsram: 30 days
|
Change in plasma P1NP |
30 days
|
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Occurence of thirst
Tidsram: 30 days
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Occurence of thirst |
30 days
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Occurence of headache
Tidsram: 30 days
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Occurence of headache |
30 days
|
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Occurence of vertigo
Tidsram: 30 days
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Occurence of vertigo |
30 days
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Occurence of nausea
Tidsram: 30 days
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Occurence of nausea |
30 days
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Change in general well-being
Tidsram: 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
Tidsram: 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
Tidsram: 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
Tidsram: 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
Tidsram: 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
Tidsram: 30 days
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Change in grip strength measured with a hand dynamometer |
30 days
|
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Occurence of falls
Tidsram: 30 days
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Occurence of falls |
30 days
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Occurence of fractures
Tidsram: 30 days
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Occurence of fractures |
30 days
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Length of hospital stay
Tidsram: 30 days
|
Length of hospital stay |
30 days
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Samarbetspartners och utredare
Utredare
- Huvudutredare: Julie Refardt, MD, University Hospital, Basel, Switzerland
Studieavstämningsdatum
Studera stora datum
Studiestart (Faktisk)
Primärt slutförande (Faktisk)
Avslutad studie (Faktisk)
Studieregistreringsdatum
Först inskickad
Först inskickad som uppfyllde QC-kriterierna
Första postat (Faktisk)
Uppdateringar av studier
Senaste uppdatering publicerad (Faktisk)
Senaste inskickade uppdateringen som uppfyllde QC-kriterierna
Senast verifierad
Mer information
Termer relaterade till denna studie
Ytterligare relevanta MeSH-villkor
- Urogenitala sjukdomar
- Sjukdomar i det endokrina systemet
- Hjärnsjukdomar
- Sjukdomar i centrala nervsystemet
- Sjukdomar i nervsystemet
- Manliga urogenitala sjukdomar
- Njursjukdomar
- Urologiska sjukdomar
- Kvinnliga urogenitala sjukdomar
- Kvinnliga urogenitala sjukdomar och graviditetskomplikationer
- Metaboliska sjukdomar
- Matsmältningssystemets sjukdomar
- Leversjukdomar
- Vatten-elektrolyt obalans
- Hypothalamus sjukdomar
- Hypofyssjukdomar
- Leverinsufficiens
- Närings- och metabola sjukdomar
- Njurinsufficiens
- Leversvikt
- Hyponatremi
- Olämpligt ADH-syndrom
- empagliflozin
Andra studie-ID-nummer
- EMPOWER study
Plan för individuella deltagardata (IPD)
Planerar du att dela individuella deltagardata (IPD)?
Läkemedels- och apparatinformation, studiedokument
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