Virkninger af SGLT2-hæmmeren Empagliflozin hos patienter med euvolæmisk og hypervolæmisk hyponatriæmi (EMPOWER)
Virkninger af SGLT2-hæmmeren Empagliflozin hos patienter med euvolæmisk og hypervolæmisk hyponatriæmi - et multicentrisk randomiseret dobbeltblindt placebokontrolleret forsøg (EMPOWER-undersøgelsen)
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.
Studieoversigt
Status
Betingelser
Intervention / Behandling
Undersøgelsestype
Tilmelding (Faktiske)
Fase
- Fase 4
Kontakter og lokationer
Studiesteder
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Rotterdam, Holland, 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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Deltagelseskriterier
Berettigelseskriterier
Aldre berettiget til at studere
Tager imod sunde frivillige
Køn, der er berettiget til at studere
Beskrivelse
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
Hvordan er undersøgelsen tilrettelagt?
Design detaljer
- Primært formål: Behandling
- Tildeling: Randomiseret
- Interventionel model: Parallel tildeling
- Maskning: Firedobbelt
Våben og indgreb
Deltagergruppe / Arm |
Intervention / Behandling |
|---|---|
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Eksperimentel: 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 |
Hvad måler undersøgelsen?
Primære resultatmål
Resultatmål |
Foranstaltningsbeskrivelse |
Tidsramme |
|---|---|---|
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Change in average daily area under curve (AUC) for serum sodium concentration
Tidsramme: 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)
Tidsramme: 30 days
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Absolute change in serum sodium concentration from baseline to end of treatment |
30 days
|
Sekundære resultatmål
Resultatmål |
Foranstaltningsbeskrivelse |
Tidsramme |
|---|---|---|
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Impact intervention on bodyweight
Tidsramme: 30 days
|
change of bodyweight |
30 days
|
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Impact intervention on blood pressure
Tidsramme: 30 days
|
change of blood pressure |
30 days
|
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Course of serum sodium level
Tidsramme: 30 days
|
Course of serum sodium level |
30 days
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Change of plasma osmolality
Tidsramme: 30 days
|
Change of plasma osmolality |
30 days
|
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Change of urinary osmolality
Tidsramme: 30 days
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Change of urinary osmolality |
30 days
|
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Change of plasma urea
Tidsramme: 30 days
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Change of plasma urea |
30 days
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Change of urinary urea
Tidsramme: 30 days
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Change of urinary urea |
30 days
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Change of plasma uric acid
Tidsramme: 30 days
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Change of plasma uric acid |
30 days
|
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Change of urinary uric acid
Tidsramme: 30 days
|
Change of urinary uric acid |
30 days
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Change of plasma creatinin
Tidsramme: 30 days
|
Change of plasma creatinin |
30 days
|
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Change of urinary creatinin
Tidsramme: 30 days
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Change of urinary creatinin |
30 days
|
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Change of plasma potassium
Tidsramme: 30 days
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Change of plasma potassium |
30 days
|
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Change of urinary potassium
Tidsramme: 30 days
|
Change of urinary potassium |
30 days
|
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Change in plasma copeptin
Tidsramme: 30 days
|
Change in plasma copeptin |
30 days
|
|
Change in plasma aldosterone
Tidsramme: 30 days
|
Change in plasma aldosterone |
30 days
|
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Change in plasma renin
Tidsramme: 30 days
|
Change in plasma renin |
30 days
|
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Change in plasma MR-proANP
Tidsramme: 30 days
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Change in plasma MR-proANP |
30 days
|
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Change in plasma NT-proBNP
Tidsramme: 30 days
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Change in plasma NT-proBNP |
30 days
|
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Change in plasma CTX
Tidsramme: 30 days
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Change in plasma CTX |
30 days
|
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Change in plasma P1NP
Tidsramme: 30 days
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Change in plasma P1NP |
30 days
|
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Occurence of thirst
Tidsramme: 30 days
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Occurence of thirst |
30 days
|
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Occurence of headache
Tidsramme: 30 days
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Occurence of headache |
30 days
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Occurence of vertigo
Tidsramme: 30 days
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Occurence of vertigo |
30 days
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Occurence of nausea
Tidsramme: 30 days
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Occurence of nausea |
30 days
|
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Change in general well-being
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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
Tidsramme: 30 days
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Change in grip strength measured with a hand dynamometer |
30 days
|
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Occurence of falls
Tidsramme: 30 days
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Occurence of falls |
30 days
|
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Occurence of fractures
Tidsramme: 30 days
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Occurence of fractures |
30 days
|
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Length of hospital stay
Tidsramme: 30 days
|
Length of hospital stay |
30 days
|
Samarbejdspartnere og efterforskere
Efterforskere
- Ledende efterforsker: Julie Refardt, MD, University Hospital, Basel, Switzerland
Datoer for undersøgelser
Studer store datoer
Studiestart (Faktiske)
Primær færdiggørelse (Faktiske)
Studieafslutning (Faktiske)
Datoer for studieregistrering
Først indsendt
Først indsendt, der opfyldte QC-kriterier
Først opslået (Faktiske)
Opdateringer af undersøgelsesjournaler
Sidste opdatering sendt (Faktiske)
Sidste opdatering indsendt, der opfyldte kvalitetskontrolkriterier
Sidst verificeret
Mere information
Begreber relateret til denne undersøgelse
Yderligere relevante MeSH-vilkår
- Urogenitale sygdomme
- Sygdomme i det endokrine system
- Hjernesygdomme
- Sygdomme i centralnervesystemet
- Sygdomme i nervesystemet
- Mandlige urogenitale sygdomme
- Nyresygdomme
- Urologiske sygdomme
- Urogenitale sygdomme hos kvinder
- Kvinders urogenitale sygdomme og graviditetskomplikationer
- Metaboliske sygdomme
- Sygdomme i fordøjelsessystemet
- Leversygdomme
- Vand-elektrolyt ubalance
- Hypothalamus sygdomme
- Hypofysesygdomme
- Leverinsufficiens
- Ernæringsmæssige og metaboliske sygdomme
- Nyreinsufficiens
- Leversvigt
- Hyponatriæmi
- Uhensigtsmæssig ADH-syndrom
- Empagliflozin
Andre undersøgelses-id-numre
- EMPOWER study
Plan for individuelle deltagerdata (IPD)
Planlægger du at dele individuelle deltagerdata (IPD)?
Lægemiddel- og udstyrsoplysninger, undersøgelsesdokumenter
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