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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
172
Empagliflozin 25mg per os once daily for 30 days
Placebo per os once daily for 30 days
University Hospital of Würzburg, med. Poliklinik
Würzburg, Germany
RECRUITINGErasmus Universität Medisch Centrum Rotterdam, Department of Internal Medicine
Rotterdam, Netherlands
RECRUITINGCentre Hospitalier Universitaire Vaudois (CHUV)
Lausanne, Canton of Vaud, Switzerland
RECRUITINGUniversity Hospital Basel
Basel, Switzerland
RECRUITINGSpitalzentrum Biel
Biel, Switzerland
RECRUITINGKantonsspital Luzern
Lucerne, Switzerland
RECRUITINGChange in average daily area under curve (AUC) for serum sodium concentration
Change in average daily AUC for serum sodium concentration
Time frame: 4 days
Long-term serum sodium change (before/after treatment)
Absolute change in serum sodium concentration from baseline to end of treatment
Time frame: 30 days
Impact intervention on bodyweight
change of bodyweight
Time frame: 30 days
Impact intervention on blood pressure
change of blood pressure
Time frame: 30 days
Course of serum sodium level
Course of serum sodium level
Time frame: 30 days
Change of plasma osmolality
Change of plasma osmolality
Time frame: 30 days
Change of urinary osmolality
Change of urinary osmolality
Time frame: 30 days
Change of plasma urea
Change of plasma urea
Time frame: 30 days
Change of urinary urea
Change of urinary urea
Time frame: 30 days
Change of plasma uric acid
Change of plasma uric acid
Time frame: 30 days
Change of urinary uric acid
Change of urinary uric acid
Time frame: 30 days
Change of plasma creatinin
Change of plasma creatinin
Time frame: 30 days
Change of urinary creatinin
Change of urinary creatinin
Time frame: 30 days
Change of plasma potassium
Change of plasma potassium
Time frame: 30 days
Change of urinary potassium
Change of urinary potassium
Time frame: 30 days
Change in plasma copeptin
Change in plasma copeptin
Time frame: 30 days
Change in plasma aldosterone
Change in plasma aldosterone
Time frame: 30 days
Change in plasma renin
Change in plasma renin
Time frame: 30 days
Change in plasma MR-proANP
Change in plasma MR-proANP
Time frame: 30 days
Change in plasma NT-proBNP
Change in plasma NT-proBNP
Time frame: 30 days
Change in plasma CTX
Change in plasma CTX
Time frame: 30 days
Change in plasma P1NP
Change in plasma P1NP
Time frame: 30 days
Occurence of thirst
Occurence of thirst
Time frame: 30 days
Occurence of headache
Occurence of headache
Time frame: 30 days
Occurence of vertigo
Occurence of vertigo
Time frame: 30 days
Occurence of nausea
Occurence of nausea
Time frame: 30 days
Change in general well-being
Change in general well-being according to visual analogue scale
Time frame: 30 days
Change in quality of life
change in quality of life according to EQ-5D-5L questionnaire
Time frame: 30 days
Change in cognitive impairment
Change in cognitive impairment measured with the MoCa test
Time frame: 30 days
Change in visual attention
Change in visual attention measured with the trail making test
Time frame: 30 days
Change in neuromuscular impairment
Change in neuromuscular impairment measured with the timed up and go test
Time frame: 30 days
Change in grip strength
Change in grip strength measured with a hand dynamometer
Time frame: 30 days
Occurence of falls
Occurence of falls
Time frame: 30 days
Occurence of fractures
Occurence of fractures
Time frame: 30 days
Length of hospital stay
Length of hospital stay
Time frame: 30 days
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