Effects of the SGLT2 Inhibitor Empagliflozin in Patients With Euvolemic and Hypervolemic Hyponatremia
- Conditions
- SIADHHyponatremiaLiver FailureKidney Failure
- Interventions
- Drug: Placebo
- Registration Number
- NCT04447911
- Lead Sponsor
- University Hospital, Basel, Switzerland
- Brief Summary
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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 172
- chronic eu- OR hypervolemic non hyperosmolar (<300 mOsm/kg) hyponatremia (heparin plasma sodium <135 mmol/L on day of inclusion)
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Empagliflozin Empagliflozin 25 MG Empagliflozin (Jardiance)® 25mg per os once daily for 30 days Placebo Placebo Placebo (Lactose tablet) per os once daily for 30 days
- Primary Outcome Measures
Name Time Method Change in average daily area under curve (AUC) for serum sodium concentration 4 days Change in average daily AUC for serum sodium concentration
Long-term serum sodium change (before/after treatment) 30 days Absolute change in serum sodium concentration from baseline to end of treatment
- Secondary Outcome Measures
Name Time Method Occurence of thirst 30 days Occurence of thirst
Course of serum sodium level 30 days Course of serum sodium level
Change of urinary osmolality 30 days Change of urinary osmolality
Change in plasma copeptin 30 days Change in plasma copeptin
Change in quality of life 30 days change in quality of life according to EQ-5D-5L questionnaire
Impact intervention on bodyweight 30 days change of bodyweight
Change of urinary urea 30 days Change of urinary urea
Change in plasma CTX 30 days Change in plasma CTX
Change of plasma osmolality 30 days Change of plasma osmolality
Change of plasma creatinin 30 days Change of plasma creatinin
Change of urinary potassium 30 days Change of urinary potassium
Occurence of vertigo 30 days Occurence of vertigo
Change in general well-being 30 days Change in general well-being according to visual analogue scale
Impact intervention on blood pressure 30 days change of blood pressure
Change of plasma urea 30 days Change of plasma urea
Change in plasma MR-proANP 30 days Change in plasma MR-proANP
Change in plasma NT-proBNP 30 days Change in plasma NT-proBNP
Change of plasma uric acid 30 days Change of plasma uric acid
Change of urinary uric acid 30 days Change of urinary uric acid
Change in plasma aldosterone 30 days Change in plasma aldosterone
Change in plasma renin 30 days Change in plasma renin
Change of urinary creatinin 30 days Change of urinary creatinin
Change of plasma potassium 30 days Change of plasma potassium
Change in plasma P1NP 30 days Change in plasma P1NP
Occurence of headache 30 days Occurence of headache
Occurence of nausea 30 days Occurence of nausea
Change in cognitive impairment 30 days Change in cognitive impairment measured with the MoCa test
Change in visual attention 30 days Change in visual attention measured with the trail making test
Change in grip strength 30 days Change in grip strength measured with a hand dynamometer
Length of hospital stay 30 days Length of hospital stay
Change in neuromuscular impairment 30 days Change in neuromuscular impairment measured with the timed up and go test
Occurence of falls 30 days Occurence of falls
Occurence of fractures 30 days Occurence of fractures
Trial Locations
- Locations (3)
Centre Hospitalier Universitaire Vaudois (CHUV)
🇨🇭Lausanne, Vaud, Switzerland
University Hospital Basel
🇨🇭Basel, Switzerland
Kantonsspital Luzern
🇨🇭Luzern, Switzerland