HyponatremiaPhase 4EMPOWERNCT04447911
Effects of the SGLT2 Inhibitor Empagliflozin in Patients With Euvolemic and Hypervolemic Hyponatremia
A Phase 4 study testing Empagliflozin 25 MG in people with Hyponatremia and SIADH, run by University Hospital, Basel, Switzerland at 6 sites in 3 countries.
Trial 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). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Hyponatremia, SIADH, Liver Failure
- What is being tested?
- Empagliflozin 25 MG
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 113 participants
- Where
- 6 sitesin 3 countries
- Study dates
- 4 Feb 2021to 17 Sep 2026
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- chronic eu- OR hypervolemic non hyperosmolar (<300 mOsm/kg) hyponatremia (heparin plasma sodium <135 mmol/L on day of inclusion)
Who cannot join
- 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
Show all 19Show fewer
- 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
Trial locations and contacts
6 sites in 3 countries.
6 sites in 3 countries
Switzerland4 sites
University Hospital Basel
Basel, 4031
Spitalzentrum Biel
Biel, 2502
Centre Hospitalier Universitaire Vaudois (CHUV)
Lausanne, Canton of Vaud, 1011
Kantonsspital Luzern
Lucerne, Canton of Lucerne, 6000
Germany1 site
University Hospital of Würzburg, med. Poliklinik
Würzburg, 97080
Netherlands1 site
Erasmus Universität Medisch Centrum Rotterdam, Department of Internal Medicine
Rotterdam, 3015
About this study
Official title: Effects of the SGLT2 Inhibitor Empagliflozin in Patients With Euvolemic and Hypervolemic Hyponatremia - a Multicentric Randomized Double-blind Placebo-controlled Trial (the EMPOWER Study)
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.
- Conditions
- Hyponatremia, SIADH, Liver Failure, Kidney Failure
- Being tested
- Empagliflozin 25 MG, Placebo
- Medical subject headings
- Hyponatremia, Inappropriate ADH Syndrome, Liver Failure, Renal Insufficiency
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Empagliflozin 25 MGDrug
Empagliflozin 25mg per os once daily for 30 days
PlaceboDrug
Placebo per os once daily for 30 days
| Study group | Role | What they receive |
|---|---|---|
| Empagliflozin | Experimental | Empagliflozin (Jardiance)® 25mg per os once daily for 30 days Receives: Drug: Empagliflozin 25 MG |
| Placebo | Placebo comparator | Placebo (Lactose tablet) per os once daily for 30 days Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in average daily area under curve (AUC) for serum sodium concentration
Change in average daily AUC for serum sodium concentration
Measured: 4 days
Long-term serum sodium change (before/after treatment)
Absolute change in serum sodium concentration from baseline to end of treatment
Measured: 30 days
Secondary outcomes (33)
Impact intervention on bodyweight
change of bodyweight
Measured: 30 days
Impact intervention on blood pressure
change of blood pressure
Measured: 30 days
Course of serum sodium level
Course of serum sodium level
Measured: 30 days
Change of plasma osmolality
Change of plasma osmolality
Measured: 30 days
Change of urinary osmolality
Change of urinary osmolality
Measured: 30 days
Change of plasma urea
Change of plasma urea
Measured: 30 days
Change of urinary urea
Change of urinary urea
Measured: 30 days
Change of plasma uric acid
Change of plasma uric acid
Measured: 30 days
Change of urinary uric acid
Change of urinary uric acid
Measured: 30 days
Change of plasma creatinin
Change of plasma creatinin
Measured: 30 days
Change of urinary creatinin
Change of urinary creatinin
Measured: 30 days
Change of plasma potassium
Change of plasma potassium
Measured: 30 days
Change of urinary potassium
Change of urinary potassium
Measured: 30 days
Change in plasma copeptin
Change in plasma copeptin
Measured: 30 days
Change in plasma aldosterone
Change in plasma aldosterone
Measured: 30 days
Change in plasma renin
Change in plasma renin
Measured: 30 days
Change in plasma MR-proANP
Change in plasma MR-proANP
Measured: 30 days
Change in plasma NT-proBNP
Change in plasma NT-proBNP
Measured: 30 days
Change in plasma CTX
Change in plasma CTX
Measured: 30 days
Change in plasma P1NP
Change in plasma P1NP
Measured: 30 days
Occurence of thirst
Occurence of thirst
Measured: 30 days
Occurence of headache
Occurence of headache
Measured: 30 days
Occurence of vertigo
Occurence of vertigo
Measured: 30 days
Occurence of nausea
Occurence of nausea
Measured: 30 days
Change in general well-being
Change in general well-being according to visual analogue scale
Measured: 30 days
Change in quality of life
change in quality of life according to EQ-5D-5L questionnaire
Measured: 30 days
Change in cognitive impairment
Change in cognitive impairment measured with the MoCa test
Measured: 30 days
Change in visual attention
Change in visual attention measured with the trail making test
Measured: 30 days
Change in neuromuscular impairment
Change in neuromuscular impairment measured with the timed up and go test
Measured: 30 days
Change in grip strength
Change in grip strength measured with a hand dynamometer
Measured: 30 days
Occurence of falls
Occurence of falls
Measured: 30 days
Occurence of fractures
Occurence of fractures
Measured: 30 days
Length of hospital stay
Length of hospital stay
Measured: 30 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Jun 2020
- Study start4 Feb 2021
- Primary completion17 Sep 2026
- Study completion17 Sep 2026
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for HyponatremiaStudies of the same condition, open and under way.
- More trials run by University Hospital, Basel, SwitzerlandThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Multicentric prospective randomized double-blind placebo-controlled study
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 113 participants (actual)
Sponsor and investigators
- Lead sponsor
- University Hospital, Basel, Switzerland
- Sponsor type
- University, hospital or other
- Collaborators
- Luzerner Kantonsspital, Centre Hospitalier Universitaire Vaudois
- Responsible party
- Sponsor
- Investigators
- Julie Refardt, MD, Principal investigator, University Hospital, Basel, Switzerland
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04447911
- Sponsor's protocol ID
- EMPOWER study
- Acronym
- EMPOWER
- Status last verified
- Sep 2026
- First submitted
- 10 Jun 2020
- Last updated
- 22 Sep 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 22 Sep 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effects of the SGLT2 Inhibitor Empagliflozin in Patients With Euvolemic and Hypervolemic Hyponatremia - a Multicentric Randomized Double-blind Placebo-controlled Trial (the EMPOWER Study)
- ClinicalTrials.gov ID
- NCT04447911
- Acronym / sponsor ID
- EMPOWER / EMPOWER study
- Conditions
- Hyponatremia, SIADH, Liver Failure, Kidney Failure
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 113 participants (actual)
- Lead sponsor
- University Hospital, Basel, SwitzerlandUniversity, hospital or other
- Collaborators
- Luzerner Kantonsspital, Centre Hospitalier Universitaire Vaudois
- Study start
- 4 Feb 2021 (actual)
- Primary completion
- 17 Sep 2026 (actual)
- Study completion
- 17 Sep 2026 (actual)
- First posted
- 25 Jun 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
- Model description
- Multicentric prospective randomized double-blind placebo-controlled study
| Arm | Type | Receives |
|---|---|---|
| Empagliflozin | Experimental | Drug: Empagliflozin 25 MGEmpagliflozin (Jardiance)® 25mg per os once daily for 30 days |
| Placebo | Placebo comparator | Drug: PlaceboPlacebo (Lactose tablet) per os once daily for 30 days |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (1 listed)
- chronic eu- OR hypervolemic non hyperosmolar (<300 mOsm/kg) hyponatremia (heparin plasma sodium <135 mmol/L on day of inclusion)
Key exclusion criteria (19 listed)
- 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, …)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Empagliflozin 25 MGEmpagliflozin 25mg per os once daily for 30 days | Drug | Empagliflozin |
| PlaceboPlacebo per os once daily for 30 days | Drug | Placebo |
Primary outcome
Change in average daily area under curve (AUC) for serum sodium concentration
Time frame: 4 days
Change in average daily AUC for serum sodium concentration
Long-term serum sodium change (before/after treatment)
Time frame: 30 days
Absolute change in serum sodium concentration from baseline to end of treatment
33 secondary outcomes
Impact intervention on bodyweight
Time frame: 30 days
Impact intervention on blood pressure
Time frame: 30 days
Course of serum sodium level
Time frame: 30 days
Change of plasma osmolality
Time frame: 30 days
Change of urinary osmolality
Time frame: 30 days
Change of plasma urea
Time frame: 30 days
Change of urinary urea
Time frame: 30 days
Change of plasma uric acid
Time frame: 30 days
Change of urinary uric acid
Time frame: 30 days
Change of plasma creatinin
Time frame: 30 days
Change of urinary creatinin
Time frame: 30 days
Change of plasma potassium
Time frame: 30 days
Change of urinary potassium
Time frame: 30 days
Change in plasma copeptin
Time frame: 30 days
Change in plasma aldosterone
Time frame: 30 days
Change in plasma renin
Time frame: 30 days
Change in plasma MR-proANP
Time frame: 30 days
Change in plasma NT-proBNP
Time frame: 30 days
Change in plasma CTX
Time frame: 30 days
Change in plasma P1NP
Time frame: 30 days
Occurence of thirst
Time frame: 30 days
Occurence of headache
Time frame: 30 days
Occurence of vertigo
Time frame: 30 days
Occurence of nausea
Time frame: 30 days
Change in general well-being
Time frame: 30 days
Change in quality of life
Time frame: 30 days
Change in cognitive impairment
Time frame: 30 days
Change in visual attention
Time frame: 30 days
Change in neuromuscular impairment
Time frame: 30 days
Change in grip strength
Time frame: 30 days
Occurence of falls
Time frame: 30 days
Occurence of fractures
Time frame: 30 days
Length of hospital stay
Time frame: 30 days
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Sep 2026.
- Individual participant dataSharing planned: Yes
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Julie Refardt, MD principal investigator
University Hospital, Basel, Switzerland
6 sites in 3 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Empagliflozin 25 MG in people with Hyponatremia and SIADH, run by University Hospital, Basel, Switzerland at 6 sites in 3 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 19 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 22 Sep 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 6 sites in Switzerland, Germany, Netherlands. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in average daily area under curve (AUC) for serum sodium concentration (time frame: 4 days). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Sep 2026.