Effects of the SGLT2 Inhibitor Empagliflozin in Patients With Euvolemic and Hypervolemic Hyponatremia

NCT04447911 | Recruiting Phase 4

• 1 other identifier: EMPOWER study
• Study Type: interventional
• Target: 172
• Locations: 3 countries
• Sites: 6

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.

Conditions

Hyponatremia; SIADH; Liver Failure; Kidney Failure

Outcome Measures

Primary Outcomes (2)

• Change in average daily area under curve (AUC) for serum sodium concentration

  Change in average daily AUC for serum sodium concentration

  4 days

• Long-term serum sodium change (before/after treatment)

  Absolute change in serum sodium concentration from baseline to end of treatment

  30 days

Secondary Outcomes (33)

• Impact intervention on bodyweight

  30 days

• Impact intervention on blood pressure

  30 days

• Course of serum sodium level

  30 days

• Change of plasma osmolality

  30 days

• Change of urinary osmolality

  30 days

Study Arms (2)

Empagliflozin

EXPERIMENTAL

Empagliflozin (Jardiance)® 25mg per os once daily for 30 days

Drug: Empagliflozin 25 MG

Placebo

PLACEBO COMPARATOR

Placebo (Lactose tablet) per os once daily for 30 days

Drug: Placebo

Interventions

Empagliflozin 25 MG DRUG

Empagliflozin 25mg per os once daily for 30 days

Empagliflozin

Placebo DRUG

Placebo per os once daily for 30 days

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may not qualify if:

• known hypersensitivity or allergy to class of drugs or the investigational product,
• 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
• 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

Sponsors & Collaborators

• University Hospital, Basel, Switzerland: lead
• Luzerner Kantonsspital: collaborator
• Centre Hospitalier Universitaire Vaudois: collaborator

Study Sites (6)

University Hospital of Würzburg, med. Poliklinik

Würzburg, 97080, Germany

RECRUITING

Erasmus Universität Medisch Centrum Rotterdam, Department of Internal Medicine

Rotterdam, 3015, Netherlands

RECRUITING

Centre Hospitalier Universitaire Vaudois (CHUV)

Lausanne, Canton of Vaud, 1011, Switzerland

RECRUITING

University Hospital Basel

Basel, 4031, Switzerland

RECRUITING

Spitalzentrum Biel

Biel, 2502, Switzerland

RECRUITING

Kantonsspital Luzern

Lucerne, 6000, Switzerland

RECRUITING

MeSH Terms

Conditions

Hyponatremia; Inappropriate ADH Syndrome; Liver Failure; Renal Insufficiency

Interventions

empagliflozin

Condition Hierarchy (Ancestors)

Water-Electrolyte Imbalance; Metabolic Diseases; Nutritional and Metabolic Diseases; Pituitary Diseases; Hypothalamic Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Endocrine System Diseases; Hepatic Insufficiency; Liver Diseases; Digestive System Diseases; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases

Study Officials

• Julie Refardt, MD

  University Hospital, Basel, Switzerland

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Mirjam Christ-Crain, Prof

CONTACT

+41 61 328 70 80; Mirjam.Christ-Crain@usb.ch

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Multicentric prospective randomized double-blind placebo-controlled study

Study Record Dates

• First Submitted: June 10, 2020
• First Posted: June 25, 2020
• Study Start: February 4, 2021
• Primary Completion (Estimated): January 1, 2027
• Study Completion (Estimated): February 1, 2027
• Last Updated: November 17, 2025

Record last verified: 2025-11

Data Sharing

• IPD Sharing: Will share

Locations

NL (1); CH (4); DE (1)