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

Sponsor
University Hospital, Basel, Switzerland
Study ID
NCT04447911
Phase
PHASE4
Status
Recruiting
Apply to this trial

Conditions

  • Hyponatremia
  • Kidney Failure
  • Liver Failure
  • SIADH

Eligibility Criteria

Sex
ALL
Age
18 Years - N/A
Healthy Volunteers
Not accepted

Interventions

  • Empagliflozin 25 MG — DRUG
    Empagliflozin 25mg per os once daily for 30 days
  • Placebo — DRUG
    Placebo per os once daily for 30 days

Study Details

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.

Key Dates

Start date
Feb 4, 2021
Status verified
Nov 2025
Primary completion
Jan 31, 2027
Completion
Feb 28, 2027

Study Design

Enrollment
172 participants (estimated)
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT

Arms

  • Experimental: Empagliflozin
    Empagliflozin (Jardiance)® 25mg per os once daily for 30 days
  • Placebo Comparator: Placebo
    Placebo (Lactose tablet) per os once daily for 30 days

Primary Outcome Measure

Change in average daily area under curve (AUC) for serum sodium concentration [ Time Frame: 4 days ]

Central Contacts

Related Studies