Effects of the SGLT2-inhibitor Empagliflozin on Patients With SIADH - the SAND Study
Trial Snapshot
- Phase
- Phase 2
- Status
- Completed
- Sponsor
- Enrollment
- 88
- Locations
- 1
- Primary Endpoint
- Serum sodium
Study Overview
Brief Summary
Syndrome of inappropriate antidiuresis (SIADH) is characterized by an imbalance of antidiuretic vasopressin (AVP) secretion. The impaired AVP regulation leads to water retention and secondary natriuresis and is a common cause for hyponatremia.
The therapeutic options, aside from treating the underlying disease, depend upon the onset and severity of the symptoms and involve usually fluid restriction or hypertonic saline infusion. Alternative therapeutic options are loop diuretics, administration of oral urea or vasopressin receptor antagonists (vaptans). Despite those options, there are a considerable number of patients which do not sufficiently respond, making additional therapy necessary.
Empagliflozin (Jardiance)® is a sodium glucose co-transporter 2 (SGLT2)-inhibitor, which is a new treatment option developed for patients with diabetes mellitus type 2. The SGLT2 is expressed in the proximal tubule and reabsorbs approximately 90 percent of the filtered glucose. The inhibition of SGLT2 results in renal excretion of glucose with subsequent osmotic diuresis. This mechanism could result in a therapeutic effect in patients with hypotonic hyponatremia as in SIADH.
The aim of this study is to evaluate whether empagliflozin (Jardiance)® has an effect on the serum sodium levels of patients with SIADH.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Eligibility Criteria
- Ages
- 18 Years to 84 Years (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Hyponatremia <130mmol/l due to SIADH
Exclusion Criteria
- •any Treatment for SIADH during >48h before study start
- •severe illness with ICU-Admission
- •Treatment with 3% sodium Chloride (NaCl) solution
- •uncontrolled hypothyroidism
- •uncontrolled adrenal insufficiency
- •severe renal impairment (GFR <30ml/min), end stage renal disease
- •severe hepatic impairment (Child-Pugh class C)
- •systolic blood pressure <90mmHg
- •Diabetes mellitus type 1
- •acute myocardial infarction or chronic venous insufficiency (CVI)
- •Treatment with SGLT2 Inhibitor, Lithium Chloride or Urea
- •recurrent urinary-/genital tract infections
- •contraindication for lowering blood pressure
- •severe immunosuppression
- •pregnancy or breastfeeding
- •palliative care
Arms & Interventions
Empagliflozin
Treatment with empagliflozin 25mg once daily for four days
Intervention: Empagliflozin (Drug)
Placebo
Treatment with Placebo once daily for four days
Intervention: Placebo (Other)
Outcomes
Primary Outcomes
Serum sodium
Time Frame: 4 days
The primary outcome is the change in serum sodium concentration from baseline to day 5, i.e. 4 days after start of treatment with study drug
Secondary Outcomes
- Serum glucose(4 days)
- Urinary glucose(4 days)
- atrial natriuretic peptide (ANP)(4 days)
- Urinary excretion(4 days)
- Serum electrolytes(4 days)
- Urinary electrolytes(4 days)
- Copeptin(4 days)
- Body weight(4 days)
- Treatment escalation(30 days)
- General well-being(30 days)
- Fluid intake(4 days)
- Serum osmolality(4 days)
- Renin(4 days)
- ICU Admission rate(30 days)
- Hospital readmission rate(30 days)
- Serum sodium(30 days)
- Urine osmolality(4 days)
- Aldosterone(4 days)
- Brain-Natriuretic-Peptide (BNP)(4 days)
- Blood pressure(4 days)
- Heart rate(4 days)
- length of hospital stay(30 days)
- Symptoms of hyponatremia(30 days)
- Recurrence hyponatremia(30 days)