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Effects of the SGLT2-inhibitor Empagliflozin on Patients With SIADH - the SAND Study

Phase 2
Completed
Conditions
SIADH
Interventions
Other: Placebo
Registration Number
NCT02874807
Lead Sponsor
University Hospital, Basel, Switzerland
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.

Detailed Description

Not available

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
88
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

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
PlaceboPlaceboTreatment with Placebo once daily for four days
EmpagliflozinEmpagliflozinTreatment with empagliflozin 25mg once daily for four days
Primary Outcome Measures
NameTimeMethod
Serum sodium4 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 Outcome Measures
NameTimeMethod
Serum glucose4 days

Change of Serum glucose from baseline to day 5

Blood pressure4 days

Change of blood pressure from baseline to day 5

Urinary excretion4 days

amount of daily urinary excretion

Serum electrolytes4 days

change of serum electrolytes from baseline to day 5

Urinary electrolytes4 days

Change of Serum electrolytes from baseline to day 5

Copeptin4 days

Change of Copeptin from baseline to day 5

Body weight4 days

Change of Body weight from baseline to day 5

Treatment escalation30 days

rate of Need for Treatment escalation

Hospital readmission rate30 days

rate of readmission

General well-being30 days

course of General well-being from baseline to day 30 as assessed by patient's self-rating score

Fluid intake4 days

amount of daily fluid intake

Serum osmolality4 days

Change of Serum osmolality from baseline to day 5

Renin4 days

Change of Renin from baseline to day 5

ICU Admission rate30 days

rate of Admission to ICU

Serum sodium30 days

Serum sodium concentration 30 days after start of treatment with study drug

Urine osmolality4 days

Change of urinary osmolality from baseline to day 5

Urinary glucose4 days

Change of urinary Glucose from baseline to day 5

atrial natriuretic peptide (ANP)4 days

Change of ANP from baseline to day 5

Aldosterone4 days

Change of Aldosterone from baseline to day 5

Brain-Natriuretic-Peptide (BNP)4 days

Change of BNP from baseline to day 5

Heart rate4 days

Change of heart rate from baseline to day 5

length of hospital stay30 days

length of hospital stay

Symptoms of hyponatremia30 days

Course of hyponatremia symptoms from baseline to day 30

Recurrence hyponatremia30 days

recurrence rate hyponatremia

Trial Locations

Locations (1)

University Hospital Basel

🇨🇭

Basel, Switzerland

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