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

Study Overview
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Brief Summary
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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.

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

Conditions
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SIADH

Intervention / Treatment
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* Drug: Empagliflozin
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 84 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Empagliflozin<br>Treatment with empagliflozin 25mg once daily for four days | Drug: Empagliflozin<br> <br> |
| Placebo Comparator: Placebo<br>Treatment with Placebo once daily for four days | Other: Placebo<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Serum sodium | 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 | 4 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Serum sodium | Serum sodium concentration 1 day after start of Treatment with study drug | 1 day | 
| Serum sodium | Serum sodium concentration 2 days after start of treatment with study drug | 2 days | 
| Serum sodium | Serum sodium concentration at discharge from hospital | between day 1 to day 30 | 
| Serum sodium | Serum sodium concentration 30 days after start of treatment with study drug | 30 days | 
| Fluid intake | amount of daily fluid intake | 4 days | 
| Urinary excretion | amount of daily urinary excretion | 4 days | 
| Serum electrolytes | change of serum electrolytes from baseline to day 5 | 4 days | 
| Urinary electrolytes | Change of Serum electrolytes from baseline to day 5 | 4 days | 
| Serum osmolality | Change of Serum osmolality from baseline to day 5 | 4 days | 
| Urine osmolality | Change of urinary osmolality from baseline to day 5 | 4 days | 
| Serum glucose | Change of Serum glucose from baseline to day 5 | 4 days | 
| Urinary glucose | Change of urinary Glucose from baseline to day 5 | 4 days | 
| Copeptin | Change of Copeptin from baseline to day 5 | 4 days | 
| Aldosterone | Change of Aldosterone from baseline to day 5 | 4 days | 
| Renin | Change of Renin from baseline to day 5 | 4 days | 
| atrial natriuretic peptide (ANP) | Change of ANP from baseline to day 5 | 4 days | 
| Brain-Natriuretic-Peptide (BNP) | Change of BNP from baseline to day 5 | 4 days | 
| General well-being | course of General well-being from baseline to day 5 as assessed by patient's self-rating score | 4 days | 
| General well-being | course of General well-being from baseline to day 30 as assessed by patient's self-rating score | 30 days | 
| Symptoms of hyponatremia | course of hyponatremia symptoms from baseline to day 5 | 4 days | 
| Symptoms of hyponatremia | Course of hyponatremia symptoms from baseline to day 30 | 30 days | 
| Body weight | Change of Body weight from baseline to day 5 | 4 days | 
| Blood pressure | Change of blood pressure from baseline to day 5 | 4 days | 
| Heart rate | Change of heart rate from baseline to day 5 | 4 days | 
| length of hospital stay | length of hospital stay | 30 days | 
| Treatment escalation | rate of Need for Treatment escalation | 30 days | 
| ICU Admission rate | rate of Admission to ICU | 30 days | 
| Recurrence hyponatremia | recurrence rate hyponatremia | 30 days | 
| Hospital readmission rate | rate of readmission | 30 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Hyponatremia, SGLT2 inhibitor