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

SIADH Clinical Trial

— SAND  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02874807
• Other study ID #: SAND study
• Status: Completed
• Phase: Phase 2/Phase 3
• Start date: September 5, 2016
• Est. completion date: January 14, 2019

Study information

• Verified date: June 2019
• Source: University Hospital, Basel, Switzerland
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 88
• Est. completion date: January 14, 2019
• Est. primary completion date: December 14, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 84 Years

Eligibility

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

Related Conditions & MeSH terms

• Inappropriate ADH Syndrome
• SIADH

Intervention

Drug:
• Empagliflozin

Other:
• Placebo

Locations

Country	Name	City	State
Switzerland	University Hospital Basel	Basel

Sponsors (1)

Lead Sponsor	Collaborator
University Hospital, Basel, Switzerland

Country where clinical trial is conducted

Switzerland, 

Outcome

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