Clinical trial NCT02874807: Effects of the SGLT2-inhibitor Empagliflozin on Patients With SIADH - the SAND Study
Official title: Effects of the SGLT2-inhibitor Empagliflozin on Patients With SIADH - the SAND Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
PHASE3
Conditions: SIADH
Keywords: Hyponatremia
SGLT2 inhibitor
Lead sponsor: University Hospital, Basel, Switzerland
Sponsor class: OTHER
First posted: 2016-08-22
Enrollment: 88
Sex: ALL
Minimum age (years): 18
Maximum age (years): 84
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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

Primary outcomes:
measure: Serum sodium
timeFrame: 4 days
Secondary outcomes:
measure: Serum sodium
timeFrame: 1 day
measure: Serum sodium
timeFrame: 2 days
measure: Serum sodium
timeFrame: between day 1 to day 30
measure: Serum sodium
timeFrame: 30 days
measure: Fluid intake
timeFrame: 4 days
measure: Urinary excretion
timeFrame: 4 days
measure: Serum electrolytes
timeFrame: 4 days
measure: Urinary electrolytes
timeFrame: 4 days
measure: Serum osmolality
timeFrame: 4 days
measure: Urine osmolality
timeFrame: 4 days
measure: Serum glucose
timeFrame: 4 days
measure: Urinary glucose
timeFrame: 4 days
measure: Copeptin
timeFrame: 4 days
measure: Aldosterone
timeFrame: 4 days
measure: Renin
timeFrame: 4 days
measure: atrial natriuretic peptide (ANP)
timeFrame: 4 days
measure: Brain-Natriuretic-Peptide (BNP)
timeFrame: 4 days
measure: General well-being
timeFrame: 4 days
measure: General well-being
timeFrame: 30 days
measure: Symptoms of hyponatremia
timeFrame: 4 days
measure: Symptoms of hyponatremia
timeFrame: 30 days
measure: Body weight
timeFrame: 4 days
measure: Blood pressure
timeFrame: 4 days
measure: Heart rate
timeFrame: 4 days
measure: length of hospital stay
timeFrame: 30 days
measure: Treatment escalation
timeFrame: 30 days
measure: ICU Admission rate
timeFrame: 30 days
measure: Recurrence hyponatremia
timeFrame: 30 days
measure: Hospital readmission rate
timeFrame: 30 days
Other outcomes:
Locations:
city: Basel
country: Switzerland
facility: University Hospital Basel
Study officials:
affiliation: University Hospital, Basel, Switzerland
name: Mirjam Christ-Crain, Prof., MD
role: STUDY_DIRECTOR
References:
citation: Nobbenhuis R, Refardt J, Vogt D, Sailer CO, Winzeler B, Christ-Crain M. Can treatment response to SGLT2-inhibitors in syndrome of inappropriate antidiuresis be predicted by copeptin, natriuretic peptides and inflammatory markers? Biomarkers. 2021 Nov;26(7):647-655. doi: 10.1080/1354750X.2021.1970808. Epub 2021 Aug 30.