SIADHPhase 2/3SANDNCT02874807
Effects of the SGLT2-inhibitor Empagliflozin on Patients With SIADH - the SAND Study
A Phase 2/3 study testing Empagliflozin in people with SIADH, run by University Hospital, Basel, Switzerland at 1 site in Switzerland.
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. Read more about this study
- Who is it for?
- Ages 18 to 84 years
- Conditions the study is for
- SIADH
- What is being tested?
- Empagliflozin
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 88 participants
- Where
- 1 siteSwitzerland
- Study dates
- 5 Sep 2016to 14 Jan 2019
- Phase
- Phase 2/3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 84 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Hyponatremia <130mmol/l due to SIADH
Who cannot join
- 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
Show all 16Show fewer
- 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
Trial locations and contacts
1 site in 1 country.
About this study
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.
Read more
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.
- Conditions
- SIADH
- Being tested
- Empagliflozin, Placebo
- Keywords
- Hyponatremia, SGLT2 inhibitor
- Medical subject headings
- Inappropriate ADH Syndrome, Hyponatremia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
EmpagliflozinDrug
PlaceboOther
| Study group | Role | What they receive |
|---|---|---|
| Empagliflozin | Active comparator | Treatment with empagliflozin 25mg once daily for four days Receives: Drug: Empagliflozin |
| Placebo | Placebo comparator | Treatment with Placebo once daily for four days Receives: Other: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 4 days
Secondary outcomes (29)
Serum sodium
Serum sodium concentration 1 day after start of Treatment with study drug
Measured: 1 day
Serum sodium
Serum sodium concentration 2 days after start of treatment with study drug
Measured: 2 days
Serum sodium
Serum sodium concentration at discharge from hospital
Measured: between day 1 to day 30
Serum sodium
Serum sodium concentration 30 days after start of treatment with study drug
Measured: 30 days
Fluid intake
amount of daily fluid intake
Measured: 4 days
Urinary excretion
amount of daily urinary excretion
Measured: 4 days
Serum electrolytes
change of serum electrolytes from baseline to day 5
Measured: 4 days
Urinary electrolytes
Change of Serum electrolytes from baseline to day 5
Measured: 4 days
Serum osmolality
Change of Serum osmolality from baseline to day 5
Measured: 4 days
Urine osmolality
Change of urinary osmolality from baseline to day 5
Measured: 4 days
Serum glucose
Change of Serum glucose from baseline to day 5
Measured: 4 days
Urinary glucose
Change of urinary Glucose from baseline to day 5
Measured: 4 days
Copeptin
Change of Copeptin from baseline to day 5
Measured: 4 days
Aldosterone
Change of Aldosterone from baseline to day 5
Measured: 4 days
Renin
Change of Renin from baseline to day 5
Measured: 4 days
atrial natriuretic peptide (ANP)
Change of ANP from baseline to day 5
Measured: 4 days
Brain-Natriuretic-Peptide (BNP)
Change of BNP from baseline to day 5
Measured: 4 days
General well-being
course of General well-being from baseline to day 5 as assessed by patient's self-rating score
Measured: 4 days
General well-being
course of General well-being from baseline to day 30 as assessed by patient's self-rating score
Measured: 30 days
Symptoms of hyponatremia
course of hyponatremia symptoms from baseline to day 5
Measured: 4 days
Symptoms of hyponatremia
Course of hyponatremia symptoms from baseline to day 30
Measured: 30 days
Body weight
Change of Body weight from baseline to day 5
Measured: 4 days
Blood pressure
Change of blood pressure from baseline to day 5
Measured: 4 days
Heart rate
Change of heart rate from baseline to day 5
Measured: 4 days
length of hospital stay
length of hospital stay
Measured: 30 days
Treatment escalation
rate of Need for Treatment escalation
Measured: 30 days
ICU Admission rate
rate of Admission to ICU
Measured: 30 days
Recurrence hyponatremia
recurrence rate hyponatremia
Measured: 30 days
Hospital readmission rate
rate of readmission
Measured: 30 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Aug 2016 (estimated)
- Study start5 Sep 2016
- Primary completion14 Dec 2018
- Study completion14 Jan 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for SIADHStudies of the same condition, open and under way.
- More trials run by University Hospital, Basel, SwitzerlandThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2/3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 88 participants (actual)
Sponsor and investigators
- Lead sponsor
- University Hospital, Basel, Switzerland
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Mirjam Christ-Crain, Prof., MD, Study director, University Hospital, Basel, Switzerland
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02874807
- Sponsor's protocol ID
- SAND study
- Acronym
- SAND
- Status last verified
- Jun 2019
- First submitted
- 17 Aug 2016
- Last updated
- 13 Jun 2019
- Results posted
- No
- Data monitoring committee
- Yes
- Individual data sharing
- No
Publications
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.
PubMed 34412521
Study at a glance
From the registry record, last updated by the sponsor on 13 Jun 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effects of the SGLT2-inhibitor Empagliflozin on Patients With SIADH - the SAND Study
- ClinicalTrials.gov ID
- NCT02874807
- Acronym / sponsor ID
- SAND / SAND study
- Conditions
- SIADH
- Keywords
- Hyponatremia, SGLT2 inhibitor
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 88 participants (actual)
- Lead sponsor
- University Hospital, Basel, SwitzerlandUniversity, hospital or other
- Study start
- 5 Sep 2016 (actual)
- Primary completion
- 14 Dec 2018 (actual)
- Study completion
- 14 Jan 2019 (actual)
- First posted
- 22 Aug 2016 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Empagliflozin | Active comparator | Drug: EmpagliflozinTreatment with empagliflozin 25mg once daily for four days |
| Placebo | Placebo comparator | Other: PlaceboTreatment with Placebo once daily for four days |
Who may qualify
- Ages
- 18 to 84 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (1 listed)
- Hyponatremia <130mmol/l due to SIADH
Key exclusion criteria (16 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Empagliflozin | Drug | Empagliflozin |
| Placebo | Other | Placebo |
Primary outcome
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
29 secondary outcomes
Serum sodium
Time frame: 1 day
Serum sodium
Time frame: 2 days
Serum sodium
Time frame: between day 1 to day 30
Serum sodium
Time frame: 30 days
Fluid intake
Time frame: 4 days
Urinary excretion
Time frame: 4 days
Serum electrolytes
Time frame: 4 days
Urinary electrolytes
Time frame: 4 days
Serum osmolality
Time frame: 4 days
Urine osmolality
Time frame: 4 days
Serum glucose
Time frame: 4 days
Urinary glucose
Time frame: 4 days
Copeptin
Time frame: 4 days
Aldosterone
Time frame: 4 days
Renin
Time frame: 4 days
atrial natriuretic peptide (ANP)
Time frame: 4 days
Brain-Natriuretic-Peptide (BNP)
Time frame: 4 days
General well-being
Time frame: 4 days
General well-being
Time frame: 30 days
Symptoms of hyponatremia
Time frame: 4 days
Symptoms of hyponatremia
Time frame: 30 days
Body weight
Time frame: 4 days
Blood pressure
Time frame: 4 days
Heart rate
Time frame: 4 days
length of hospital stay
Time frame: 30 days
Treatment escalation
Time frame: 30 days
ICU Admission rate
Time frame: 30 days
Recurrence hyponatremia
Time frame: 30 days
Hospital readmission rate
Time frame: 30 days
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Jun 2019.
- Derived from this study: PubMed 34412521Nobbenhuis 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.
- Individual participant dataSharing planned: No
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Active, not recruitingObservational study
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Recruiting
Urea for Treatment of Hyponatremia in Patients With SIAD Unresponsive to Fluid Restriction
SIAD - Syndrome of Inappropriate Antidiuresis
Recruiting
Protein Supplementation in Hyponatremia Due to the Syndrome of Inappropriate Antidiuresis
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Active, not recruiting
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Mirjam Christ-Crain, Prof., MD study director
University Hospital, Basel, Switzerland
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2/3 study testing Empagliflozin in people with SIADH, run by University Hospital, Basel, Switzerland at 1 site in Switzerland.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 13 Jun 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Switzerland. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Serum sodium (time frame: 4 days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02874807, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 Jun 2019.