NCT02874807

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.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
88

participants targeted

Target at P50-P75 for phase_2

Timeline
Completed

Started Sep 2016

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

August 17, 2016

Completed
5 days until next milestone

First Posted

Study publicly available on registry

August 22, 2016

Completed
14 days until next milestone

Study Start

First participant enrolled

September 5, 2016

Completed
2.3 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

December 14, 2018

Completed
1 month until next milestone

Study Completion

Last participant's last visit for all outcomes

January 14, 2019

Completed
Last Updated

June 13, 2019

Status Verified

June 1, 2019

Enrollment Period

2.3 years

First QC Date

August 17, 2016

Last Update Submit

June 12, 2019

Conditions

SIADH

Keywords

HyponatremiaSGLT2 inhibitor

Outcome Measures

Primary Outcomes (1)

  • 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 Outcomes (29)

  • Serum sodium

    1 day

  • Serum sodium

    2 days

  • Serum sodium

    between day 1 to day 30

  • Serum sodium

    30 days

  • Fluid intake

    4 days

  • +24 more secondary outcomes

Study Arms (2)

Empagliflozin

ACTIVE COMPARATOR

Treatment with empagliflozin 25mg once daily for four days

Drug: Empagliflozin

Placebo

PLACEBO COMPARATOR

Treatment with Placebo once daily for four days

Other: Placebo

Interventions

EmpagliflozinDRUG
Empagliflozin
PlaceboOTHER
Placebo

Eligibility Criteria

Age18 Years - 84 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • \- Hyponatremia \<130mmol/l due to SIADH

You may not qualify if:

  • 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
  • +1 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

University Hospital Basel

Basel, 4031, Switzerland

Location

Related Publications (1)

  • 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.

    PMID: 34412521DERIVED

MeSH Terms

Conditions

Inappropriate ADH SyndromeHyponatremia

Interventions

empagliflozin

Condition Hierarchy (Ancestors)

Pituitary DiseasesHypothalamic DiseasesBrain DiseasesCentral Nervous System DiseasesNervous System DiseasesWater-Electrolyte ImbalanceMetabolic DiseasesNutritional and Metabolic DiseasesEndocrine System Diseases

Study Officials

  • Mirjam Christ-Crain, Prof., MD

    University Hospital, Basel, Switzerland

    STUDY DIRECTOR

Study Design

Study Type
interventional
Phase
phase 2
Allocation
RANDOMIZED
Masking
QUADRUPLE
Who Masked
PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

August 17, 2016

First Posted

August 22, 2016

Study Start

September 5, 2016

Primary Completion

December 14, 2018

Study Completion

January 14, 2019

Last Updated

June 13, 2019

Record last verified: 2019-06

Data Sharing

IPD Sharing
Will not share

Locations

CH(1)