Kidney StonePhase 3EMPASTONENCT06653738
Trial to Assess the Efficacy of EMPAgliflozin and Personalized Dietary Counseling for Kidney STONE Prevention
A Phase 3 study testing Empagliflozin 10 MG, Personalized dietary counseling and Generic dietary counseling in people with Kidney Stone and Nephrolithiasis, run by Insel Gruppe AG, University Hospital Bern at 21 sites in 4 countries.
Trial summary
The aim of this randomized trial with a 2-by-2 factorial design is to test the efficacy of the SGLT2 inhibitor empagliflozin and personalized dietary counseling based on 24-hr urine collection results and dietary assessments for kidney stone recurrence prevention in patients with calcium kidney stones. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Kidney Stone, Nephrolithiasis, Dietary Exposure
- What is being tested?
- Empagliflozin 10 MG, Personalized dietary counseling and Generic dietary counseling
- Type of treatment
- Lifestyle or therapy programme
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 400 participants
- Where
- 21 sitesin 4 countries
- Study dates
- 2 Jul 2026to Sep 2030
- Phase
- Phase 3
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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Written, informed consent.
- Age 18 years or older.
- Recurrent kidney stone disease with 2 or more stone episodes in the last 10 years prior to randomization.
- Last kidney stone containing 50% or more of CaOx, CaP or a mixture of both.
- If taking guideline-recommended medications for kidney stone prophylaxis (e.g. citrate salts), patients must have been on a stable regimen for at least 60 days before randomization and willing to remain on this stable regimen for the duration of the study.
Who cannot join
- Known history of secondary or Mendelian causes of calcium nephrolithiasis
- Type I diabetes mellitus
- History of ketoacidosis
- Chronic Kidney Disease (CKD) stage 4 or 5 (defined as CKD-EPI eGFR <30 mL/min)
- Kidney transplant recipient
- History of recurrent urinary tract infections, defined as >3 episodes within the year prior to randomization
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- Heart failure. Symptomatic patients with suspected heart failure must be evaluated before study enrollment
- Treatment with an SGLT2i within 4 weeks prior to randomization.
- Active cancer treatment
- Pregnancy and/or breastfeeding. Women of childbearing potential (i.e., premenopausal women who have not undergone surgical sterilization and are sexually active with a male partner) must have a negative urine or blood pregnancy test prior to enrollment
- Known allergy to the study drug
- Inability to understand and follow the study procedures
- Vulnerable individual, e.g. individual incapable of judgement or currently incarcerated or otherwise institutionalized (priosner), or refugee
- Concomitant participation in another interventional clinical trial within 4 weeks prior to randomization and during the current trial
- Prior enrollment in the EMPASTONE trial
Trial locations and contacts
21 sites in 4 countries. Contact the study team or a site near you to ask about taking part.
21 sites in 4 countries
Switzerland15 sites, 15 recruiting
- Recruiting
Kantonsspital Aarau
Aarau, 5001
Stephan Segerer, +41628389574, Stephan.segerer@ksa.ch
- Recruiting
Kantonsspital Baden
Baden, 5404
Harald Seeger, +41564862707, harald.seeger@ksb.ch
- Recruiting
University Hospital Basel
Basel, 4031
Patrizia Amico, +41 61 265 44 07, patrizia.amico@usb.ch
- Recruiting
Inselspital Bern
Bern, 3010
Daniel Fuster, ++416323144, daniel.fuster@unibe.ch
- Recruiting
Kantonsspital Chur
Chur, 7000
Reto Venzin, +41 812566868, reto.venzin@ksgr.ch
- Not yet recruiting
Kantonsspital Fribourg
Fribourg, 1708
Olivier Bonny, +41263062190, olivier.bonny@h-fr.ch
- Recruiting
University Hospital Geneva (HUG)
Geneva, 1211
Lena Berchtold, +41 22 372 97 62, lena.berchtold@hug.ch
- Recruiting
Lausanne University Hospital (CHUV)
Lausanne, 1011
Nora Schwotzer, +41213141131, nora.schwotzer@chuv.ch
- Not yet recruiting
Kantonsspital Luzern
Lucerne, 6016
Urs Odermatt, +41412055150, urs.odermatt@luks.ch
- Not yet recruiting
Regionalspital Lugano
Lugano, 6900
Antonio Bellasi, +41918116166, Antonio.Bellasi@eoc.ch
- Not yet recruiting
Kantonsspital Neuchâtel
Neuchâtel, 2000
Fabien Stucker, +41327133669, fabien.stucker@rhne.ch
- Not yet recruiting
Kantonsspital Olten
Olten, 4600
Stefan Forster, +41326273121, stefan.forster@spital.so.ch
- Recruiting
Kantonsspital St. Gallen
Sankt Gallen, 9007
Alexander Ritter, +41714941244, alexander.ritter@kssg.ch
- Not yet recruiting
Kantonsspital Sion
Sion, 1950
Daniel Teta, +41276034550, daniel.teta@hopitalvs.ch
- Recruiting
Universitätsspital Zürich
Zurich, 8091
Dusan Harmacek, +41442553384, dusan.harmacek@usz.ch
France3 sites, 3 recruiting
- Not yet recruiting
University Hospital Amiens-Picardie
Amiens, 80054
Dominique Eladari, +33322667832, dominique.eladari@inserm.fr
- Not yet recruiting
Hôpital Tenon
Paris, 75020
Emmanuel Letavernier, +33156016774, emmanuel.letavernier@aphp.fr
- Not yet recruiting
Hôpital Européen Georges Pompidou
Paris, 75908
Marie Courbebaisse, +33 1 56 09 56 25, marie.courbebaisse@aphp.fr
Italy2 sites, 2 recruiting
- Not yet recruiting
Università della Campania "Luigi Vanvitelli"
Naples, 80131
Giovanna Capolongo, +39 388 730 43 78, giovanna.capolongo@unicampania.it
- Not yet recruiting
Verona University Hospital
Verona, 37134
Pietro Manuel Ferraro, +390458124652, pietromanuel.ferraro@univr.it
Germany1 site, 1 recruiting
- Not yet recruiting
Charité University Medicine Berlin
Berlin, 10117
Milen Babic, +49 450 514 172, milen.babic@charite.de
About this study
Official title: Randomized Placebo-controlled Trial to Assess Efficacies of EMPAgliflozin and Personalized Dietary Counselling for Kidney STONE Prevention in Patients With Calcium Kidney Stones Acronym: EMPASTONE Trial
The aim of this randomized trial with a 2-by-2 factorial design is to test the efficacy of the SGLT2 inhibitor empagliflozin and personalized dietary counseling based on 24-hr urine collection results and dietary assessments for kidney stone recurrence prevention in patients with calcium kidney stones.
Study interventions:
- Empagliflozin 10 mg once daily per os for 36 months
- Personalized dietary counseling for 36 months.
Control interventions:
- Placebo once daily per os for 36 months
- Generic dietary counseling for 36 months.
Read the detailed description
Background and rationale:
Nephrolithiasis is a highly prevalent kidney disorder causing substantial morbidity, reduced quality of life and enormous healthcare expenditures worldwide, in large part related to their frequent recurrence. Existing pharmacological strategies for recurrence prevention are limited, and non-pharmacological measures, predominantly dietary counseling practices, vary widely. In observational studies and post-hoc analyses of cardiovascular outcome trials, Sodium-Glucose Co-Transporter 2 inhibitor (SGLT2i) use was associated with a 26-49 % reduction in kidney stone events in patients with type 2 diabetes. In our recent randomized phase 2 SWEETSTONE trial (NCT04911660), the SGLT2i empagliflozin reduced the urinary relative supersaturation ratio for calcium phosphate by 36 % compared to placebo in non-diabetic patients with idiopathic calcium kidney stones, by far the most common kidney stone type. The therapeutic value of SGLT2is in prevention of kidney stone recurrence is unknown, and the optimal dietary counseling approach for patients with kidney stones is undefined.
Objectives:
The primary objective of the study is to assess the efficacy of empagliflozin and a personalized dietary counseling strategy in the secondary prevention of calcium kidney stones, assessed as radiologic stone recurrence at 3 years.
The secondary objectives of the study are to assess the effect of the interventions (empagliflozin versus placebo and personalized versus generic dietary counseling) on both the recurrence and cumulative number of symptomatic kidney stones within 3 years.
Methodology:
The investigators will include 400adult (≥ 18 years) patients with recurrent (≥ 2 kidney stone episodes in the last 10 years) calcium kidney stones (containing 50% or more of calcium oxalate, calcium phosphate or a mixture of both). Patients with known secondary causes of kidney stones will be excluded. In this randomized trial with a 2-by-2 factorial design, patients will be allocated to either empagliflozin 10mg or placebo once daily, and to either personalized or generic dietary counselling according to 24-hr urine results. Randomization will be stratified according to the number of kidney stone episodes during the 10 years before enrolment.
The primary endpoint will be radiologic kidney stone recurrence (a composite of stone growth or new stones formed assessed by computed tomography) at 3 years. Secondary endpoints will be symptomatic kidney stone recurrence up to 3 years, and the number of symptomatic recurrences over 3 years. Exploratory endpoints will be changes in blood and urine parameters, vital signs and weight; asymptomatic kidney stone passage; patient-reported pain and quality of life; and kidney stone event-related health care utilization and cost. Safety endpoints assessed will be the frequency of serious adverse events and of pre-defined adverse events of special interest.
- Conditions
- Kidney Stone, Nephrolithiasis, Dietary Exposure
- Being tested
- Empagliflozin 10 MG, Placebo, Personalized dietary counseling, Generic dietary counseling
- Medical subject headings
- Kidney Calculi, Nephrolithiasis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Empagliflozin 10 MGDrug
Once daily per os for 3 years
PlaceboDrug
Once daily per os for 3 years
Personalized dietary counselingBehavioural
Personalized dietary counseling based on repeat 24-hr urine collections and dietary assessments for 3 years
Generic dietary counselingBehavioural
Generic dietary counseling based on current guidelines without 24-hr urine collection results and without specific dietary assessments for 3 years
| Study group | Role | What they receive |
|---|---|---|
| Empagliflozin and personalized dietary counseling | Experimental | Empagliflozin 10 mg once daily per os and personalized dietary counseling for 3 years Receives: Drug: Empagliflozin 10 MG; Behavioral: Personalized dietary counseling |
| Placebo and personalized dietary counseling | Placebo comparator | Placebo once daily per os and personalized dietary counseling for 3 years Receives: Drug: Placebo; Behavioral: Personalized dietary counseling |
| Empagliflozin and generic dietary counseling | Experimental | Empagliflozin 10 mg once daily per os and generic dietary counseling for 3 years Receives: Drug: Empagliflozin 10 MG; Behavioral: Generic dietary counseling |
| Placebo and generic dietary counseling | Placebo comparator | Placebo once daily per os and generic dietary counseling for 3 years Receives: Drug: Placebo; Behavioral: Generic dietary counseling |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of patients with radiologic stone recurrence
Radiological stone recurrence is defined as a new stone formed or enlargement of a preexisting stone (assessed by low-dose CT of the kidney at the end of the study compared to the low-dose CT of the kidney at the baseline visit).
Measured: After 3 years
Secondary outcomes (2)
Time to symptomatic kidney stone recurrence up to 3 years (time-to-event)
Symptomatic recurrence is defined as the visible passage of a stone with or without accompanying typical symptoms (such as flank or loin pain and hematuria) or as the presence of a symptomatic or asymptomatic stone that was determined to require surgical removal.
Measured: From enrollment to the end of treatment at 3 years
Number of symptomatic stone recurrences per patient (cumulative)
Symptomatic recurrence is defined as the visible passage of a stone with or without accompanying typical symptoms (such as flank or loin pain and hematuria) or as the presence of a symptomatic or asymptomatic stone that was determined to require surgical removal.
Measured: From enrollment to the end of treatment at 3 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Oct 2024
- Study start2 Jul 2026
- Primary completionSep 2030 (estimated)
- Study completionSep 2030 (estimated)
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 Kidney StoneStudies of the same condition, open and under way.
- 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 3
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Factorial
- Model description
- Patients will be allocated to either empagliflozin 10mg or placebo once daily, and to either personalized or generic dietary counseling (2x2 factorial design).
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 400 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Insel Gruppe AG, University Hospital Bern
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Daniel Fuster, Principal investigator, Inselspital, Bern University Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06653738
- Sponsor's protocol ID
- EMPASTONE Trial
- Acronym
- EMPASTONE
- Status last verified
- Jul 2026
- First submitted
- 21 Oct 2024
- Last updated
- 23 Oct 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: Once results have been published, trial data will be accessible to external researchers and coded datasets corresponding to each publication will be made available. Investigators wishing to replicate the analyses or to do an individual patient meta-analysis may request the data to the Sponsor-Investigator.
Publications
Schietzel S, Bally L, Cereghetti G, Faller N, Moor MB, Vogt B, Rintelen F, Trelle S, Fuster D. Impact of the SGLT2 inhibitor empagliflozin on urinary supersaturations in kidney stone formers (SWEETSTONE trial): protocol for a randomised, double-blind, placebo-controlled cross-over trial. BMJ Open. 2022 Mar 14;12(3):e059073. doi: 10.1136/bmjopen-2021-059073.
PubMed 35288397