In June 2025, the Swiss National Science Foundation announced their support for the EMPASTONE study as a Investigator-initiated clinical trial (IICT)
EMPASTONE is a randomized, placebo-controlled, multicenter trial with a 2×2 factorial design and a 1:1:1:1 allocation ratio. It assesses efficacies of Empagliflozin and personalized dietary counseling for kidney stone prevention with recurrent calcium kidney stones. The study employs observer, clinician, and participant blinding for the pharmacological intervention arms.
Study Background
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, the SGLT2i empagliflozin reduced the urinary relative supersaturation ratio for calcium phosphate by 36 % compared to placebo in non-diabetic patients 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.
Objective
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.
Study Methodology
400 patients will be recruited from 15 hospitals in Switzerland and 6 hospital in the EU (France, Italy and Germany)
Eligible participants are randomly assigned to receive either empagliflozin 10 mg or matching placebo (encapsulated to ensure identical appearance), administered once daily for a total duration of three years. In parallel, participants undergo randomization to either personalized or generic dietary counselling. Study visits are conducted at baseline and at three-month intervals thereafter up to 36 months, followed by a 30-day post-treatment safety follow-up visit.
Prior to baseline and the visits at months 3, 12, 24, and 36, participants are instructed to perform 24-hour urine collections and to complete 24-hour dietary and fluid intake recordings. These data are used to guide the personalized dietary counselling interventions. NCCT imaging of the kidneys is performed at enrollment and at the 36-month visit to evaluate kidney stone recurrence.
The study further includes optional biobanking of biological samples from participants who provide corresponding written informed consent. Additionally, an optional hemodynamic monitoring substudy is conducted exclusively at the Inselspital, University Hospital Bern, to investigate cardiovascular and renal hemodynamic parameters.
Eligibility Criteria
Inclusion Criteria
- 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 analysed containing 50 % or more of CaOx, CaP, or a mixture of both; inclusion requires availability of such an analysis.
- 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.
Exclusion Criteria
- Known history of secondary or Mendelian cause 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.
- 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 (prisoner), 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.
For more detailed information please visit clinicaltrials.gov or HumRes