NCT06653738

Trial to Assess the Efficacy of EMPAgliflozin and Personalized Dietary Counseling for Kidney STONE Prevention

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

• Status: Not Yet Recruiting
• Phase: Phase 3
• Study type: Interventional
• Enrollment: 380 (estimated)
• Sponsor: Insel Gruppe AG, University Hospital Bern · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

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. Study interventions: * Empagliflozin 25 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.

Detailed description

Background: Nephrolithiasis is a highly prevalent kidney disorder that causes substantial morbidity, reduced quality of life and enormous healthcare expenditures worldwide. Kidney stones recur frequently, with 10-year recurrence rates of up to 80 %. Existing pharmacological strategies for the prevention of kidney stone recurrence are limited, and dietary counselling practices for patients with kidney stones vary widely. In observational studies and post-hoc analyses of cardiovascular outcome trials, sodium-glucose cotransporter 2 inhibitor (SGLT2i) use was associated with a reduction in kidney stone events in patients with type 2 diabetes. In the recent randomized phase 2 trial SWEETSTONE (NCT04911660), the SGLT2i empagliflozin significantly improved the urinary lithogenic risk profile compared to placebo in non-diabetic patients with calcium kidney stones, by far the most common kidney stone type. Rationale: The efficacy of SGLT2is in the prevention of kidney stone recurrence in patients with kidney stones is unknown. Furthermore, the optimal dietary counseling approach for individuals with kidney stones remains unclear. Objective: The investigators plan to conduct a 3-year multicentric, double-blind, placebo-controlled factorial trial to assess the efficacy of empagliflozin with either a personalized or generic dietary counselling strategy for recurrence prevention in patients with calcium kidney stones. Methodology: The investigators will include 380 adult (≥ 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 25 mg 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

Interventions

Type	Name	Description
DRUG	Empagliflozin 25 MG	Once daily per os for 3 years
DRUG	Placebo	Once daily per os for 3 years
BEHAVIORAL	Personalized dietary counseling	Personalized dietary counseling based on repeat 24-hr urine collections and dietary assessments for 3 years
BEHAVIORAL	Generic dietary counseling	Generic dietary counseling based on current guidelines without 24-hr urine collection results and without specific dietary assessments for 3 years

Timeline

• Start date: 2025-05-01
• Primary completion: 2030-02-01
• Completion: 2030-06-01
• First posted: 2024-10-22
• Last updated: 2024-10-22

Locations

21 sites across 4 countries: France, Germany, Italy, Switzerland