Trial to Assess the Efficacy of EMPAgliflozin and Personalized Dietary Counseling for Kidney STONE Prevention
- Conditions
- Kidney StoneNephrolithiasisDietary Exposure
- Interventions
- Drug: PlaceboBehavioral: Personalized dietary counselingBehavioral: Generic dietary counseling
- Registration Number
- NCT06653738
- Lead Sponsor
- Insel Gruppe AG, University Hospital Bern
- Brief 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.
Recruitment & Eligibility
- Status
- NOT_YET_RECRUITING
- Sex
- All
- Target Recruitment
- 380
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- FACTORIAL
- Arm && Interventions
Group Intervention Description Placebo and personalized dietary counseling Placebo Placebo once daily per os and personalized dietary counseling for 3 years Placebo and personalized dietary counseling Personalized dietary counseling Placebo once daily per os and personalized dietary counseling for 3 years Empagliflozin and generic dietary counseling Empagliflozin 25 MG Empagliflozin 25 mg once daily per os and generic dietary counseling for 3 years Empagliflozin and generic dietary counseling Generic dietary counseling Empagliflozin 25 mg once daily per os and generic dietary counseling for 3 years Placebo and generic dietary counseling Placebo Placebo once daily per os and generic dietary counseling for 3 years Placebo and generic dietary counseling Generic dietary counseling Placebo once daily per os and generic dietary counseling for 3 years Empagliflozin and personalized dietary counseling Empagliflozin 25 MG Empagliflozin 25 mg once daily per os and personalized dietary counseling for 3 years Empagliflozin and personalized dietary counseling Personalized dietary counseling Empagliflozin 25 mg once daily per os and personalized dietary counseling for 3 years
- Primary Outcome Measures
Name Time Method Number of patients with radiologic stone recurrence After 3 years 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).
- Secondary Outcome Measures
Name Time Method Time to symptomatic kidney stone recurrence up to 3 years (time-to-event) From enrollment to the end of treatment at 3 years 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.
Number of symptomatic stone recurrences per patient (cumulative) From enrollment to the end of treatment at 3 years 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.
Trial Locations
- Locations (21)
Hôpital Tenon
🇫🇷Paris, France
Charité University Medicine Berlin
🇩🇪Berlin, Germany
Verona University Hospital
🇮🇹Verona, Italy
University Hospital Amiens-Picardie
🇫🇷Amiens, France
Kantonsspital Aarau
🇨🇭Aarau, Switzerland
Kantonsspital Baden
🇨🇭Baden, Switzerland
University Hospital Basel
🇨🇭Basel, Switzerland
Regionalspital Bellinzona e Valli
🇨🇭Bellinzona, Switzerland
Inselspital Bern
🇨🇭Bern, Switzerland
Kantonsspital Chur
🇨🇭Chur, Switzerland
Kantonsspital Fribourg
🇨🇭Fribourg, Switzerland
University Hospital Geneva (HUG)
🇨🇭Geneva, Switzerland
Lausanne University Hospital (CHUV)
🇨🇭Lausanne, Switzerland
Regionalspital Lugano
🇨🇭Lugano, Switzerland
Kantonsspital Luzern
🇨🇭Luzern, Switzerland
Kantonsspital Neuchâtel
🇨🇭Neuchâtel, Switzerland
Kantonsspital Olten
🇨🇭Olten, Switzerland
Kantonsspital Sion
🇨🇭Sion, Switzerland
Kantonsspital Solothurn
🇨🇭Solothurn, Switzerland
Kantonsspital St. Gallen
🇨🇭St. Gallen, Switzerland
Universitätsspital Zürich
🇨🇭Zürich, Switzerland