Randomized placebo-controlled trial to assess the efficacy of EMPAgliflozin and professional dietary counselling for kidney STONE recurrence prevention in patients with calcium kidney stones (EMPASTONE)
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 (SGLT2) inhibitor use was associated with a reduction in kidney stone events in patients with type 2 diabetes. In our recent randomized phase 2 trial SWEETSTONE (NCT04911660), the SGLT2 inhibitor empagliflozin significantly improved the urinary lithogenic risk profile compared to placebo in patients with calcium kidney stones, by far the most common kidney stone type.Rationale:The efficacy of SGLT2 inhibitors in the prevention of kidney stone recurrence in patients with kidney stones is unknown. Furthermore, the value of a feasible dietary counselling strategy is unclear.Objective:We plan to conduct a 3-year multicentric, double-blind, placebo-controlled factorial trial to assess the efficacy of empagliflozin with either a standard or intensive dietary counselling strategy in the recurrence prevention of calcium kidney stones in patients.Methodology:We plan to include 338 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 secondary causes of kidney stones, as well as those receiving drugs that interfere with the formation 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 or placebo once daily, and to either standard or intensive dietary counselling. 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 stone formed assessed by computed tomography) at 3 years. Secondary outcomes will be symptomatic kidney stone recurrence up to 3 years, and the number of symptomatic recurrences over 3 years. Exploratory endpoints will be treatment-induced changes in blood and urine parameters; impact of baseline disease severity, biochemical abnormalities and stone composition on treatment response; 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.
Amount: CHF 4,800
Funding type: research
Funder scheme: IICT - PPI Preparatory Grant
Start date: 2024-07-01
End date: 2024-10-31
Investigator: Fuster, Daniel
Institution: University of Berne – BE
Subfield: Pulmonary and Respiratory Medicine
Field: Medicine
Domain: Health Sciences
Funded outputs count: 0
Funder award ID: 229838
OpenAlex ID: G5957657205