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
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 入组人数
- 400
- 试验地点
- 21
- 主要终点
- Number of patients with radiologic stone recurrence
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Factorial
- 主要目的
- Prevention
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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.
排除标准
- •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
- •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
研究组 & 干预措施
Placebo and personalized dietary counseling
Placebo once daily per os and personalized dietary counseling for 3 years
干预措施: Placebo (Drug)
Placebo and generic dietary counseling
Placebo once daily per os and generic dietary counseling for 3 years
干预措施: Placebo (Drug)
Empagliflozin and generic dietary counseling
Empagliflozin 10 mg once daily per os and generic dietary counseling for 3 years
干预措施: Empagliflozin 10 MG (Drug)
Empagliflozin and personalized dietary counseling
Empagliflozin 10 mg once daily per os and personalized dietary counseling for 3 years
干预措施: Personalized dietary counseling (Behavioral)
Placebo and personalized dietary counseling
Placebo once daily per os and personalized dietary counseling for 3 years
干预措施: Personalized dietary counseling (Behavioral)
Empagliflozin and generic dietary counseling
Empagliflozin 10 mg once daily per os and generic dietary counseling for 3 years
干预措施: Generic dietary counseling (Behavioral)
Placebo and generic dietary counseling
Placebo once daily per os and generic dietary counseling for 3 years
干预措施: Generic dietary counseling (Behavioral)
Empagliflozin and personalized dietary counseling
Empagliflozin 10 mg once daily per os and personalized dietary counseling for 3 years
干预措施: Empagliflozin 10 MG (Drug)
结局指标
主要结局
Number of patients with radiologic stone recurrence
时间窗: 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).
次要结局
- Time to symptomatic kidney stone recurrence up to 3 years (time-to-event)(From enrollment to the end of treatment at 3 years)
- Number of symptomatic stone recurrences per patient (cumulative)(From enrollment to the end of treatment at 3 years)