STOP-PKD: SGLT2-inhibition to Improve Prognosis in Polycystic Kidney Disease
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 入组人数
- 420
- 试验地点
- 50
- 主要终点
- Chronic eGFR slope
研究概览
简要总结
Autosomal dominant polycystic kidney disease is the most common genetic cause of kidney failure. The only approved treatment for ADPKD - tolvaptan - is limited in its use by massive therapy-associated polyuria. This trial tests if the SGLT2-inhibitor dapagliflozin slows down the loss of kidney function in ADPKD.
详细描述
ADPKD is a genetic disease characterized by the growth of fluid-filled renal cysts, leading to progressive loss of kidney function. SGLT2- inhibitors have recently become available for the treatment of chronic kidney disease (CKD). The landmark trials, which proved the positive effect of SGLT2-inhibitors in CKD, excluded patients with ADPKD. Accordingly, current ADPKD-guidelines do not recommend the use of SGLT2-inhibitors in ADPKD.
This investigator-driven, randomized, placebo-controlled, multi-center, double-blind trial will assess the effect of daily dapagliflozin (10mg) intake on the chronic eGFR-slope in 420 patients with ADPKD. As a secondary endpoint the study will assess a composite endpoint triggered by reaching either 40%-eGFR loss, kidney failure or renal death. Safety aspects will additionally be addressed by an interim safety analysis considering total kidney volume, eGFR and copeptin-levels.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 60 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Male and female patients with ADPKD (modified Ravine criteria) ≥ 18 and ≤ 60 years
- •Patients 18 - 39 years: eGFR ≥25 ml/min; patients 40 - 60 years: eGFR ≥25 and <90 ml/min/1.73 m2
- •Indicators of rapid progression, either of the following:
- •Mayo class 1D-E
- •Mayo class 1C AND EITHER
- •Truncating PKD1 mutation OR
- •eGFR loss > 3ml/min/year (determined by ≥ 4 creatinine values within 4 years, ≥ 6 months measurement intervals) OR
- •PROPKD score > 6 (patient history)
- •IF patient is on ACE-I /ARBs: stable dose for 4 weeks before screening
排除标准
- •Treatment with tolvaptan, somatostatin analogue, lithium or SGLT2i within the last 3 months before screening
- •Medical history of diabetic ketoacidosis, necrotizing fasciitis or organ transplantation
- •Diabetes mellitus type 1 or any type of diabetes mellitus due to insulin deficiency
- •Uncontrolled ongoing urinary tract or genital infections
- •Known intolerance of the study medication ingredients
- •Uncontrolled grade 2 hypertension (>160/100 mmHg)
- •Symptomatic hypotension, or systolic blood pressure <90 mmHg
- •Primary renal disease other than ADPKD
- •Hepatic impairment (aspartate transaminase [AST] or alanine transaminase [ALT]>3x the up-per limit of normal [ULN]; or total bilirubin >2x ULN at time of enrolment)
- •Pregnancy, breastfeeding or women of child-bearing potential not using effective contraception method
- •Not able to comply with the study protocol, in the investigator's judgement
- •Not able to provide informed consent
- •Participation in any other interventional clinical trial in the last 2 months
研究组 & 干预措施
Dapagliflozin 10 mg
干预措施: Dapagliflozin 10 mg (Drug)
Placebo
干预措施: Matching Placebo (Drug)
结局指标
主要结局
Chronic eGFR slope
时间窗: week 6 up to week 156 (end of treatment)
The annual chronic eGFR slope will be calculated using all available serum creatinine values from week 6 to week 156 (end of treatment), using linear mixed models.
Chronic eGFR slope
时间窗: week 6 up to week 156 (end of treatment)
The annual chronic eGFR slope will be calculated using all available serum creatinine values from week 6 to week 156 (end of treatment), using linear mixed models.
次要结局
- Time to first occurrence of a composite renal endpoint(From randomization (week 0) until end of follow-up (up to week 168))
- Incidence of serious adverse events (SAEs)(From randomization (week 0) until end of follow-up (week 168))
- Incidence of adverse events of special interest (AESIs)(From randomization (week 0) until end of follow-up (week 168))
- Change in total kidney volume (TKV) after 1 year(Baseline (week -4 until week 0) to week 48 (first 150 patients))
- Change in eGFR from pre-treatment to post-treatment (off-treatment values)(Week -4 to Week 168)
- Incidence of serious adverse events (SAEs)(From randomization (week 0) until end of follow-up (week 168))
- Change in eGFR from pre-treatment to post-treatment (off-treatment values)(Week -4 to Week 168)
- Time to first occurrence of a composite renal endpoint(From randomization (week 0) until end of follow-up (up to week 168))
- Incidence of adverse events of special interest (AESIs)(From randomization (week 0) until end of follow-up (week 168))
- Change in total kidney volume (TKV) after 1 year(Baseline (week -4 until week 0) to week 48 (first 150 patients))
研究者
Roman Müller
Prof. Dr. med.
University Hospital of Cologne