Bakker Wisanne M, Heerspink Hiddo J L, Berger Stefan P, Wanner Christoph, Badve Sunil V, Arnott Clare, Abrahams Alferso C, van den Born Joost C, van Faassen Tim C, Gaillard Carlo A J M, Gelens Mariëlle A C J, Górris Jose L, Hemmelder Marc H, Jakulj Lily, van Kruijsdijk Rob C M, Kuypers Dirk R J, van der Meer Peter, van der Net Jeroen B, Nijmeijer Heleen H, Vervloet Marc G, de Vries Aiko P J, Walsh Michael, Wang Angela Y, Gansevoort Ron T
Department of Nephrology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
Department of Clinical Pharmacy and Pharmacology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
Nephrol Dial Transplant. 2025 Aug 29;40(9):1746-1755. doi: 10.1093/ndt/gfaf046.
Several clinical trials have shown beneficial effects of sodium-glucose co-transporter 2 (SGLT2) inhibitors on kidney disease progression and cardiovascular morbidity and mortality in patients with chronic kidney disease (CKD) with and without type 2 diabetes mellitus. However, some subgroups of patients with CKD have been excluded from participation in these trials, such as patients with severely impaired kidney function, patients on dialysis and kidney transplant recipients.
The Renal Lifecycle trial (NCT05374291) is a pragmatic, international, multicentre, investigator-initiated, randomized, placebo-controlled clinical trial planned to enrol ≈1500 patients with an estimated glomerular filtration rate (eGFR) ≤25 ml/min/1.73 m2, on haemodialysis or peritoneal dialysis or after a kidney transplant and an eGFR ≤45 ml/min/1.73 m2, who will be randomized 1:1 to receive either dapagliflozin 10 mg once daily or matching placebo.
The primary endpoint is a composite of heart failure hospitalization, all-cause mortality or, for those not on dialysis, kidney failure (start of dialysis >1 month, receiving a kidney transplant or death due to kidney failure). The trial is event driven, indicating that it will end after 468 first primary endpoint events have occurred, with a power of 80% and an α of 0.05 to detect a 25% relative risk reduction assuming an annual 12.5% incidence of the primary outcome. The secondary endpoints include a separate analysis of the incidence of each component of the primary endpoint in the overall trial population as well as the incidence of the combined primary endpoint in each of the three subgroups of patients. Other (exploratory) endpoints are efficacy, safety, tolerability, health-related quality of life and cognition.
The Renal Lifecycle trial aims to investigate the effects of the SGLT2 inhibitor dapagliflozin compared with placebo on the incidence of kidney failure, heart failure, mortality and safety in three subgroups of patients with advanced CKD.
多项临床试验表明，钠-葡萄糖协同转运蛋白2（SGLT2）抑制剂对患有和未患有2型糖尿病的慢性肾脏病（CKD）患者的肾脏疾病进展以及心血管发病率和死亡率具有有益影响。然而，一些CKD患者亚组被排除在这些试验之外，例如肾功能严重受损的患者、接受透析的患者和肾移植受者。
肾脏生命周期试验（NCT05374291）是一项务实的、国际性的、多中心的、研究者发起的、随机的、安慰剂对照临床试验，计划招募约1500例估计肾小球滤过率（eGFR）≤25 ml/min/1.73 m²、正在接受血液透析或腹膜透析或肾移植后且eGFR≤45 ml/min/1.73 m²的患者，这些患者将按1:1随机分组，接受每日一次10 mg达格列净或匹配的安慰剂。
主要终点是心力衰竭住院、全因死亡率的综合指标，对于未接受透析的患者，还包括肾衰竭（开始透析>1个月、接受肾移植或因肾衰竭死亡）。该试验由事件驱动，这表明在发生468例首次主要终点事件后将结束，假设主要结局的年发生率为12.5%，检测相对风险降低25%的效能为80%，α为0.05。次要终点包括在整个试验人群中对主要终点各组成部分的发生率进行单独分析，以及在三个患者亚组中每个亚组的合并主要终点的发生率。其他（探索性）终点是疗效、安全性、耐受性、健康相关生活质量和认知。
肾脏生命周期试验旨在研究与安慰剂相比，SGLT2抑制剂达格列净对晚期CKD三个亚组患者的肾衰竭、心力衰竭、死亡率和安全性发生率的影响。
Zotero 插件