Rationale and design of the Renal Lifecycle Trial assessing the Effect of Dapagliflozin on Cardiorenal Outcomes in Severe Chronic Kidney Disease.

Abstract

Background: 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.

Methods: The Renal Lifecycle trial (NCT05374291) is a pragmatic, international, multicenter, investigator-initiated, randomized, placebo-controlled, clinical trial planned to enroll approximately 1500 patients with 1) an estimated glomerular filtration rate (eGFR) ≤25 ml/min/1.73m2, 2) on hemo- or peritoneal dialysis 3) a kidney transplant and an eGFR ≤45 ml/min/1.73m2, who will be randomized 1:1 to receive either dapagliflozin 10 mg once daily or matching placebo.

Results: The primary endpoint is a composite of heart failure hospitalization, all-cause mortality or, for those not on dialysis, kidney failure (start of dialysis longer than 1 month, receiving a kidney transplantation 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 alpha 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.

Conclusion: The Renal Lifecycle trial aims to investigate the effects of the SGLT2 inhibitor dapagliflozin compared to placebo on the incidence of kidney failure, heart failure, mortality, and safety in three subgroups of patients with advanced CKD.