The RENAL LIFECYCLE Trial: Assessing the effect of dapagliflozin on patients with severe chronic kidney disease
Background
SGLT2 inhibitors are a relatively new class of agents, originally developed as oral antihyperglycemic drugs. SGLT2 inhibitors are clinically available since 2012 for the treatment of patients with diabetes mellitus type 2. Later, SGLT2 inhibitors appeared to also have specific reno- and cardioprotective effects. Notably, the trials that have been performed thus far have excluded patients with an eGFR below 25 mL/min/1.73m2 at inclusion, prevalent dialysis patients, and kidney transplant recipients. These patients are at greater risk of developing kidney failure requiring dialysis, cardiovascular complications and mortality, however currently there are only a few proven effective therapies for these conditions.
There is emerging evidence from experimental studies and post hoc-analyses of randomised clinical trials that SGLT2 inhibitors may also be effective in preventing cardiovascular and mortality outcomes in patients with severe CKD, including patients receiving dialysis or living with a kidney transplant. For instance, subgroup analysis of the DAPA-CKD trial comparing 624 patients with an eGFR <30mL/min/1.73m2 to the remainder of the trial population with better kidney function, demonstrated that the efficacy of the SGLT2 inhibitor dapagliflozin in reducing cardiovascular, heart failure and renal outcomes persisted in the population with severely impaired kidney function. Furthermore, in the DAPA-CKD trial patients continued to use dapagliflozin or placebo when dialysis was initiated. In the subgroup of patients who initiated dialysis, dapagliflozin was associated with a relative risk reduction for mortality of 21%. Finally, in kidney transplant recipients, SGLT2 inhibitors have been shown to be effective in lowering HbA1c, body weight, blood pressure and stabilising kidney function, and these agents were well tolerated and safe. These data confirm there is a sound rationale to study the long-term reno- and cardioprotective efficacy and safety of SGLT2 inhibitors in patients with severe CKD.
Aim
To establish the reno- and cardioprotective efficacy and safety of dapagliflozin in patients with severe CKD.
Research Methodology
The RENAL LIFECYCLE Trial is a multi-centre, randomised, controlled, double blinded, pragmatic, interventional trial. The intervention is dapagliflozin 10 mg/day or matched placebo daily. The global participant recruitment target is 1500 (750 per randomised group). The recruitment phase is 18-month, follow-up phase is 30-months after enrolment of the last participant and the total study duration is intended to last 48 months. The study is endpoint driven so trial duration may therefore be shorter or longer than the intended 48 months. The global trial is being conducted in The Netherlands, Germany, Australia and Belgium.
Current Status
Currently the trial is mostly in recruitment phase in Australia, with a few new sites in start-up phase.
