The RENAL LIFECYCLE Trial: A RCT to Assess the Effect of Dapagliflozin on Renal and Cardiovascular Outcomes in Patients With Severe CKD

Condition(s) studied

Investigational drug(s) / intervention(s)

Dapagliflozin 10 mg/day (oral): Patients take 10 mg dapagliflozin or matching placebo once daily in the morning

Placebo: Patients take 10 mg dapagliflozin or matching placebo once daily in the morning

Study summary

Rationale:

Sodium glucose co transporter 2 (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 have also specific reno- and cardioprotective effects. Remarkably, the trials that have been performed thus far excluded patients with an eGFR below 25 mL/min/1.73m2 at inclusion, prevalent dialysis patients, and kidney transplant recipients. This is unfortunate, because especially these patients are at high risk of reaching kidney failure requiring dialysis, cardiovascular complications and mortality, whereas there are only few proven effective therapies. There is emerging evidence from experimental studies and post hoc-analyses of randomized clinical trials that SGLT2 inhibitors may also be effective in preventing cardiovascular and mortality outcomes in these 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\<30 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 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 stabilize kidney function, and these agents were well tolerated and safe. Taken these findings together there is a sound rationale to study the long-term reno- and cardioprotective efficacy and safety of SGLT2 inhibitors in patients with severe CKD.

There are two cardiac sub-studies: the cardiac magnetic resonance imaging (MRI) sub-study and the echocardiography sub-study. The echocardiography sub-study is referred to as the "SGLT-2-inhibitors to Target Heart Failure in Peritoneal Dialysis" (STOP-HF-in-PD) study.

Eligibility

Primary outcome measure(s)

• Number of partipants with all-cause mortality, kidney failure, and hospitalization for heart failure — Total study duration intended to last 48 months
  To determine whether dapagliflozin is superior to placebo in reducing the incidence of the primary composite endpoint Combined endpoint of all-cause mortality, kidney failure, and hospitalization for heart failure in the overall study population

Trial sites (102)

+ 62 more sites — see the full list on the official registry below.

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