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

Sponsor
University Medical Center Groningen
Study ID
NCT05374291
Phase
PHASE3
Status
Enrolling By Invitation

Conditions

  • Death
  • Heart Failure
  • Kidney Disease, Chronic
  • Kidney Failure
  • Renal Transplant Failure

Eligibility Criteria

Sex
ALL
Age
18 Years - N/A
Healthy Volunteers
Not accepted

Interventions

  • Dapagliflozin 10 mg/day (oral) — DRUG
    Patients take 10 mg dapagliflozin or matching placebo once daily in the morning
  • Placebo — DRUG
    Patients take 10 mg dapagliflozin or matching placebo once daily in the morning

Study Details

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.

Key Dates

Start date
Nov 8, 2022
Status verified
May 2026
Primary completion
Jul 31, 2027
Completion
Jul 31, 2027

Study Design

Enrollment
1,750 participants (estimated)
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION

Arms

  • Experimental: Dapagliflozin
    Dapagliflozin 10 mg/day (oral)
  • Placebo Comparator: Placebo
    Placebo 10 mg/day (oral)

Primary Outcome Measure

Number of partipants with all-cause mortality, kidney failure, and hospitalization for heart failure [ Time Frame: Total study duration intended to last 48 months ]

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