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

• Status: Not yet recruiting
• Trial end date: 2026-01-01
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 3
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: University Medical Center Groningen
• Collaborator: AstraZeneca
• Treatments: Dapagliflozin

Criteria

Inclusion Criteria:

• Patients with advanced CKD i.e. an eGFR <25 mL/min/1.73m2

• Dialysis patients with a residual diuresis >500 mL/24h (at least 3 months after start of dialysis)

• Transplant patients with an eGFR ≤45 mL/min/1.73m2 (at least 6 months after transplantation)

In addition, to be eligible all subjects must meet all criteria below

• Age >18 years

• Willing to sign informed consent

Exclusion Criteria:

• Mentally incapacitated subjects (i.e. not able to sign informed consent)

• Diagnosis of type 1 diabetes mellitus

• Concurrent treatment with SGLT2 inhibitor

• History of ≥2 urinary tract / genital infections during the last six months

• Life expectancy <6 months in the opinion of the treating physician.

• Scheduled start of dialysis within 3 months or kidney transplantation within 6 months

• In patients with an eGFR <25≤30 mL/min/1.73m2: kidney disease treated with immunosuppressive agents during the last 6 months

• In kidney transplant patients history of acute rejection during the last 6 months

• Active malignancy aside from treated squamous cell or basal cell carcinoma of the skin.

• History of severe hypersensitivity or known severe hepatic impairment (Child-Pugh class C)

• History of severe noncompliance to medical regimens or unwillingness to comply with the study protocol.

• Pregnancy or breastfeeding

• Presence of other transplanted organ besides a kidney transplant