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

Launched by UNIVERSITY MEDICAL CENTER GRONINGEN · May 9, 2022

Keywords

ClinConnect Summary

The RENAL LIFECYCLE trial is checking whether the medicine dapagliflozin can protect kidneys and the heart in people with very advanced kidney disease. It includes adults 18 and older who have severe chronic kidney disease (an estimated kidney function test called eGFR of 25 or lower), people on dialysis for at least 3 months, and kidney transplant recipients with still-reduced kidney function (eGFR 45 or lower, at least 6 months after transplant). Many clinics across Europe, Australia, and other countries are taking part. Participants are randomly assigned to receive either dapagliflozin 10 mg by mouth once daily or a matching placebo, for the study period.

The study is double-blinded, meaning neither participants nor doctors know who receives the real drug or the placebo. The main goal is to see if dapagliflozin reduces the combined chance of dying from any cause, developing kidney failure, or being hospitalized for heart failure over up to about four years. Participants will have regular visits every 3–6 months to track kidney and heart health, symptoms, and quality of life, along with safety checks. The trial is event-driven and will end after a set number of major outcomes occur, which could make the total study length shorter or longer than four years. There are also sub-studies using heart imaging and other tests to learn more about how the drug might help people with severe kidney disease. The study is led by University Medical Center Groningen, with collaborators including AstraZeneca and the Dutch Kidney Foundation.

Gender

ALL

Eligibility criteria

• Inclusion Criteria:
• • Patients with advanced CKD i.e. an eGFR ≤25 mL/min/1.73m2
• • Dialysis patients (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
• • Pre-dialysis patients with eGFR ≤25 mL/min/1.73m2 have to be on a stable dose (no changes in dose or type of drug) of ACEis or ARBs for at least 4 weeks prior to the screening visit to be eligible to proceed to the randomization visit unless there is documented evidence that the patient does not tolerate an ACEi or ARB. These subjects will maintain their stable doses of ACEis or ARBs throughout the trial (when possible and tolerated by the patient). ACEi or ARBs are not required for patients on maintenance dialysis or kidney transplant recipients.
• 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
• • patients treated for a renal indication during the last 6 months with a course of systemic immunosuppressive agents or intensification of treatment with systemic immunosuppressive agents, such as patients with a kidney transplant and acute rejection or patients with GPA (Morbus Wegener) and a recent flare.
• • 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
• • Severe lactose intolerance
• • Autosomal Dominant Polycystic Kidney Disease (ADPKD) treated with tolvaptan