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ENROLLING BY INVITATION

NCT05374291

PHASE3

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

View on ClinicalTrials.gov

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.

Official title: A Randomized Controlled Clinical Trial to Assess the Effect of Dapagliflozin on Renal and Cardiovascular Outcomes in Patients With Severe Chronic Kidney Disease

Key Details

Gender

All

Age Range

18 Years - Any

Study Type

INTERVENTIONAL

Enrollment

1750

Start Date

2022-11-08

Completion Date

2027-07

Last Updated

2025-12-04

Healthy Volunteers

Conditions

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

Interventions

DRUG

Dapagliflozin 10 mg/day (oral)

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

DRUG

Placebo

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

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

Locations (90)

Canberra Health Services

Canberra, Australian Capital Teritory, Australia

John Hunter Hospital

New Lambton Heights, New South Wales, Australia

Concord Repatriation General Hospital