NCT05374291|Enrolling By InvitationPhase 3DMC

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

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

University Medical Center Groningen ClinicalTrials.gov

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3 other identifiers

2021006172021-005446-152023-508389-13-00

Study Type

interventional

Target

1,750

Locations

6 countries

Sites

Timeline

RegisteredMay 2022

StartedNov 2022

CompletionJul 2027

Brief 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.

Trial Health

On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment

1,750

participants targeted

Target at P75+ for phase_3

Timeline

14mo left

Started Nov 2022

Longer than P75 for phase_3

Geographic Reach

6 countries

90 active sites

Status

enrolling by invitation

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

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Study Timeline

Key milestones and dates

4.6 years study duration

Study Progress75%

Nov 2022Jul 2027

First Submitted

Initial submission to the registry

April 22, 2022

Completed

24 days until next milestone

First Posted

Study publicly available on registry

May 16, 2022

Completed

6 months until next milestone

Study Start

First participant enrolled

November 8, 2022

Completed

4.6 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

July 1, 2027

Expected

Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

July 1, 2027

Last Updated

December 4, 2025

Status Verified

November 1, 2025

Enrollment Period

4.6 years

First QC Date

April 22, 2022

Last Update Submit

November 26, 2025

Conditions

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

Keywords

advanced CKDdialysiskidney transplantall-cause mortalitykidney failurehospitalization for heart failureDapagliflozin

Outcome Measures

Primary Outcomes (1)

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

Secondary Outcomes (4)

Number of participants to reach all-cause mortality
Total study duration intended to last 48 months
Incidence of hospitalization for heart failure
Total study duration intended to last 48 months
Incidence of kidney failure (chronic dialysis, kidney transplantation or mortality due to kidney failure)
Total study duration intended to last 48 months
incidence of the composite outcome (kidney failure, hospitalization for heart failure, and all-cause mortality) in subgroups
Total study duration intended to last 48 months

Other Outcomes (7)

measuring Quality of life with the EQ-5D questionnaire
Total study duration intended to last 48 months
measuring Quality of life with the SF12 questionnaire
Total study duration intended to last 48 months
Cost-effectiveness of SGLT2-inhibition using the Quality of Life-data derived from the EQ-5D and SF-12 questionnaires
Total study duration intended to last 48 months
+4 more other outcomes

Study Arms (2)

Dapagliflozin

EXPERIMENTAL

Dapagliflozin 10 mg/day (oral)

Drug: Dapagliflozin 10 mg/day (oral)

Placebo

PLACEBO COMPARATOR

Placebo 10 mg/day (oral)

Drug: Placebo

Interventions

Dapagliflozin 10 mg/day (oral)DRUG

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

Also known as: Forxiga

Dapagliflozin

PlaceboDRUG

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

Placebo

Eligibility Criteria

Age18 Years+

Sexall

Healthy VolunteersNo

Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

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.

You may not qualify if:

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

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (90)

Canberra Health Services

Canberra, Australian Capital Teritory, Australia

Location

John Hunter Hospital

New Lambton Heights, New South Wales, Australia

Location

Concord Repatriation General Hospital