A Phase 3 interventional study of Dapagliflozin 10 mg/day (oral) and Placebo in Kidney Disease, Chronic, Renal Transplant Failure and Heart Failure, sponsored by University Medical Center Groningen. Active, not recruiting at 101 sites in 6 countries. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2026-10-08.
Sponsored by University Medical Center Groningen · Phase 3, Interventional, and Prevention
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.
Objective:
To establish the reno- and cardioprotective efficacy and safety of dapagliflozin in patients with severe CKD
Study design:
Multicenter, randomized, controlled, double blinded, pragmatic, interventional trial
Study population:
Intervention:
Dapagliflozin 10 mg/day or matching placebo
Primary outcome measure:
Combined endpoint of all-cause mortality, kidney failure, and hospitalization for heart failure in the overall study population
Study duration:
18 month recruitment phase, 30 month follow-up after enrollment of the last patient: Total study duration intended to last 48 months. It should be noted that the trial is event driven and will be terminated when 468 primary composite outcomes have occurred. The exact trial duration may therefore be shorter or longer than the intended 48 months.
Study visits:
Screening, baseline, week 2, month 3, month 6 and every 6 months thereafter. Information needed for the trial will be obtained as much as possible from visits taking place as part of routine clinical care.
Sample size:
Renal Lifecycle is designed as an endpoint driven trial and will finish when 468 primary study outcomes have occurred. The investigators have estimated a sample size of 1750-2000 patients.
Novel aspects:
A unique patient population with severe chronic kidney disease at very high risk of adverse outcomes for whom very few proven effective therapies exist. The initiation and efficacy of SGLT2 inhibitors, including dapagliflozin, has not been studied before in this population. However, SGLT2 inhibitors have the potential to be very effective and well tolerated which would imply a major advance in the pharmacotherapy of these patients.
When patients reach a renal endpoint, e.g. start or chronic dialysis or receiving a kidney transplantation, study medication will not be stopped as customary in many other trials in nephrology, but continued in the new phase of their "renal lifecycle", hence the name of the trial.
Sub studies:
Cardiac MRI sub-study The cardiac MRI sub-study will evaluate the effect of dapagliflozin on cardiac remodelling, as compared to placebo, measured with indexed left ventricular mass (LVMi), an intermediate cardiovascular outcome, in 250 participants across all three groups of the Renal Lifecycle Trial (i.e. advanced CKD, dialysis, kidney transplant recipients). This will provide robust evidence on the mechanisms under-pinning the cardioprotective effects of SGLT2 inhibitors in this high-risk patient population.
Primary outcome: Difference in LVMi after 12 months dapagliflozin compared to placebo.
Secondary outcomes: Differences between intervention groups in the following parameters at 12 months post-randomization: non-indexed LVM; indexed left atrial volume; non-indexed left atrial volume; indexed left and right ventricular end diastolic volume; indexed left and right ventricular end systolic volume; left and right ejection fraction.
Echocardiography sub-study (STOP-HF-in-PD) The echocardiography sub-study (STOP-HF-in-PD) will evaluate the effect of dapagliflozin on cardiac function, as compared to placebo, measured by left ventricular global longitudinal strain (LV-GLS), in 100 participants with kidney failure treated with peritoneal dialysis (PD). This will provide additional evidence on the mechanisms underlying the cardiac effects of SGLT2i in patients with kidney failure. Furthermore, the LV-GLS-data will be related to measured CKD- and PD-associated mediators of heart failure (measured in serum, urine and peritoneal effluent). This will aid to determine their relevance in patients with kidney failure, as well as to define if and to what extent SGLT2i affect these mediators in patients with kidney failure.
Primary outcome: Difference in LV-GLS after 6 months dapagliflozin compared to placebo.
Secondary and exploratory objectives: Differences between dapagliflozin compared to placebo after 6 and 12 months post-randomization for: LV-GLS; E/e'-ratio; left atrial volume index; left atrial strain; tricuspid velocity; left ventricular ejection fraction; LVMi; Physical functioning (6 minute walking test and KCCQ-12); 24h urine volume; residual kidney function; average daily ultrafiltration volume; peritoneal glucose exposure; peritoneal membrane characteristics.
Combined Cardiac Imaging Sub-studies A subset of participants enrolled in the echocardiography sub-study will also participate in the cardiac MRI sub-study, allowing for a combined evaluation of both imaging modalities. The aim is to evaluate the use of echocardiography and cardiac MRI as a tool to identify patients at highest risk for heart failure and those who may benefit from SGLT2i-induced cardio-protection.
Secondary outcomes: Association between change in LV-GLS and change in LVMi from baseline to 12-months across intervention groups; association between change in LV-GLS at 6 months and change in LVMi at 12 months across intervention groups.
Cognitive sub-study Patients with chronic kidney disease (CKD) are at a much higher risk for developing cognitive impairment compared with the general population and both lower glomerular filtration rate and the presence of albuminuria are associated with its development. SGLT-2 inhibitor use is associated with better preservation of cognitive function in patients with CKD including those on hemodialysis and after kidney transplantation compared to placebo.Patients will be requested to perform the symbol digit modalities test at the same time as the questionnaires, i.e. at baseline (visit 2), visit 5 and visit 6, once every year after visit 6 and at EoT/EET.The primary outcome of the cognition sub study is the change over time in the number of correct answers in the symbol digit modalities test within 90 seconds.
Kidney metabolism substudy The primary aim of this substudy is to evaluate the effect of dapagliflozin 10 mg compared to a placebo on energy metabolism assessed by changes in the renal mitochondrial oxidative phosphorylation capacity in kidney transplant recipients participating in the RENAL LIFECYCLE Trial at the 3-month Follow-up Visit. Further aims of this substudy are to evaluate the differences in metabolic substrate preferences by measuring ketone body or acylcarnitine substrate-driven mitochondrial respiration following the randomization to dapagliflozin or placebo.
Differences in mitochondrial architecture including mitochondrial quantity and morphology will be assessed using electron microscopy.
3,090 studies on the registry are indexed under Renal Insufficiency, Chronic; 698 are open to participants now.
This study's planned enrollment of 1,750 is above the median of 73 across 2,157 interventional studies indexed under Renal Insufficiency, Chronic.
Browse Renal Insufficiency, Chronic studies →University Medical Center Groningen is the lead sponsor of 627 studies on the registry; 176 are open to participants now.
Counted across the registry records on this site, refreshed daily.
Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
In addition, to be eligible all subjects must meet all criteria below
Exclusion Criteria:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
GFR (glomerular filtration rate) is how much blood the kidneys filter each minute. It is usually estimated from a blood test — eGFR, by formulas such as CKD-EPI or MDRD — and some studies ask for it to be measured directly instead. Usually given in mL/min/1.73 m².
Check the method, the units and the minimum the study states. A value of 90 or above is in the normal-or-high range, but kidney damage can show in other tests too.
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
The study doctor’s estimate of how long someone is likely to live. Criteria use it so that people can stay in the study long enough for it to answer its question.
A weakened immune system. It can come from an illness, such as HIV or some blood cancers, or from medicines that turn the immune system down, for example after an organ transplant or for an autoimmune disease; steroids at higher doses count.
Read whether the line is about a condition or about medicines, and which medicines and doses it means.
Malignancy means cancer. Criteria about another or earlier malignancy ask whether you have had a different cancer, usually within a set number of years.
Some are commonly allowed, such as treated skin cancers other than melanoma and early cancers removed completely — check the exceptions this study lists.
An allergy, or another reaction of the immune system, to a substance. “Hypersensitivity to the study drug” means a known allergic reaction to it — not every side effect a medicine can have.
A score of how well the liver works in people with liver disease such as cirrhosis: class A is mild, B moderate and C severe.
GFR and eGFR (kidney filtering)
GFR (glomerular filtration rate) is how much blood the kidneys filter each minute. It is usually estimated from a blood test — eGFR, by formulas such as CKD-EPI or MDRD — and some studies ask for it to be measured directly instead. Usually given in mL/min/1.73 m².
Check the method, the units and the minimum the study states. A value of 90 or above is in the normal-or-high range, but kidney damage can show in other tests too.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Informed consent
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Life expectancy
The study doctor’s estimate of how long someone is likely to live. Criteria use it so that people can stay in the study long enough for it to answer its question.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Immunosuppression
A weakened immune system. It can come from an illness, such as HIV or some blood cancers, or from medicines that turn the immune system down, for example after an organ transplant or for an autoimmune disease; steroids at higher doses count.
Read whether the line is about a condition or about medicines, and which medicines and doses it means.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Cancer (malignancy)
Malignancy means cancer. Criteria about another or earlier malignancy ask whether you have had a different cancer, usually within a set number of years.
Some are commonly allowed, such as treated skin cancers other than melanoma and early cancers removed completely — check the exceptions this study lists.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Hypersensitivity
An allergy, or another reaction of the immune system, to a substance. “Hypersensitivity to the study drug” means a known allergic reaction to it — not every side effect a medicine can have.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Child-Pugh class
A score of how well the liver works in people with liver disease such as cirrhosis: class A is mild, B moderate and C severe.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Dapagliflozin 10 mg/day (oral)
Drug: Dapagliflozin 10 mg/day (oral)
Placebo 10 mg/day (oral)
Drug: Placebo
Drug page: Dapagliflozin
Patients take 10 mg dapagliflozin or matching placebo once daily in the morning
Also known as: Forxiga
Patients take 10 mg dapagliflozin or matching placebo once daily in the morning
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
Time frame: Total study duration intended to last 48 months
Number of participants to reach all-cause mortality
To determine if dapagliflozin is superior to placebo in reducing the incidence of all-cause mortality
Time frame: Total study duration intended to last 48 months
Incidence of hospitalization for heart failure
Incidence of hospitalization for heart failureTo determine if dapagliflozin is superior to placebo in reducing the incidence of heart failure
Time frame: Total study duration intended to last 48 months
Incidence of kidney failure (chronic dialysis, kidney transplantation or mortality due to kidney failure)
To determine if dapagliflozin is superior to placebo in reducing the incidence of kidney failure
Time frame: 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
To determine whether dapagliflozin is superior to placebo in reducing the incidence of the composite outcome in subgroups subgroups: advanced CKD i.e. an eGFR ≤30 mL/min/1.73m2, dialysis patients and transplant patients
Time frame: Total study duration intended to last 48 months
measuring Quality of life with the EQ-5D questionnaire
To determine whether dapagliflozin is superior to placebo in comparing the Quality of Life for all subgroups based on the EQ-5D questionnaire
Time frame: Total study duration intended to last 48 months
measuring Quality of life with the SF12 questionnaire
To determine whether dapagliflozin is superior to placebo in comparing the Quality of Life for all subgroups based onthe SF12 questionnaire
Time frame: 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
cost-effectiveness of SGLT2-inhibition in the overall study population as well as in the three subpopulations
Time frame: Total study duration intended to last 48 months
incidence of de-novo type 2 diabetes in patients without diabetes
To determine whether dapagliflozin is superior to placebo in reducing the incidence of de-novo type 2 diabetes
Time frame: Total study duration intended to last 48 months
Change in the eGFR slope
To determine whether dapagliflozin is superior to placebo in reducing the eGFR slope eGFR slope; for the dialysis subgroup slope residual kidney function will be calculated using the average of 24hr urinary creatinine and urea clearance values over time
Time frame: Total study duration intended to last 48 months
incidence of diuresis <200 ml/24hr in the dialysis subgroup
To determine whether dapagliflozin is superior to placebo in the incidence of diuresis \<200 ml/24hr in the dialysis subgroup for this purpose 24hr urine samples will be collected ≥2 times per year
Time frame: 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 with and without type 2 diabetes separately
To determine if dapagliflozin is superior to placebo in reducing the incidence of kidney failure with and without type 2 diabetes separately
Time frame: Total study duration intended to last 48 months
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Plan to share: No
From the registry record's own update history. This site started tracking changes on Sep 25, 2026; for anything earlier, see the record history on ClinicalTrials.gov ↗
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Studies of the drug tested here: Dapagliflozin
Renal Insufficiency, Chronic →
University Medical Center Groningen →