A Multicentre International Randomized Parallel Group Double-blind Placebo-controlled Clinical Trial of EMPAgliflozin Once Daily to Assess Cardio-renal Outcomes in Patients With Chronic KIDNEY Disease
Overview
- Phase
- Phase 3
- Intervention
- Empagliflozin
- Conditions
- Chronic Kidney Disease
- Sponsor
- Boehringer Ingelheim
- Enrollment
- 6609
- Locations
- 237
- Primary Endpoint
- Interventional Part: Time to First Occurrence of Kidney Disease Progression or Cardiovascular Death ('as Adjudicated')
- Status
- Completed
- Last Updated
- 9 months ago
Overview
Brief Summary
The primary aim of the study is to investigate the effect of empagliflozin on kidney disease progression or cardiovascular death versus placebo on top of standard of care in patients with pre-existing chronic kidney disease. After completion of the interventional part of the study (primary study completion) a subset of participants will be followed up in a post-trial observational (non-interventional) manner for cardio-renal outcomes (estimated study completion date).
Investigators
Eligibility Criteria
Inclusion Criteria
- •Age ≥18 years or at "full age" as required by local regulation
- •Evidence of chronic kidney disease at risk of kidney disease progression defined by at least 3 months before and at the time of Screening Visit
- •CKD-EPI eGFR ≥20 to \<45 mL/min/1.73m² or
- •CKD-EPI eGFR ≥45 to \<90 mL/min/1.73m² with urinary albumin:creatinine ratio ≥200 mg/g (or protein:creatinine ratio ≥300 mg/g);
- •Clinically appropriate doses of single agent RAS-inhibition with either ACEi or ARB unless such treatment is either not tolerated or not indicated
- •A local Investigator judges that the participant neither requires empagliflozin (or any other SGLT-2 or SGLT-1/2 inhibitor), nor that such treatment is inappropriate;
Exclusion Criteria
- •Currently receiving SGLT-2 or SGLT-1/2 inhibitor
- •Diabetes mellitus type 2 and prior atherosclerotic cardiovascular disease with an eGFR \>60 mL/min/1.73m2 at Screening
- •Receiving combined ACEi and ARB treatment
- •Maintenance dialysis, functioning kidney transplant, or scheduled living donor transplant
- •Polycystic kidney disease
- •Previous or scheduled bariatric surgery
- •Ketoacidosis in the past 5 years
- •Symptomatic hypotension, or systolic blood pressure \<90 or \>180 mmHg at Screening
- •ALT or AST \>3x ULN at Screening
- •Hypersensitivity to empagliflozin or other SGLT-2 inhibitor
Arms & Interventions
Empagliflozin 10 mg
Patients with evidence of chronic kidney disease (CKD) at risk of kidney disease progression, with or without diagnosed diabetes mellitus administered orally once daily 10 milligram (mg) film-coated tablets of empagliflozin.
Intervention: Empagliflozin
Placebo
Patients with evidence of chronic kidney disease (CKD) at risk of kidney disease progression, with or without diagnosed diabetes mellitus administered orally once daily film-coated tablets of placebo to match empagliflozin.
Intervention: Matching placebo
Outcomes
Primary Outcomes
Interventional Part: Time to First Occurrence of Kidney Disease Progression or Cardiovascular Death ('as Adjudicated')
Time Frame: From the day of randomisation to the day of the final follow-up visit in the interventional part of the trial, up to 1136 days.
Time to first occurrence of kidney disease progression (KDP) or cardiovascular death is reported as incidence rate of first occurrence of KDP or adjudicated cardiovascular death. Incidence rate= (Number of patients who experienced the event of first occurrence of KDP or cardiovascular death)\*100/(patient years at risk (pt-yrs at risk). pt-yrs at risk= sum of time at risk \[days\] over all patients in a treatment group / 365.25. Kidney disease progression was defined as: * end stage kidney disease (defined as the initiation of maintenance dialysis or receipt of a kidney transplant) OR * a sustained decline in estimated glomerular filtration rate (eGFR) to \<10 mL/min/1.73m\^2 OR * renal death OR * a sustained decline of ≥40% in eGFR from randomisation.
Overall Study: Time to the First Occurrence of Kidney Disease Progression or Cardiovascular Death ('as Adjudicated')
Time Frame: From the day of randomization in the interventional part of the trial until the individual day of end of study in the non-interventional part of the trial. Up to 1869 days.
Time to first occurrence of kidney disease progression (KDP) or cardiovascular death is reported as incidence of progression of kidney disease or death from cardiovascular causes in the interventional part of the trial and in the post-trial follow-up (non-interventional part). Incidence rate= (Number of patients who experienced the event of first occurrence of KDP or cardiovascular death)\*100/(patient years at risk (pt-yrs at risk). pt-yrs at risk= sum of time at risk \[days\] over all patients in a treatment group / 365.25. Kidney disease progression was defined as: * a sustained decline in eGFR to less than 10 mL/min/1.73m\^2 OR * renal death OR * sustained decline of more than 40% in eGFR from randomization.
Secondary Outcomes
- Key Secondary Endpoint: Interventional Part - Time to First Hospitalization for Heart Failure ('as Adjudicated') or Cardiovascular Death ('as Adjudicated')(From the day of randomisation to the day of the final follow-up visit of the interventional part, up to 1140 days.)
- Key Secondary Endpoint: Interventional Part - Time to Occurrences of All-cause Hospitalizations (First and Recurrent Combined)(From the day of randomisation to the day of the final follow-up visit of the interventional part, up to 1140 days.)
- Key Secondary Endpoint: Interventional Part - Time to Death From Any Cause ('as Adjudicated')(From the day of randomisation to the day of the final follow-up visit in the interventional part of the trial, up to 1140 days.)
- Interventional Part: Time to First Occurrence of Kidney Disease Progression(From the day of randomisation to the day of the final follow-up visit of the interventional part, up to 1136 days.)
- Interventional Part: Time to Cardiovascular Death ('as Adjudicated')(From the day of randomisation to the day of the final follow-up visit of the interventional part, up to 1140 days.)
- Interventional Part: Time to First Occurrence Cardiovascular Death ('as Adjudicated') or End Stage Kidney Disease (ESKD)(From the day of randomization to the day of the final follow-up visit in the interventional part of the trial, up to 1140 days.)
- Overall Study: Time to First Occurrence of Kidney Disease Progression(From the day of randomization in the interventional part of the trial until the individual day of end of study in the non-interventional part of the trial. Up to 1869 days.)
- Overall Study: Time to First Occurrence of Death From Any Cause or ESKD(From the day of randomization in the interventional part of the trial until the individual day of end of study in the non-interventional part of the trial. Up to 1869 days.)
- Overall Study: Time to First Occurrence of ESKD(From the day of randomization in the interventional part of the trial until the individual day of end of study in the non-interventional part of the trial. Up to 1869 days.)
- Body Composition Measurement Sub-study: Mean Absolute Fluid Overload, Averaged Over Time(MMRM included measurements at baseline, 2 months, and 18 months.)
- Magnetic Resonance Imaging Sub-study: Kidney Cortical T1 Mapping as Measured by Modified Look-Locker Inversion Recovery (MOLLI) at 18 Months(At 18 months.)