EMPA-KIDNEY (The Study of Heart and Kidney Protection With Empagliflozin)

Boehringer Ingelheim6,609 enrolled

Overview

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).

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

DOUBLE

Enrollment

6,609

Conditions

Chronic Kidney Disease

Interventions

EmpagliflozinDRUG

Taken daily with or without food

Matching placeboDRUG

Taken daily with or without food

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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; Key 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 * Any intravenous immunosuppression therapy in last 3 months; or anyone currently on \>45 mg prednisolone (or equivalent) * Use of an investigational medicinal product in the 30 days prior to Screening visit * Known to be poorly compliant with clinic visits or prescribed medication * Medical history that might limit the individual's ability to take trial treatments for the duration of the study (e.g. severe respiratory disease; history of cancer or evidence of spread within last 4 years, other than non-melanoma skin cancer; or recent history of alcohol or substance misuse) * Current pregnancy, lactation or women of childbearing potential (WOCBP), unless using highly-effective contraception * Type 1 diabetes mellitus

Locations (240)

Outcomes

Primary Outcomes

Interventional Part: Time to First Occurrence of Kidney Disease Progression or Cardiovascular Death ('as Adjudicated')

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.

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.

Overall Study: Time to the First Occurrence of Kidney Disease Progression or Cardiovascular Death ('as Adjudicated')

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.

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.

Secondary Outcomes

Key Secondary Endpoint: Interventional Part - Time to First Hospitalization for Heart Failure ('as Adjudicated') or Cardiovascular Death ('as Adjudicated')

Data from ClinicalTrials.gov

This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.

Nephrology Consultants, LLC

Huntsville, Alabama, United States

Aventiv Research, Inc

Mesa, Arizona, United States

Southern California Permanente Medical Group

San Diego, California, United States

University of California Los Angeles

Sylmar, California, United States

University of California Los Angeles

Torrance, California, United States

Yale University School of Medicine

New Haven, Connecticut, United States

Chase Medical Research, LLC

Thomaston, Connecticut, United States

Midland Florida Clinical Reearch Center, LLC

DeLand, Florida, United States

University of Florida

Gainesville, Florida, United States

East Coast Institute for Research, LLC

Jacksonville, Florida, United States

...and 230 more locations

Time to first hospitalization for heart failure ('as adjudicated') or cardiovascular death ('as adjudicated') is reported as incidence rate of first hospitalization for heart failure or cardiovascular death. Incidence rate= (Number of patients who experienced the event of first hospitalization for heart failure 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.

Time frame: 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)

Time to occurrences of all-cause hospitalizations is reported as total number of all-cause hospitalizations (first and recurrent combined).

Time frame: 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')

Time to death from any cause is reported as incidence rate of death from any cause. Incidence rate of death from any cause = (Number of patients who experienced the event of death from any cause) \* 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.

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 1140 days.

Interventional Part: Time to First Occurrence of Kidney Disease Progression

Time to first occurrence of kidney disease progression (KDP) is reported as incidence rate of first occurrence of kidney disease progression. Incidence rate of first occurrence of kidney disease progression= (Number of patients who experienced the event of first occurrence of kidney disease progression) \*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).

Time frame: 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')

Time to cardiovascular death ('as adjudicated') is reported as incidence rate of cardiovascular death. Incidence rate of cardiovascular death= (Number of patients who experienced the event of 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.

Time frame: 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)

Time to first occurrence of cardiovascular death ('as adjudicated') or end stage kidney disease is reported as incidence rate of first occurrence of cardiovascular death or end stage kidney disease (ESKD). Incidence rate of first occurrence cardiovascular death or end stage kidney disease (ESKD)= (Number of patients who experienced the event of first occurrence of cardiovascular death or end stage kidney disease (ESKD)) \*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. ESKD was defined as the initiation of maintenance dialysis or receipt of a kidney transplant.

Time frame: 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

The time to first occurrence of kidney disease progression in the interventional part of the trial and in the post-trial follow-up (non-interventional part) is reported as the incidence rate of first occurrence of kidney disease progression. Incidence rate of first occurrence of kidney disease progression= (Number of patients who experienced the event of first occurrence of kidney disease progression) \*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.

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.

Overall Study: Time to First Occurrence of Death From Any Cause or ESKD

Time to first occurrence of death from any cause or end stage kidney disease (ESKD) in the interventional part of the trial and in the post-trial follow-up (non-interventional part) is reported as incidence rate of first occurrence of death from any cause or ESKD. Incidence rate of first occurrence of death from any cause or end stage kidney disease (ESKD)= (Number of patients who experienced the event of first occurrence of death any cause or end stage kidney disease (ESKD)) \*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. ESKD was defined as the initiation of maintenance dialysis or receipt of a kidney transplant.

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.

Overall Study: Time to First Occurrence of ESKD

Time to first occurrence of end stage kidney disease (ESKD) in the interventional part of the trial and in the post-trial follow-up (non-interventional part) is reported as incidence rate of first occurrence of ESKD. Incidence rate of first occurrence of end stage kidney disease (ESKD)= (Number of patients who experienced the event of first occurrence of ESKD) \*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. ESKD was defined as the initiation of maintenance dialysis or receipt of a kidney transplant.

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.

Body Composition Measurement Sub-study: Mean Absolute Fluid Overload, Averaged Over Time

Mean absolute fluid overload averaged over time in the body composition measurement sub-study. Fluid overload or overhydration was measured using bioimpedance spectroscopy which derives the amount of water in liters (L) in the adipose tissue and lean mass tissues and computed as the difference between expected (based upon weight and body composition) versus measured extracellular water volume, with positive values representing excess fluid. A mixed model of repeated measures (MMRM) with terms for baseline, age, sex, screening diabetes status, local screening eGFR, local screening UACR, treatment, treatment-by-time interaction and baseline-by-time interaction was used for the analysis. The weighted mean of the values at 2 and 18 months.

Time frame: 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

Kidney cortical T1 mapping using the modified Look-Locker inversion recovery (MOLLI) measured by magnetic resonance imaging (MRI) in the placebo and empagliflozin groups. A linear regression with terms for age, sex, screening diabetes status, local screening eGFR, local screening UACR was used in the analysis.

Time frame: At 18 months.