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 (EMPA-KIDNEY)

Study type

• Study topic:
  Human medicinal product

  Disease /health condition
• Study type:
  Clinical trial
• Scope of the study:
  Assessment of risk minimisation measure implementation or effectiveness

  Effectiveness study (incl. comparative)
• Data collection methods:
  Primary data collection

Clinical trials

• Clinical trial phase:
  Therapeutic confirmatory (Phase III)
• Clinical trial randomisation:
  Randomised clinical trial

Study drug and medical condition

• Study drug International non-proprietary name (INN) or common name:
  EMPAGLIFLOZIN
• Medical condition to be studied:
  Chronic kidney disease

Population studied

• Short description of the study population:
  Patients with pre-existing chronic kidney disease (at least one-third with diabetes and one-third without diabetes) treated with empagliflozin and matching placebo on top of standard of care. ; Inclusion criteria:; Evidence of progressive CKD at risk of kidney disease progression is defined on the basis of local laboratory results recorded at least 3 months before and at the time of the Screening visit, and requires that:; • CKD-EPI eGFR ≥20 <45 mL/min/1.73m²; or; • CKD-EPI eGFR ≥45 <90 mL/min/1.73m2 with urinary albumin: creatinine ratio ≥200 mg/g (or protein: creatinine ratio ≥300 mg/g); ; 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 ARBf 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
• Age groups:
  Adults (18 to < 46 years)

  Adults (46 to < 65 years)

  Adults (65 to < 75 years)

  Adults (75 to < 85 years)

  Adults (85 years and over)
• Special population of interest:
  Renal impaired
• Estimated number of subjects:
  6000

Study design details

• Main study objective:
  The primary objective 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
• Outcomes:
  Composite primary outcome: Time to first occurrence of (i) kidney disease progression (defined as ESKD, a sustained decline in eGFR to <10 mL/min/1.73m², renal death, or a sustained decline of ≥40% in eGFR from randomization) or (ii) Cardiovascular death. End Stage Kidney Disease (ESKD) is defined as the initiation of maintenance dialysis or receipt of a kidney transplant, 1. Time to first hospitalization for heart failure or cardiovascular death 2. Time to occurrences of all-cause hospitalizations (first and recurrent combined) 3. Time to death from any cause 4. Time to kidney disease progression 5. Time to cardiovascular death 6. Time to cardiovascular death or end-stage kidney disease
• Data analysis plan:
  For the time-to-event analyses survival analytic methods will be used to evaluate the time to the first event during the entire trial period. For each categorical outcome, Cox proportional hazards regression adjusted for age, sex, prior diabetes, eGFR, urinary albumin:creatinine ratio, and region will be used to estimate the hazard ratio comparing all those allocated to active empagliflozin with all those allocated to placebo. Estimates of the hazard ratio will be shown with 95% confidence intervals. For the secondary outcome of all-cause hospitalisation, the analysis examined all events (i.e. not just the first event in each participant). Cumulative incidence function (CIF) and/or Kaplan Meier plots were produced where appropriate. For details refer to the Data Analysis Plan published on www.empakidney.org.

Documents

Study publications

Baigent C, Emberson J, Haynes R, Herrington WG, Judge P, Landray MJ, Mayne KJ, …

EMPA-Kidney Collaborative Group. Empagliflozin in patients with chronic kidney …

Herrington WG, Preiss D, Haynes R, Eynatten M, von Staplin N, Hauske SJ et al. …

"Design, recruitment, and baseline characteristics of the EMPA-KIDNEY trial." N…