5. Hypothesis
▪ Clinical Question
▪ In individuals with acute heart failure, can empagliflozin benefit patients with
CKD and CVD outcome in patients with or without diabetes
▪ Hypothesis Empagliflozin can benefits in the setting
6. Introduction
▪ Established facts for SGLT2i till now before this trial is
▪ Oral hypoglycemic agent
▪ Decrease CKD progression in patients with type 2 diabetes malitas
▪ Have mortality benefit and decrease hospitalization and cardiovascular events
in a patient with or with out T2DM
7. BACKGROUND
▪ Since effect of SGLT2i Have been widely recognized in CKD and in
setting of acute, chronic heart failure
▪ How SGLt2i journey started
10. Several trials have been completed or are ongoing in
a range of patients with CKD, with and without T2D
2018 2019 2020 2021 2022 2023 2024
CREDENCE*†1
(canagliflozin)
FIDELIO-DKD*3,4
(finerenone)
FIGARO-DKD‡4,5
(finerenone)
DAPA-CKD*†2
(dapagliflozin)
EMPA-KIDNEY*§6,7
(empagliflozin)
FLOW*8
(semaglutide)
T2D T2D T2D T2D Non-DM T2D
T2D Non-DM
Q4 Q2 Q3 Q3
10
11. DAPA-CKD and CREDENCE showed beneficial effects on
CV and kidney outcomes in patients with CKD or DKD
CREDENCE2
DAPA-CKD1
Composite kidney/CV outcome*
Composite kidney outcome†
CV death or HHF
All-cause mortality
HR 0.61 (0.51, 0.72),
p<0.001
HR 0.56 (0.45, 0.68),
p<0.0001
HR 0.71 (0.55, 0.92),
p=0.009
HR 0.69 (0.53, 0.88),
p=0.004
HR 0.70 (0.59–0.82),
p<0.001
HR 0.66 (0.53–0.81),
p<0.001
HR 0.69 (0.57–0.83),
p<0.001
HR 0.83 (0.68–1.02),
p=NR
11
12. Persistent albuminuria categories
Description and range
A1 A2 A3
Normal to mildly
increased
Moderately
increased
Severely
increased
<30 mg/g
<3 mg/mmol
30–300 mg/g
3–30 mg/mmol
>300 mg/g
>30 mg/mmol
GFR
categories
(ml/min/1.73
m
2
)
Description
and
range
G1 Normal or high ≥90
G2 Mildly decreased 60–89
G3a
Mildly to moderately
decreased
45–59
G3b
Moderately to
severely decreased
30–44
G4 Severely decreased 15–29
G5 Kidney failure <15
*If no other markers of kidney disease, no CKD
GFR, glomerular filtration rate; eGFR, estimated glomerular filtration rate; UACR, urine albumin-to-creatinine ratio. 1. Perkovic V
et al. N Engl J Med 2019; DOI: 10.1056/NEJMoa1811744; 2. Heerspink H et al. Nephrol Dial Transplant 2020; doi:
DAPA-CKD and CREDENCE only included patients with
overt albuminuria (UACR ≥200 mg/g)1,2
Prognosis of CKD by GFR and albuminuria categories3
CREDENCE population1
Patients with DKD and eGFR
≥30 to <90 ml/min/1.73 m2
and UACR >300 mg/g
DAPA-CKD population2
Patients with or without DKD
and eGFR >25 to <75
ml/min/1.73 m2 and UACR
≥200 mg/g to ≤5000 mg/g
12
13. *Single RAAS inhibition in clinical appropriate dose and management of CV risk factors and other existing comorbidities,
including hypertension and diabetes
RAAS, renin-angiotensin-aldosteron system
Trial design
Placebo qd + standard of care*
Randomisation (1:1)
Double-blind
N=~6000
Every 6 months thereafter,
until required number of
events has accrued
0
Placebo run-in
Follow-up
visit
Empagliflozin 10 mg qd + standard of care*
Screening
EMPA-KIDNEY is a multinational, randomised, double-blind, placebo-controlled phase III study of
patients with chronic kidney disease with and without diabetes mellitus
2 months
30–48 months
Event driven: Study continues until ≥1070 primary outcome events accrue 1 month
-2 2 6 12 +1
Months
End of treatment
13
14.
15. Key inclusion and exclusion criteria
Key exclusion criteria
• Currently receiving an SGLT2 or SGLT1/2 inhibitor
• T2D and prior atherosclerotic CV disease
with eGFR >60 ml/min/1.73 m2
• Receiving dual RAAS inhibition (two of ACEi,
ARB, DRI)
• Any intravenous immunosuppression therapy in the
last 3 months; or anyone currently on >45 mg
prednisolone (or equivalent)
• Maintenance dialysis, functioning kidney transplant, or
scheduled living donor transplant
• Polycystic kidney disease
• Type 1 diabetes mellitus
Key inclusion criteria
• Age ≥18 years or at “full age” as required by
local regulation
• Evidence of CKD at risk of kidney disease progression
defined by ≥3 months before and at
the time of screening visit
– eGFR ≥20 to <45 ml/min/1.73 m2, or
– eGFR ≥45 to <90 ml/min/1.73 m2 with
UACR ≥200 mg/g
• Clinically appropriate doses of single-agent RAAS
inhibition with either ACEi or ARB unless either not
tolerated or not indicated
• Neither requires an SGLT2 or SGLT1/2 inhibitor, nor that
such treatment is inappropriate
15
16. *If no other markers of kidney disease, no CKD. GFR, glomerular filtration rate; eGFR, estimated glomerular filtration rate; UACR, urine albumin-to-creatinine ratio. 1.
ClinicalTrials.gov. NCT03594110 (accessed July 2020); 2. Kidney Disease: Improving Global Outcomes (KDIGO) CKD Work Group. Kidney Int Suppl 2020;98:S1; 3.
Perkovic V et al. N Engl J Med 2019; doi: 10.1056/NEJMoa1811744; 4. Heerspink H et al. Nephrol Dial Transplant 2020; doi: 10.1093/ndt/gfz290
EMPA-KIDNEY enrols a CKD population with a broad range of GFR,
with and without albuminuria1
Prognosis of CKD by GFR and albuminuria categories2
Persistent albuminuria categories
Description and range
A1 A2 A3
Normal to mildly
increased
Moderately
increased
Severely
increased
<30 mg/g
<3 mg/mmol
30–300 mg/g
3–30 mg/mmol
>300 mg/g
>30 mg/mmol
GFR
categories
(ml/min/1.73
m
2
)
Description
and
range
G1 Normal or high ≥90
G2 Mildly decreased 60–89
G3a
Mildly to moderately
decreased
45–59
G3b
Moderately to
severely decreased
30–44
G4 Severely decreased 15–29
G5 Kidney failure <15
CREDENCE population3
Patients with DKD and eGFR
≥30 to <90 ml/min/1.73 m2
and UACR >300 mg/g
DAPA-CKD population4
Patients with or without DKD
and eGFR >25 to <75
ml/min/1.73 m2 and UACR
≥200 mg/g to ≤5000 mg/g
EMPA-KIDNEY population1
Patients with or without DKD and
eGFR ≥20 to <45 ml/min/1.73 m2
or
eGFR ≥45 to <90 ml/min/1.73 m2
and UACR ≥200 mg/g
16
17. The list of pre-specified endpoints shown here is not exhaustive. Please refer to ClinicalTrials.gov for the totality of endpoints
*CDISC guideline: renal death is a death determined to be caused by renal failure (eGFR <15 ml/min/1.73 m2), with no other cause of death indicated
†More endpoints than the key secondary endpoints listed here are pre-specified
eGFR, estimated glomerular filtration rate; ESKD, end-stage kidney disease; HHF, hospitalisation for heart failure; CDISC: Clinical Data Interchange Standards Consortium
Primary composite and secondary outcomes
CV death Kidney disease progression
Primary cardio-renal composite outcome
Clinical outcomes
ESKD defined as
• Initiation of chronic dialysis
• Kidney transplant
Renal death*
eGFR-based outcomes
Kidney function loss defined as
• Sustained ≥40% eGFR decline
• Sustained eGFR
<10 ml/min/1.73 m2
Key secondary endpoints†
1. HHF or CV death
2. All-cause hospitalisation
3. All-cause mortality
17
18. *event driven – trial will continue until 1070 events are accrued; anticipated dates are estimates
1. EMPA-KIDNEY study website available at: www.empakidney.org (accessed 16.December 2020); 2. ClinicalTrials.gov
NCT03594110 (accessed 03, November 2020)
Projected timeline
2019 2020 2021 2022
First patient
randomised1
5000th patient
randomised1
Anticipated
study completion2*
Total trial duration ~3.25 years
NOTE: Trial timelines
may be affected by
COVID-19 outbreak
18
19. During trial visit
every 6 months
▪ Patients Were Evaluated Periodically At Trial Visits
For
▪ Weight change
▪ Health Status
▪ Adverse Events.
▪ Vital Signs,
▪ Glycated Hemoglobin Level,
▪ eGFR,
▪ Quality of life
▪ Proteinuria
30. Strengths/Weaknesses
⚫Strengths
Study design
Large participants
Broad eligibility criteria
Appropriate statistical analysis
Baseline characteristics are similar
among all patients. with OGDMT
And RAAS blockade
Similar use of medications to
manage other health conditions
⚫Weaknesses
Study duration,
Not reaching cardiovascular outcome as
expected
Discontinuation of trial
