臨床研究等提出・公開システム

Date of registration	Oct. 24, 2018
Last modified on	June. 23, 2025
Trial ID	jRCT2080224111

Scientific Title	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
Public Title	EMPA-KIDNEY

Completion Date or Terminated date	Dec. 23, 2022
Actual Enrolled Number	6609
Baseline Characteristics	[Age] mean (SD) Placebo (N: 3305): 63.3 (+-13.9) Empagliflozin 10 mg (N: 3304) :63.4 (+-13.9) [Sex] Placebo (N: 3305): - Female:1095, - Male:2210 Empagliflozin 10 mg (N: 3304): - Female:1097, - Male:2207 [Diagnosis] Patients with evidence of chronic kidney disease (CKD) at risk of kidney disease progression, with or without diagnosed diabetes mellitus. - Main criteria for inclusion: Evidence of CKD at risk of progression was defined on the basis of local laboratory results recorded at least 3 months before and at the time of the Screening visit, and required that: (a) CKD-EPI eGFR >=20 to <45 mL/min/ 1.73m2; or (b) CKD-EPI eGFR >=45 to <90 mL/min/ 1.73m2 with urinary albumin to creatinine ratio (UACR) >=200 mg/g (or protein to creatinine ratio >=300 mg/g) CKD-EPI eGFR values were estimated using the 2009 Chronic Kidney Disease Epidemiology Collaboration creatinine formula [R12-1392]. CKD-EPI, Chronic Kidney Disease Epidemiology Collaboration; eGFR, estimated glomerular filtration rate
Participant flow	- Number of subjects Started: 6609 (Placebo: 3305, Empagliflozin 10 mg: 3304) - Number of subjects Treated: 6609 (Placebo: 3305, Empagliflozin 10 mg: 3304) - Number of subjects Completed Study Treatment: 5006 (Placebo: 2457, Empagliflozin 10 mg: 2549) - Number of subjects Not Completed Study Treatment: 1603 (Placebo: 848, Empagliflozin 10 mg: 755) - Number of subjects analyzed: 6609 (Placebo: 3305, Empagliflozin 10 mg: 3304)
Adverse events	Safety results: Unless specified otherwise, safety was analysed based on the treated set (all participants who were dispensed study treatment) and included AEs up to 7 days after study treatment termination. For trial-specific safety endpoints (time to first occurrence of events), safety analyses were based on the randomised set (all randomised participants) and included data through trial completion. Adverse events: Empagliflozin and placebo groups had similar frequencies of participants with reported SAEs and prespecified non-serious AEs. The frequency of participants reported with AEs leading to discontinuation of study medication was also similar between treatment groups. The frequency of participants with investigator-defined drug-related AEs was low. The frequency of participants with SAEs overall was comparable between both groups. The frequency of participants with fatal AEs was similar in both groups. The frequencies of SAEs in each SOC were similar in the empagliflozin and placebo groups. SAEs and prespecified non-serious AEs were most frequently reported in the SOC metabolism and nutrition disorders, followed by infections and infestations, investigations, and renal and urinary disorders. On the PT level, the most frequently reported SAEs and prespecified non-serious AEs were gout (empagliflozin: 231 participants, 7.0%; placebo: 266 participants, 8.0%); acute kidney injury (empagliflozin: 93 participants, 2.8%; placebo: 117 participants, 3.5%); and coronavirus infection (empagliflozin: 98 participants, 3.0%; placebo: 107 participants, 3.2%). SAEs were most frequently reported in the SOCs renal and urinary disorders, and in infections and infestations. For SAEs, the most common PTs were acute kidney injury and coronavirus infection (values were the same as above). AESIs and specific AEs: The overall frequencies for liver injury, serious urinary tract infection, serious genital infection, severe hypoglycaemia, and urinary tract malignancy were comparable in the empagliflozin and placebo groups. Within the individual categories of AESIs and specific AEs, generally similar proportions ofparticipants in both treatment groups had serious AEs. Few AEs in any category of AESIs or specific AEs led to treatment discontinuation.
Primary Outcome Measures	- Primary and key secondary endpoints: The risk of kidney disease progression or CV death was significantly reduced [HR (95% CI) 0.72 (0.59, 0.89), p<0.0001] with empagliflozin treatment compared with placebo. The separation of the estimated cumulative incidence of kidney disease progression or CV death between empagliflozin and placebo became evident approximately 1 year after randomisation and was maintained over time. The results of the primary endpoint were consistent (interaction p-values >0.05) across the subgroups of key interest of baseline diabetes status and baseline eGFR, with the upper bound of the 95% CI for the HR for each subgroup <1. There was a trend towards increasing treatment effect in participants with higher levels of UACR at baseline (trend test interaction p-value = 0.0174). The risk of all-cause hospitalisations was significantly reduced with empagliflozin treatment compared with placebo. The separation of the estimated cumulative incidence of all-cause hospitalisations started shortly after randomisation and was maintained over time. The results were consistent (interaction p-values >0.05) across the 3 subgroups of key interest, with the upper bound of the 95% CI for the HR for each subgroup <1. The risks of all-cause death and HHF or CV death were not significantly reduced with empagliflozin compared with placebo. - Other secondary endpoints: Kidney disease progression occurred in a lower proportion of participants in the empagliflozin group (384 participants, 11.6%) than in the placebo group (504 participants, 15.2%). The risk of kidney disease progression was reduced with empagliflozin treatment vs. placebo (HR 0.71; 95% CI 0.62, 0.81). The separation of the cumulative incidence of kidney disease progression became evident approximately 1 year after randomisation and continued over time. CV death or ESKD occurred in a lower proportion of participants in the empagliflozin group (163 participants, 4.9%) than in the placebo group (217 participants, 6.6%). The risk of CV death or ESKD was reduced with empagliflozin treatment vs. placebo (HR 0.73; 95% CI 0.59, 0.89). The separation of the estimated cumulative incidence of CV death or ESKD between empagliflozin and placebo became evident approximately 1 year after randomisation and continued over time. Adjudicated CV death occurred in a low proportion of participants in both the empagliflozin group (59 participants, 1.8%) and the placebo group (69 participants, 2.1%); HR 0.84 (95% CI 0.60, 1.19; p = 0.3366).
Secondary Outcome Measures
Brief summary	Of the 6609 randomised participants, 6568 (99.4%) completed the trial, including 315 participants who died. Treatment with empagliflozin demonstrated a clinically meaningful cardio-renal benefit in a broad range of CKD patients. The overall benefit and risk assessment was positive for empagliflozin in a broad spectrum of patients with CKD.
Posting of journal publication
Date of the first journal publication of results	Oct. 25, 2018
URL hyperlink(s) related to results and publications	https://www.empakidney.org/downloads

Plan to share IPD	Yes
Plan description	After the study is completed and the primary manuscript is accepted for publishing, researchers can use this following link https://www.mystudywindow.com/msw/datasharing to request access to the clinical study documents regarding this study, and upon a signed "Document Sharing Agreement". Also, Researchers can use the following link https://www.mystudywindow.com/msw/datasharing to find information in order to request access to the clinical study data, for this and other listed studies, after the submission of a research proposal and according to the terms outlined in the website. The data shared are the raw clinical study data sets
URL link to protocol file(s)
Version of protocol file(s)	version: date:

Contact for Scientific Queries	Name
	Contact Name for Scientific Queries	University of Oxford
	Address	Richard Doll Building, Old Road Campus, Roosevelt Drive, Oxford OX3 7LF, UK
	Phone Number	44-0-1865-743868
	E-mail Address	cco.empakidney@ndph.ox.ac.uk

Contact for Public Queries	Name
	Contact Name for Public Queries	University of Oxford
	Address	Richard Doll Building, Old Road Campus, Roosevelt Drive, Oxford OX3 7LF, UK
	Phone Number	44-0-1865-743868
	E-mail Address	cco.empakidney@ndph.ox.ac.uk

Recruitment Status	completed

Date of First Enrolment		Aug. 26, 2019
Target Sample Size		6000
Study Type		Interventional
Study Design	Study Design	Randomized, parallel group, double-blind, placebo-controlled
Study Design	Objective	treatment purpose
Phase		3
Key inclusion & exclusion criteria	Inclusion Criteria	People with evidence of chronic kidney disease at risk of kidney disease progression, which 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: (a) CKD-EPI eGFR >=20 <45 mL/min/1.73m2; or (b) CKD-EPI eGFR >=45 <90 mL/min/1.73m2 with urinary albumin:creatinine ratio >=200 mg/g (or protein:creatinine ratio >=300 mg/g) Note: the number of participants with or without diabetes mellitus (of any type) will be at least one-third of each, and the number of participants with an eGFR>45 mL/min/1.73m2 limited to about one-third. The Steering Committee will monitor these proportions and will limit recruitment of particular categories of participant in whom sufficient numbers have already been screened or randomized.
	Exclusion Criteria	People fulfilling any of the following criteria will be excluded: (i) Currently receiving SGLT-2 or SGLT-1/2 inhibitor; (ii) Diabetes mellitus type 2 and prior atherosclerotic cardiovascular disease with an eGFR >60 mL/min/1.73m2 at Screening; (iii) Receiving combined ACEi and ARB treatment; (iv) Maintenance dialysis, functioning kidney transplant, or scheduled living donor transplant; (v) Polycystic kidney disease; (vi) Previous or scheduled bariatric surgery; (vii) Ketoacidosis in the past 5 years; (viii) Symptomatic hypotension, or systolic blood pressure <90 or >180 mmHg at Screening; (ix) ALT or AST >3x ULN at Screening; (x) Hypersensitivity to empagliflozin or other SGLT-2 inhibitor; (xi) Any intravenous immunosuppression therapy in last 3 months; or anyone currently on >45 mg prednisolone (or equivalent); (xii) Use of an investigational medicinal product in the 30 days prior to Screening visit; (xiii) Known to be poorly compliant with clinic visits or prescribed medication; (xiv) 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); (xv) Current pregnancy, lactation or women of childbearing potential (WOCBP), unless using highly-effective contraception. (xvi) Type 1 diabetes mellitus. In addition, individuals will be excluded at the Randomization visit if the participant: (i) Does not adhere to Run-in treatment; (ii) Is no longer willing to be randomized and followed for at least 3 years; (iii) Is considered by a local investigator not to be suitable for randomization; or (iv) Experiences ketoacidosis, heart attack, stroke, or hospitalization for heart failure, or hospitalization for urinary tract infection or acute kidney injury during Run-in.
	Minimum Age	20age old over
	Maximum Age	No limit
	Gender	Both
Health Condition or Problem Studied		Chronic kidney disease
Intervention(s)		investigational material(s) Generic name etc : empagliflozin INN of investigational material : Empagliflozin Therapeutic category code : 399 Agents affecting metabolism, n.e.c. Dosage and Administration for Investigational material : One tablet (10 mg) is to be taken daily with or without food. control material(s) Generic name etc : - INN of investigational material : - Therapeutic category code : --- Other Dosage and Administration for Investigational material : One tablet is to be taken daily with or without food.
Health Condition(s) Keyword
Intervention(s) Keyword
Health Condition(s) Code
Intervention(s) Code
Primary Outcome		efficacy The effects of allocation to empagliflozin versus placebo on the time to the 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 greater than or equal to 40% in eGFR from randomization); or (ii) Cardiovascular death.
Secondary Outcome		efficacy Key secondary outcomes: -Time to first hospitalization for heart failure or cardiovascular death -Time to occurrences of all-cause hospitalization (first and recurrent combined) -Time to death from any cause Other secondary outcomes: -Time to kidney disease progression -Time to cardiovascular death -Time to cardiovascular death or ESKD

Primary Sponsor	Boehringer Ingelheim(ICCC:PAREXEL International)
Secondary Sponsor	The Medical Research Council Population Health Research Unit at the University of Oxford is the academic lead of the trial and has been delegated the task of conducting and analyzing the trial

Name of Funding Organization	Boehringer Ingelheim (in collaboration with Eli Lilly and Company)
Name of Research Funding	-

Name of IRB	Okayama University Hospital IRB
Address of IRB	2-5-1, Shikata-cho, Kita-ku, Okayama-shi, Okayama, 700-8558, Japan
Phone Number of IRB	+81-86-235-7991
E-mail Address of IRB
Status of IRB Review	approved
Date of Approval by IRB	Jan. 21, 2019

Name of IRB	Kawasaki Medical School Hospital IRB
Address of IRB	Okayama
Phone Number of IRB	+81-86-462-1401
E-mail Address of IRB
Status of IRB Review	approved
Date of Approval by IRB	Jan. 21, 2019

Name of IRB	Tokai University, Faculty of Medicine, Hospital, IRB
Address of IRB	143, Shimokasuya, Isehara-shi, Kanagawa, 259-1193, Japan
Phone Number of IRB
E-mail Address of IRB
Status of IRB Review	approved
Date of Approval by IRB	Jan. 21, 2019

Name of IRB	Institutional Review Board of Kansai Electric Power Hospital
Address of IRB	2-1-7 Fukushima, Fukushima-Ku, Osaka-shi, Osaka, 553-0003, Japan
Phone Number of IRB
E-mail Address of IRB
Status of IRB Review	approved
Date of Approval by IRB	Jan. 21, 2019

Name of IRB	Niigata University Medical & Dental Hospital Institutional Review Board
Address of IRB	754, Ichibancho, Asahimachidori, Chuo-ku, Niigata-shi, Niigata, 951-8510, Japan
Phone Number of IRB
E-mail Address of IRB
Status of IRB Review	approved
Date of Approval by IRB	Jan. 21, 2019

Name of IRB	IRB of Tohoku University Hospital
Address of IRB	1-1 Seiryo-machi, Aoba-ku, Sendai, Miyagi, 980-8574 Japan
Phone Number of IRB	+81-22-717-7056
E-mail Address of IRB
Status of IRB Review	approved
Date of Approval by IRB	Jan. 21, 2019

Name of IRB	Kobe University Hospital IRB
Address of IRB	7-5-2 Kusunoki-cho, Chuo-ku, Kobe, Hyogo, 650-0017 Japan
Phone Number of IRB
E-mail Address of IRB
Status of IRB Review	approved
Date of Approval by IRB	Jan. 21, 2019

Name of IRB	Institutional Review Board of University of Tsukuba Hospital
Address of IRB	2-1-1 Amakubo, Tsukuba, Ibaraki, 305-8576, Japan
Phone Number of IRB
E-mail Address of IRB
Status of IRB Review	approved
Date of Approval by IRB	Jan. 21, 2019

Name of IRB	Mitsuyakai Maebashihirosegawa Clinic IRB
Address of IRB	2-10-9, Chiyodamachi, Maebashi-shi, Gunma, 371-0022, Japan
Phone Number of IRB
E-mail Address of IRB
Status of IRB Review	approved
Date of Approval by IRB	Jan. 21, 2019

Name of IRB	Ikeda Hospital IRB
Address of IRB	1830, Shimoharaigawa-cho, Kanoya-shi, Kagoshima 893-0024, Japan
Phone Number of IRB	+81-994-43-3434
E-mail Address of IRB
Status of IRB Review	approved
Date of Approval by IRB	Jan. 21, 2019

Name of IRB	Medical Incorporated Association Kyokuwakai Tokyo Station center building clinic IRB
Address of IRB	3-3-14,Nihonbashi,chuo-ku,Tokyo
Phone Number of IRB
E-mail Address of IRB
Status of IRB Review	approved
Date of Approval by IRB	Jan. 21, 2019

Name of IRB	Fukui Prefectural Hospital IRB
Address of IRB	2-8-1, Yotsui, Fukui-shi, Fukui, 910-8526, Japan
Phone Number of IRB
E-mail Address of IRB
Status of IRB Review	approved
Date of Approval by IRB	Jan. 21, 2019

Name of IRB	Fukuoka University Hospital Institutional Review Board
Address of IRB	7-45-1 Nanakuma, Jonan-ku, Fukuoka-shi, Fukuoka 814-0180, Japan
Phone Number of IRB	+81-92-801-1011
E-mail Address of IRB
Status of IRB Review	approved
Date of Approval by IRB	Jan. 21, 2019

Name of IRB	National Center for Global Health and Medicine IRB
Address of IRB	1-21-1 Toyama, Shinjuku-ku, Tokyo, 162-8555, Japan
Phone Number of IRB	+81-3-3202-7181
E-mail Address of IRB
Status of IRB Review	approved
Date of Approval by IRB	Jan. 21, 2019

Name of IRB	Shiga University of Medical Science Hospital
Address of IRB	Seta, Tsukinowa-cho, Otsu-shi, Shiga, 520-2192, Japan
Phone Number of IRB	+81-77-548-2222
E-mail Address of IRB
Status of IRB Review	approved
Date of Approval by IRB	Jan. 21, 2019

Name of IRB	Medical Corporation Kyosokai AMC Nishi-Umeda Clinic IRB
Address of IRB	Hotel Monterey Osaka Maruito Nishiumeda Building Office Floor 3F, 3-3-45 Umeda, Kita-ku, Osaka, 530-0001, Japan
Phone Number of IRB	+81-6-4797-5660
E-mail Address of IRB
Status of IRB Review	approved
Date of Approval by IRB	Jan. 21, 2019

Name of IRB	The University of Tokyo Hospital Institutional Review Board
Address of IRB	7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan
Phone Number of IRB	+81-3-5800-8743
E-mail Address of IRB
Status of IRB Review	approved
Date of Approval by IRB	Jan. 21, 2019

Name of IRB	Chubu Rosai Hospital Institutional Review Board
Address of IRB	1-10-6, Komei, Minato-ku, Nagoya, Aichi, 455-8530, Japan
Phone Number of IRB	+81-52-652-5511
E-mail Address of IRB
Status of IRB Review	approved
Date of Approval by IRB	Jan. 21, 2019

Name of IRB	Aichi Medical University Hospital Institutional Review Board
Address of IRB	1-1 Yazakokarimata, Nagakute,Aichi, 480-1195, Japan
Phone Number of IRB
E-mail Address of IRB
Status of IRB Review	approved
Date of Approval by IRB	Jan. 21, 2019

Secondary ID No.	NCT03594110
Name of Other Registries	ClinicalTrials.gov

Secondary ID No.	JapicCTI-184172
Name of Other Registries

Countries / Regions of Recruitment	Japan/Asia except Japan/North America/Europe

History of Changes

No	Publication date
11	June. 23, 2025	(this page)	Changes
10	Dec. 19, 2023	Detail	Changes
9	Sept. 29, 2023	Detail	Changes
8	Jan. 25, 2022	Detail	Changes
7	Jan. 20, 2022	Detail	Changes
6	Jan. 05, 2021	Detail	Changes
5	Jan. 07, 2020	Detail	Changes
4	Dec. 05, 2019	Detail	Changes
3	Dec. 17, 2018	Detail	Changes
2	Oct. 24, 2018	Detail	Changes
1	Oct. 24, 2018	Detail

List of change history