UMIN-CTR Clinical Trial

Public title

Role of Empagliflozin in Patients with Compensated Heart Failure Complicated by Diabetes Mellitus

Acronym

Sodium-glucose cotransporter-2 inhibitor in Heart Failure

Scientific Title

The Administration of Empagliflozin Can Prevent the Exacerbation of Renal Tubular Injury in Patients with Compensated Heart Failure Complicated by Diabetes Mellitus

Scientific Title:Acronym

sodium-glucose cotransporter-2 inhibitor in Patients with Compensated Heart Failure Complicated by Diabetes Mellitus

Region

Japan

Condition

Compensated Heart Failure

Classification by specialty

Cardiology

Classification by malignancy

Others

Genomic information

NO

Narrative objectives1

One of the effects exerted by SGLT2 inhibitors is a diuretic effect, induced by increasing the urinary glucose content. We therefore posed the clinical question of whether or not the dose of loop diuretics can be reduced in HF patients being treated with an SGLT2 inhibitor. We hypothesized that an SGLT2 inhibitor would help prevent renal dysfunction, particularly renal tubular injury, by enabling a reduction in the dosage of loop diuretics in HF patients. To test this hypothesis, we conducted a multicenter center prospective study in patients with diabetic compensated HF who were already being treated with loop diuretics.

Basic objectives2

Safety,Efficacy

Basic objectives -Others

Trial characteristics_1

Trial characteristics_2

Developmental phase

Primary outcomes

Time-dependent changes in the laboratory and urinary data (including cardiac biomarkers and urinary biomarkers) as well as medication for DM and for HF (including the dose of loop diuretics) were evaluated between the start date and six months in both the empagliflozin and control groups.
The urine and blood samples were collected on the day when consent was obtained (start date) and at the follow-up examination after six months (six months). The serum levels of heart-type fatty acid-binding protein (HFABP) and brain-type natriuretic peptide (BNP) were measured as cardiac biomarkers. In addition, the neutrophil gelatinase-associated lipocalin (NGAL), urine liver fatty acid-binding protein (LFABP), and acetyl-beta-D glucosaminidase (NAG) excretion was also measured as urinary renal tubular biomarkers. These urine and serum biomarkers were measured by the Special Reference Laboratory (SRL, Tokyo, Japan). The level of urinary LFABP was measured with an enzyme-linked immunosorbent assay (ELISA) using a human LFABP ELISA kit (Kyowa Medex Co., Tokyo, Japan). The level of urinary NGAL was measured using the NGAL ELISA Kit (R&D Systems, Inc., Minneapolis, MN, USA). The lower and upper limits of detection for the urinary NGAL concentration were 4 and 500 pg/ml, respectively, and the lower limit for the u-LFABP was 2.9 pg/ml.

Key secondary outcomes

Study type

Interventional

Basic design

Cross-over

Randomization

Randomized

Randomization unit

Individual

Blinding

Open -but assessor(s) are blinded

Control

No treatment

Stratification

Dynamic allocation

Institution consideration

Blocking

Concealment

No. of arms

2

Purpose of intervention

Treatment

Type of intervention

Medicine

Interventions/Control_1

The presence of empagliflozin administration.
Empagliflozin was started at 10 mg per day and increased to 25 mg per day after the first evaluation of tolerability. There were no limitations on HF therapy except for empagliflozin use, and the treatment strategy was determined by each patient's doctor. Two patients in the empagliflozin group dropped out during the six-month follow-up.

Interventions/Control_2

The presence absence of empagliflozin administration.
The patients in control group were not administrated SGLT2 inhibitor within 6 month.
There were no limitations on HF therapy except for empagliflozin use, and the treatment strategy was determined by each patient's doctor. Two patients in the empagliflozin group dropped out during the six-month follow-up.

Interventions/Control_3

Interventions/Control_4

Interventions/Control_5

Interventions/Control_6

Interventions/Control_7

Interventions/Control_8

Interventions/Control_9

Interventions/Control_10

Age-lower limit

Not applicable

Age-upper limit

Not applicable

Gender

Male and Female

Key inclusion criteria

Diabetic compensated HF patients who visited the outpatient clinics were prospectively enrolled in this study.
HF was diagnosed by the treating physician at the outpatient clinic according to the European Society of Cardiology (ESC) guidelines for the diagnosis of HF. Enrolled patients were diagnosed chronic HF or have a history of acute HF at the enrolled date and were assessed as having compensated HF. All patients were administered loop diuretics (furosemide and/or trasemide and/or azosemide) at the start date of the study.

Key exclusion criteria

The patients were excluded as follows;
1. History of the hypersensitivity to SGLT2 inhibitor
2. Diabetic coma
3. Severe infectious disease
4. The physician decided to be impossible to administrate the SGLT2 inhibitor
5. Did not obtain the informed consent.

Target sample size

60

Name of lead principal investigator

1st name	Akihiro
Middle name
Last name	Shirakabe

Organization

Nippon Medical School Chiba Hokusoh Hospital

Division name

Division of Intensive Care Unit

Zip code

270-1694

Address

1715 Kamagari, Inzai, Chiba 270-1694, Japan

TEL

0476-99-1111

Email

s6042@nms.ac.jp

Name of contact person

1st name	Akihiro
Middle name
Last name	Shitakabe

Organization

Nippon Medical School Chiba Hokusoh Hospital

Division name

Division of Intensive Care Unit

Zip code

270-1694

Address

1715 Kamagari, Inzai, Chiba 270-1694, Japan

TEL

0476-99-1111

Homepage URL

Email

s6042@nms.ac.jp

Institute

Nippon Medical School Chiba Hokusoh Hospital

Institute

Department

Personal name

Organization

Ourselves

Organization

Division

Category of Funding Organization

Other

Nationality of Funding Organization

Co-sponsor

Name of secondary funder(s)

Organization

the institutional review board of Nippon Medical School Chiba Hokusoh Hospital

Address

1715 Kamagari, Inzai, Chiba 270-1694, Japan

Tel

0476-99-1111

Email

araraki@nms.ac.jp

Secondary IDs

NO

Study ID_1

Org. issuing International ID_1

Study ID_2

Org. issuing International ID_2

IND to MHLW

Institutions

Date of disclosure of the study information

2020

Year

05

Month

10

Day

URL releasing protocol

Publication of results

Published

URL related to results and publications

Number of participants that the trial has enrolled

60

Results

Results date posted

Results Delayed

Results Delay Reason

Date of the first journal publication of results

Baseline Characteristics

Participant flow

Adverse events

Outcome measures

Plan to share IPD

IPD sharing Plan description

Recruitment status

Main results already published

Date of protocol fixation

2018

Year

07

Month

31

Day

Date of IRB

2018

Year

07

Month

02

Day

Anticipated trial start date

2018

Year

08

Month

15

Day

Last follow-up date

2020

Year

03

Month

31

Day

Date of closure to data entry

Date trial data considered complete

Date analysis concluded

Other related information

Registered date

2020

Year

05

Month

10

Day

Last modified on

2020

Year

11

Month

16

Day

Link to view the page

Value
https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000046042