UMIN-CTR Clinical Trial

Basic information
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
Condition	Compensated Heart Failure
Classification by specialty	Cardiology
Classification by malignancy	Others
Genomic information	NO

Objectives
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

Assessment
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

Base
Study type	Interventional

Study design
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

Intervention
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

Eligibility
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

Research contact person
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

Public contact
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

Sponsor
Institute	Nippon Medical School Chiba Hokusoh Hospital
Institute
Department

Funding Source
Organization	Ourselves
Organization
Division
Category of Funding Organization	Other
Nationality of Funding Organization

Other related organizations
Co-sponsor
Name of secondary funder(s)

IRB Contact (For public release)
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
Secondary IDs	NO
Study ID_1
Org. issuing International ID_1
Study ID_2
Org. issuing International ID_2
IND to MHLW

Institutions
Institutions

Other administrative information
Date of disclosure of the study information	2020 Year 05 Month 10 Day

Related information
URL releasing protocol
Publication of results	Published

Result
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

Progress
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
Other related information

Management information
Registered date	2020 Year 05 Month 10 Day
Last modified on	2020 Year 11 Month 16 Day

Link to view the page
URL(English)	https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000046042

Research Plan
Registered date	File name

Research case data specifications
Registered date	File name

Research case data
Registered date	File name

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