UMIN-CTR Clinical Trial

Unique ID issued by UMIN	UMIN000030158
Receipt number	R000034442
Scientific Title	Effect of Empagliflozin versus placebo on cardiac sympathetic activity in acute myocardial infarction patients with type 2 diabetes mellitus: Multi-Center placebo-controlled Double-Blind Randomized Trial
Date of disclosure of the study information	2017/12/01
Last modified on	2019/12/10 13:39:37

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Basic information

Public title

Effect of Empagliflozin versus placebo on cardiac sympathetic activity in acute myocardial infarction patients with type 2 diabetes mellitus: Multi-Center placebo-controlled Double-Blind Randomized Trial

Acronym

Scientific Title

Scientific Title:Acronym

Region

Japan

Condition

Type 2 diabetes with acute myocardial infarction

Classification by specialty

Cardiology Endocrinology and Metabolism

Classification by malignancy

Others

Genomic information

Objectives

Narrative objectives1

I: Primary objective is to investigate that empagliflozin add-on to the conventional therapy improves heart rate variability (HRV) assessed by Ambulatory ECG (SCM-8000), a surrogate maker of lethal ventricular tachyarrhythmias in comparison with placebo.

II: Secondary objectives are to evaluate the change from baseline in the following measurements after empagliflozin treatment add on to conventional therapy in comparison with placebo.
1) T-wave alternans (TWA), late potential (LP), and heart rate turbulence (HRT) assessed by Ambulatory ECG (SCM-8000)
2) Cardiac sympathetic activity assessed by ¹²³I-MIBG Scintigraphy
3) Blood pressure, body weight, BMI, HbA1c (NGSP), fasting plasma glucose, Serum lipids [TC, LDL-C (direct method), HDL-C, TG, and non-HDL-C], AST, ALT, gamma-GTP, UA, serum creatinine, eGFR (adjusted value), NT-pro BNP, serum ketone body (venous blood), and blood count (RBC, WBC, hemoglobin, hematocrit, and platelet), cystatin C, hs-CRP
4) Body fluid volume assessed by InBody

Basic objectives2

Safety,Efficacy

Basic objectives -Others

Trial characteristics_1

Trial characteristics_2

Developmental phase

Assessment

Primary outcomes

To compare the change from baseline of HRV at 24 weeks treatment between two groups
1) Time domain analysis [mean RR interval for 24 h (mean NN), standard deviation of normal RR intervals (SDNN), standard deviation of all 5-min mean normal RR intervals (SDANN), square root of the mean of the sum of the squares of differences between adjacent RR intervals (r-MSSD), and percentage of adjacent RR intervals differing > 50 ms (pNN50)]
2) Frequency domain analysis: [Total power (TP, 0-0.4 Hz), high-frequency (HF, 0.15-0.4 Hz), low-frequency (LF, 0.04-0.15 Hz), and sympathovagal balance (LF/HF ratio)]

Key secondary outcomes

To compare the change from baseline in the clinical tests listed in the followings at 24 weeks treatment between two groups
1) TWA, LP, and HRT assessed by Ambulatory ECG (SCM-8000)
2) Cardiac sympathetic activity assessed by ¹²³I-MIBG Scintigraphy
3) Blood pressure, body weight, BMI, HbA1c (NGSP), fasting plasma glucose, Serum lipids [TC, LDL-C (direct method), HDL-C, TG, and non-HDL-C], AST, ALT, gamma-GTP, UA, serum creatinine, eGFR (adjusted value), NT-pro BNP, serum ketone body (venous blood), and blood count (RBC, WBC, hemoglobin, hematocrit, and platelet), cystatin C, hs-CRP
4) Body fluid volume assessed by InBody

Base

Study type

Interventional

Study design

Basic design

Parallel

Randomization

Randomized

Randomization unit

Individual

Blinding

Double blind -all involved are blinded

Control

Placebo

Stratification

Dynamic allocation

Institution consideration

Blocking

Concealment

Intervention

No. of arms

Purpose of intervention

Treatment

Type of intervention

Medicine

Interventions/Control_1

Empagliflozin 10 mg is administered orally before or after breakfast once daily for 24 weeks, and initiation period of administration is 2 to 12 weeks after the onset of acute myocardial infarction.

Interventions/Control_2

Placebo is administered orally before or after breakfast once daily for 24 weeks, and initiation period of administration is 2 to 12 weeks after the onset of acute myocardial infarction.

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

20 years-old <=

Age-upper limit

Not applicable

Gender

Male and Female

Key inclusion criteria

1) 20 years or older at consent
2) Patients who meet the following items
- Subjects appropriately diagnosed as T2DM by the latest Japanese guideline
- Drug-naive subjects or taking single anti-diabetic agent
- T2DM patients who need to start, or are possibly changing or adding an anti-diabetic agent
3) Patients with acute myocardial infarction who can receive outpatient visits after discharge

Key exclusion criteria

1) Type 1 diabetes mellitus
2) Persistent atrial fibrillation
3) Insulin, glucagon-like peptide-1 analogue, or other SGLT2 inhibitors user
4) High dose of sulfonylurea (glimepiride > 2 mg, glibenclamide > 1.25 mg, gliclazide > 40 mg)
5) HbA1c >= 10%
6) History of diabetic ketoacidosis or diabetic coma within 3 months prior to the randomization
7) Renal dysfunction (eGFR < 45 mL/min/1.73m²)
8) Heart failure graded at NYHA functional class IV
9) Pregnancy or possible pregnancy and breast feeding
10) Lack of informed consent
11) Patients judged by the investigator to be ineligible for inclusion in this study
12) Contraindicated for administration of empagliflozin

Target sample size

Research contact person

Name of lead principal investigator

1st name Wataru

Middle name

Last name Shimizu

Organization

Nippon Medical School Hospital

Division name

Department of Cardiovascular Medicine

Zip code

113-8603

Address

1-1-5, Sendagi, Bunkyo-ku, Tokyo, Japan

TEL

03-3822-2131

Email

wshimizu@nms.ac.jp

Public contact

Name of contact person

1st name Yoshiaki

Middle name

Last name Kubota

Organization

Nippon Medical School Hospital

Division name

Department of Cardiovascular Medicine

Zip code

113-8603

Address

1-1-5, Sendagi, Bunkyo-ku, Tokyo, Japan

TEL

03-3822-2131

Homepage URL

Email

ykubota@nms.ac.jp

Sponsor or person

Institute

Nippon Medical School Hospital

Institute

Department

Personal name

Funding Source

Organization

Nippon Boehringer Ingelheim Co., Ltd.

Organization

Division

Category of Funding Organization

Profit organization

Nationality of Funding Organization

Other related organizations

Co-sponsor

Name of secondary funder(s)

Eli Lilly and Company

IRB Contact (For public release)

Organization

Nippon Medical School Hospital Institutional Review Board

Address

1-1-5, Sendagi, Bunkyo-ku, Tokyo, Japan

Tel

03-3822-2131

Email

t-takase@nms.ac.jp

Secondary IDs

Study ID_1

Org. issuing International ID_1

Study ID_2

Org. issuing International ID_2

IND to MHLW

Institutions

日本医科大学付属病院（東京都）、日本医科大学千葉北総病院（千葉県）、日本医科大学多摩永山病院（東京都）、日本医科大学武蔵小杉病院（神奈川県）、静岡医療センター（静岡県）

Other administrative information

Date of disclosure of the study information

2017 Year 12 Month 01 Day

Related information

URL releasing protocol

Publication of results

Unpublished

Result

URL related to results and publications

Number of participants that the trial has enrolled

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

Completed

Date of protocol fixation

2017 Year 11 Month 01 Day

Date of IRB

2017 Year 07 Month 28 Day

Anticipated trial start date

2018 Year 02 Month 01 Day

Last follow-up date

2019 Year 10 Month 31 Day

Date of closure to data entry

Date trial data considered complete

Date analysis concluded

Other

Other related information

Registration in UMIN was closed and have been shifted to jRCT.
The number of clinical trial plan: jRCTs031180185

Management information

Registered date

2017 Year 11 Month 28 Day

Last modified on

2019 Year 12 Month 10 Day

Link to view the page

Value
https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000034442

Research Plan
Registered date	File name

Research case data specifications
Registered date	File name

Research case data
Registered date	File name