UMIN-CTR Clinical Trial

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	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 -EMBODY trial-
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
Scientific Title:Acronym	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 -EMBODY trial-
Region	Japan

Condition
Condition	Type 2 diabetes with acute myocardial infarction
Classification by specialty	Cardiology Endocrinology and Metabolism
Classification by malignancy	Others
Genomic information	NO

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	2
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	98

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
Institute	Nippon Medical School Hospital
Institute
Department

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
Secondary IDs	NO
Study ID_1
Org. issuing International ID_1
Study ID_2
Org. issuing International ID_2
IND to MHLW

Institutions
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
URL(English)	https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000034442