Effects of Empagliflozin on Left Ventricular Diastolic Function Compared to Usual Care in Type 2 Diabetics

• Register: ClinicalTrials.gov
• Last refreshed on: 26 April 2021
• Main ID: NCT02932436
• Date of registration: 12/10/2016
• Prospective Registration: No
• Primary sponsor: Johannes Gutenberg University Mainz
• Public title: Effects of Empagliflozin on Left Ventricular Diastolic Function Compared to Usual Care in Type 2 Diabetics EmDia
• Scientific title: A Phase IV, Single-center, Randomized, Double-blind, Placebo-controlled, Parallel Group Study on the Effects of Empagliflozin on Left Ventricular Diastolic Function Compared to Usual Care in Individuals With Type 2 Diabetes
• Date of first enrolment: October 10, 2016
• Target sample size: 144
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/show/NCT02932436
• Study type: Interventional
• Study design: Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor).
• Phase: Phase 4

Countries of recruitment

Germany

Contacts

• Name: Philipp Wild, MD, MSc
• Affiliation: Johannes Gutenberg University Mainz

Key inclusion & exclusion criteria

Inclusion Criteria:

Subjects meeting all of the following criteria at visit 0 (screening) will be considered
for admission to the trial:

- Diagnosis of type 2-diabetes mellitus with stable glucose-lowering background therapy
and/or dietetic treatment for at least 12 weeks

- In subjects without glucose-lowering background therapy: the application of Metformin
was considered to be unsuitable due to drug intolerance

- HbA1c level of =6.5% and =10.0% at visit 0 (screening) for subjects on antidiabetic
background therapy or HbA1c level of =6.5% and =9.0% for drug-naïve subjects with
dietetic treatment

- Diastolic cardiac dysfunction E/E' ratio =8 (2D-echocardiography)

- Age 18 - 84 years

- BMI = 45 kg/m² (Body Mass Index)

- For women: post-menopausal for more than 12 months without an alternative medical
cause can participate in the trial. Women with childbearing potential can only
participate, if they are surgically sterile or a negative pregnancy test (serum or
urine) is available at visit 1 and they are willing to practice highly effective birth
control method during trial. Reliable highly effective contraception comprises

- combined (estrogen and progesteron containing) hormonal contraception associated
with inhibition of ovulation (oral, intravaginal, transdermal)

- progesteron-only hormonal contraception associated with inhibition of ovaluation
(oral, injectable, implantable)

- intrauterine device (IUD)

- intrauterine hormone-releasing system (IUS)

- bilateral tubal occlusion

- vasectomised partner (provided that partner is the sole sexual partner and that
the vasectomised partner has received medical assessment of the surgical success)

- sexual abstinence (defined as refraining from heterosexual intercourse during the
entire period of risk associated with the study treatment. The reliability of
sexual abstinence needs to be evaluated in relation to the duration of the
clinical trial and the preferred and usual lifestyle of the subject.

- Ability of subject to understand nature, importance and individual consequences of
clinical trial

- Signed and dated informed consent of the subject must be available before start of any
specific trial procedures which is consistent with ICH-GCP guidelines and local
legislation

Exclusion Criteria:

Subjects presenting with any of the following criteria at visit 0 (screening) will not be
included in the trial:

- Pretreatment with empagliflozin or other SGLT2 inhibitor within the last 3 months

- Pretreatment with known inducers of UGT enzymes

- Uncontrolled hyperglycemia with a glucose level > 240 mg/dl (>13.3 mmol/L) after an
overnight fast

- Impaired renal function, defined as eGFR <45 ml/min/1.73 m² of body-surface-area

- End-stage renal failure or dialysis

- Severe hepatic dysfunction, defined by serum levels of either SGPT, SGOT, or alkaline
phosphatase above 3 x upper limit of normal (ULN)

- Acute urinary tract infection (UTI)

- Known acute genital infection (GI)

- Symptomatic hypotension

- Hematocrit above the upper limit of the reference range

- Hypoglycemic tendencies

- Severe PAD (Fontaine classification Stage IIb - IV)

- Medical history of cancer and/or treatment for cancer within the last 5 years,
subjects basalioma can be included in the study

- Medical history of pancreatitis or surgery on pancreas

- Known ketoacidosis (in the past)

- Acute febrile disease

- NYHA classification III - IV

- Pregnant and/or nursing women at visit 1 (baseline)

- Acute coronary syndrome, stroke or TIA within the last 2 months

- Planned cardiac surgery or angioplasty within 3 months

- Gastrointestinal surgeries that induce chronic malabsorption

- Blood dyscrasia or any disorders causing hemolysis or unstable Red Blood Cells (e.g.
malaria, babesiosis, hemolytic anemia)

- History of hypersensitivity to the investigational medicinal product or to any drug
with similar chemical structure or to any excipient present in the pharmaceutical form
of the investigational medicinal product

- Alcohol or drug abuse within the last 3 months that would interfere with trial
participation

- Medical or psychological conditions that would jeopardize an adequate and orderly
completion of the trial (at visit 0 (screening) or at visit 1 (baseline))

- Medical condition that does not allow enrollment in the trial at visit 1 (baseline)

- Current treatment with systemic steroids or change in dosage of thyroid hormones
within the last 6 weeks or any other uncontrolled endocrine disorder except type 2
diabetes mellitus

- Hereditary glucose intolerance, galactose intolerance, Lapp-lactase deficiency or
glucose-galactose-malabsorption

- Intake of an investigational drug in another trial within 30 days prior to intake of
study medication in this trial or participating in another trial (involving an
investigational drug and/or follow-up)



Age minimum: 18 Years
Age maximum: 84 Years
Gender: All

Health Condition(s) or Problem(s) studied

Diabetes Mellitus, Type 2

Diastolic Dysfunction

Intervention(s)

Drug: Empagliflozin

Drug: Placebo

Primary Outcome(s)

difference in E/E' ratio between 12 weeks after baseline and at baseline [Time Frame: 12 weeks]

Secondary Outcome(s)

difference in Augmentation index (AIx) [Time Frame: 12 week]

difference in Carotid-femoral pulse wave velocity [Time Frame: 1 week]

difference in Arterial stiffness index (SI) [Time Frame: 1 week]

difference in Brain natriuretic peptide (BNP) [Time Frame: 12 weeks]

difference in Arterial stiffness index (SI) [Time Frame: 12 weeks]

difference in E/E' ratio (change from baseline (V1) to 12 weeks follow-up) in the subgroup of patients with HbA1c 6.5%-6.9% [Time Frame: 12 weeks]

difference in E/E' ratio (change from baseline (V1) to 12 weeks follow-up) in the subgroup of patients with eGFR 45-59 ml/min/1.73 m² [Time Frame: 12 weeks]

difference in High sensitive C-reactive protein (hs CRP) [Time Frame: 12 weeks]

difference in High sensitive troponin I (hs TnI) [Time Frame: 1 week]

difference in Left ventricular systolic function (LVEF) [Time Frame: 1 week]

difference in Reflection index [Time Frame: 12 weeks]

difference in Carotid-femoral pulse wave velocity [Time Frame: 12 weeks]

difference in High sensitive C-reactive protein (hs CRP) [Time Frame: 1 week]

difference in Brain natriuretic peptide (BNP) [Time Frame: 1 week]

difference in Left end-diastolic volume (LEDV) [Time Frame: 12 weeks]

difference in High sensitive troponin I (hs TnI) [Time Frame: 12 weeks]

difference in Left ventricular systolic function (LVEF) [Time Frame: 12 weeks]

difference in Reflection index [Time Frame: 1 week]

difference in E/E' ratio (change from baseline (V1) to 1 week follow-up) [Time Frame: 1 week]

difference in Augmentation index (AIx) [Time Frame: 1 week]

difference in Left end-diastolic volume (LEDV) [Time Frame: 1 week]

Secondary ID(s)

2016-001264-11

UMCM-2016EPI05

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Secondary Sponsor(s)

Boehringer Ingelheim