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

• Status: Completed
• Trial end date: 2020-08-31
• Target enrollment: 0
• Participant gender: All

Summary

The purpose of the EmDia trial is to compare the effects of empagliflozin with placebo in addition to standard diabetic treatment or dietetic treatment on cardiac diastolic function in patients with type 2 Diabetes mellitus.

• Phase: Phase 4
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Johannes Gutenberg University Mainz
• Collaborator: Boehringer Ingelheim
• Treatments: Empagliflozin

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)