Diabetes Mellitus, Type 2, Heart Failure, Diastolic
Conditions
Keywords
HF, HFpEF, DM, Empagliflozin, Jardiance
Brief summary
Patients enrolled into the study will be randomly allocated either to Empagliflozin group or control group. In the Empagliflozin group patients will be receiving standard care + Empagliflozin 10 mg o.d., in the control group patients will be receiving standard care without sodium glucose contransporter 2 (SGLT2) inhibitors.
Interventions
DRUGEmpagliflozin
10 mg tablet
OTHERStandard care
Standard care with no SGLT-2 inhibitors
Sponsors
Ministry of Health, Russian Federation
National Medical Research Center for Cardiology, Ministry of Health of Russian Federation
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
45 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
1. Males and females aged 45 to 80 years at screening 2. Diagnosis of type-2 diabetes mellitus with stable glucose-lowering background therapy for at least 12 weeks 3. HbA1c ≥ 6,5% and ≤ 10% at screening 4. Diagnosis of HFpEF which includes: * Symptoms ± signs (as defined in 2016 European Society of Cardiology guidelines for the diagnosis and treatment of acute and chronic heart failure) * Ejection fraction ≥ 50% (by Simpson) * Increased LV filling pressures at rest or during exercise determined by echocardiography (LV diastolic dysfunction grade II/III and/or positive diastolic stress test) \[according to American Society of Echocardiography and European Association of Cardiovascular Imaging (ASE/EACVI) Recommendations for the Evaluation of Left Ventricular Diastolic Function by Echocardiography, 2016\] 5. Signed and dated informed consent
Exclusion criteria
1. Pretreatment with empagliflozin or other SGLT-2 inhibitor within the last 2 months 2. Type-1 diabetes mellitus 3. NYHA classification IV or acute decompensated heart failure at screening 4. Impaired renal function, defined as eGFR \<30 ml/min/1.73 m² of body-surface-area (CKD-EPI) 5. Systolic blood pressure \> 180 mmHg or \< 90 mmHg 6. Permanent atrial flutter or atrial fibrillation 7. Other conditions that may be responsible for impaired diastolic function such as hypertrophic/restrictive cardiomyopathy, constrictive pericarditis and etc. 8. Anemia (Hb \< 100 g/l) 9. Myocardial infarction, coronary artery bypass graft surgery within the last 3 months 10. Stroke or TIA within the last 3 months 11. Indications of liver disease 12. Acute genital infection or urinary tract infection 13. Pregnancy 14. Additional
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in 6-minute walking distance (6MWD) | 24 weeks | Difference in distance walked during 6-minute walking test (6MWT) between 24 weeks after baseline and at baseline |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in left atrial volume index (LAVI) | 24 weeks | Difference in LAVI assessed by echocardiography between 24 weeks after baseline and at baseline |
| Change in left atrial stiffness | 24 weeks | Difference in left atrial stiffness assessed as a ratio of mitral E/e' ratio to left atrial strain s between 24 weeks after baseline and at baseline |
| Change estimated pulmonary artery systolic pressure (PASP) | 24 weeks | Difference in PASP assessed by echocardiography both at rest and during diastolic stress test (DST) between 24 weeks after baseline and at baseline |
| Change in average e' velocity | 24 weeks | Difference in average e' velocity assessed by echocardiography both at rest and during diastolic stress test (DST) between 24 weeks after baseline and at baseline |
| Change in average E/e' ratio | 24 weeks | Difference in average E/e' ratio assessed by echocardiography both at rest and during diastolic stress between 24 weeks after baseline and at baseline |
| Change in N-terminal pro b-type natriuretic peptide (NT-proBNP) | 24 weeks | Difference in NT-proBNP plasma levels between 24 weeks after baseline and at baseline |
| Change in Cyclic guanosine monophosphate (cGMP) | 24 weeks | Difference in cGMP plasma levels between 24 weeks after baseline and at baseline |
| Change in Endothelin 1 (ET-1) | 24 weeks | Difference in ET-1 plasma levels between 24 weeks after baseline and at baseline |
| Change in left ventricular mass index (LVMI) | 24 weeks | Difference in LVMI assessed by echocardiography between 24 weeks after baseline and at baseline |
| Change in ST2 | 24 weeks | Difference in ST2 plasma levels between 24 weeks after baseline and at baseline |
| Change in Galectin-3 | 24 weeks | Difference in Galectin-3 plasma levels between 24 weeks after baseline and at baseline |
| Change in carboxyterminal propeptide of type I collagen (PICP) | 24 weeks | Difference in PICP plasma levels between 24 weeks after baseline and at baseline |
| Change in Human Pentraxin 3 (PTX3) | 24 weeks | Difference in PTX3 plasma levels between 24 weeks after baseline and at baseline |
| Change in high-sensitivity C-reactive protein (hsCRP) | 24 weeks | Difference in hsCRP plasma levels between 24 weeks after baseline and at baseline |
| Change in Interleukin-6 (IL-6) | 24 weeks | Difference in IL-6 plasma levels between 24 weeks after baseline and at baseline |
| Change of New York Heart Association (NYHA) functional classification | 24 weeks | Difference in NYHA class between 24 weeks after baseline and at baseline |
| Change in Minnesota Living With Heart Failure Questionnaire (MLHFQ) score | 24 weeks | Difference in MLHFQ score between 24 weeks after baseline and at baseline. The questionnaire is comprised of 21 important physical, emotional and socioeconomic ways heart failure can adversely affect a patient's life. After receiving brief standardized instructions, the patient marks a 0 (zero) to 5 scale to indicate how much each itemized adverse of heart failure has prevented the patient from living as he or she wanted to live during the past 4 weeks. The questionnaire is simply scored by summation of all 21 responses. Score ranges from 0 (best quality of life) to 105 (worst quality of life). |
| Change in Growth/differentiation factor 15 (GDF-15) | 24 weeks | Difference in GDF-15 plasma levels between 24 weeks after baseline and at baseline |
Countries
Russia
Outcome results
None listed