Clinical trial NCT03753087: Effects of Empagliflozin on Exercise Capacity and Left Ventricular Diastolic Function in Patients With Heart Failure With Preserved Ejection Fraction and Type-2 Diabetes Mellitus
Official title: A Phase 4, Single-center, Randomized, Parallel Group Study to Assess Effects of Empagliflozin on Exercise Capacity and Left Ventricular Diastolic Function in Patients With Heart Failure With Preserved Ejection Fraction and Type-2 Diabetes Mellitus
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Heart Failure, Diastolic
Diabetes Mellitus, Type 2
Keywords: HF
HFpEF
DM
Empagliflozin
Jardiance
Lead sponsor: National Medical Research Center for Cardiology, Ministry of Health of Russian Federation
Sponsor class: OTHER_GOV
Collaborators: name: Ministry of Health, Russian Federation
First posted: 2018-11-26
Enrollment: 70
Sex: ALL
Minimum age (years): 45
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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 exclusion criteria may apply

Primary outcomes:
measure: Change in 6-minute walking distance (6MWD)
timeFrame: 24 weeks
Secondary outcomes:
measure: Change in left ventricular mass index (LVMI)
timeFrame: 24 weeks
measure: Change in left atrial volume index (LAVI)
timeFrame: 24 weeks
measure: Change in left atrial stiffness
timeFrame: 24 weeks
measure: Change estimated pulmonary artery systolic pressure (PASP)
timeFrame: 24 weeks
measure: Change in average e' velocity
timeFrame: 24 weeks
measure: Change in average E/e' ratio
timeFrame: 24 weeks
measure: Change in N-terminal pro b-type natriuretic peptide (NT-proBNP)
timeFrame: 24 weeks
measure: Change in Cyclic guanosine monophosphate (cGMP)
timeFrame: 24 weeks
measure: Change in Endothelin 1 (ET-1)
timeFrame: 24 weeks
measure: Change in Growth/differentiation factor 15 (GDF-15)
timeFrame: 24 weeks
measure: Change in ST2
timeFrame: 24 weeks
measure: Change in Galectin-3
timeFrame: 24 weeks
measure: Change in carboxyterminal propeptide of type I collagen (PICP)
timeFrame: 24 weeks
measure: Change in Human Pentraxin 3 (PTX3)
timeFrame: 24 weeks
measure: Change in high-sensitivity C-reactive protein (hsCRP)
timeFrame: 24 weeks
measure: Change in Interleukin-6 (IL-6)
timeFrame: 24 weeks
measure: Change of New York Heart Association (NYHA) functional classification
timeFrame: 24 weeks
measure: Change in Minnesota Living With Heart Failure Questionnaire (MLHFQ) score
timeFrame: 24 weeks
Other outcomes:
Locations:
city: Moscow
country: Russian Federation
facility: National Medical Research Center for Cardiology
Study officials:
affiliation: National Medical Research Center for Cardiology
name: Anton Borisov, MD
role: PRINCIPAL_INVESTIGATOR
References: