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

Phase 4

Completed

• Conditions: Heart Failure, Diastolic; Diabetes Mellitus, Type 2
• Interventions: Other: Standard care; Drug: Empagliflozin

• Registration Number: NCT03753087
• Lead Sponsor: National Medical Research Center for Cardiology, Ministry of Health of Russian Federation

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2018-11-21
• Study First Submitted QC: 2018-11-23
• Study First Posted: 2018-11-26
• Study Start: 2019-01-16
• Primary Completion: 2021-12-16
• Status Verified: 2022-01
• Study Completion: 2022-01-10
• Last Update Submitted: 2022-01-10
• Last Update Posted: 2022-01-11

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 70

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Control	Standard care	Patients will receive standard care for Heart Failure and Diabetes Mellitus with no SGLT-2 inhibitors
Empagliflozin	Empagliflozin	Patients will receive standard care for Heart Failure and Diabetes Mellitus + Empagliflozin 10mg once daily

Primary Outcome Measures

Name	Time	Method
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 Outcome Measures

Name	Time	Method
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 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 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 Endothelin 1 (ET-1)	24 weeks	Difference in ET-1 plasma levels 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 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 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 left ventricular mass index (LVMI)	24 weeks	Difference in LVMI assessed by echocardiography between 24 weeks after baseline and at baseline
Change in left atrial volume index (LAVI)	24 weeks	Difference in LAVI assessed by echocardiography 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 Interleukin-6 (IL-6)	24 weeks	Difference in IL-6 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 Growth/differentiation factor 15 (GDF-15)	24 weeks	Difference in GDF-15 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 Galectin-3	24 weeks	Difference in Galectin-3 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

Trial Locations

Locations (1)

National Medical Research Center for Cardiology; 🇷🇺 Moscow, Russian Federation