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

Diabetes Mellitus, Type 2 Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03753087
• Other study ID #: 2018-9-25
• Status: Completed
• Phase: Phase 4
• Start date: January 16, 2019
• Est. completion date: January 10, 2022

Study information

• Verified date: January 2022
• Source: National Medical Research Center for Cardiology, Ministry of Health of Russian Federation
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 70
• Est. completion date: January 10, 2022
• Est. primary completion date: December 16, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 45 Years to 80 Years

Eligibility

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

Related Conditions & MeSH terms

• Diabetes Mellitus
• Diabetes Mellitus, Type 2
• Heart Failure
• Heart Failure, Diastolic

Intervention

Drug:
• Empagliflozin
10 mg tablet

Other:
• Standard care
Standard care with no SGLT-2 inhibitors

Locations

Country	Name	City	State
Russian Federation	National Medical Research Center for Cardiology	Moscow

Sponsors (2)

Lead Sponsor	Collaborator
National Medical Research Center for Cardiology, Ministry of Health of Russian Federation	Ministry of Health of the Russian Federation

Country where clinical trial is conducted

Russian Federation, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in 6-minute walking distance (6MWD)	Difference in distance walked during 6-minute walking test (6MWT) between 24 weeks after baseline and at baseline	24 weeks
Secondary	Change in left ventricular mass index (LVMI)	Difference in LVMI assessed by echocardiography between 24 weeks after baseline and at baseline	24 weeks
Secondary	Change in left atrial volume index (LAVI)	Difference in LAVI assessed by echocardiography between 24 weeks after baseline and at baseline	24 weeks
Secondary	Change in left atrial stiffness	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	24 weeks
Secondary	Change estimated pulmonary artery systolic pressure (PASP)	Difference in PASP assessed by echocardiography both at rest and during diastolic stress test (DST) between 24 weeks after baseline and at baseline	24 weeks
Secondary	Change in average e' velocity	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	24 weeks
Secondary	Change in average E/e' ratio	Difference in average E/e' ratio assessed by echocardiography both at rest and during diastolic stress between 24 weeks after baseline and at baseline	24 weeks
Secondary	Change in N-terminal pro b-type natriuretic peptide (NT-proBNP)	Difference in NT-proBNP plasma levels between 24 weeks after baseline and at baseline	24 weeks
Secondary	Change in Cyclic guanosine monophosphate (cGMP)	Difference in cGMP plasma levels between 24 weeks after baseline and at baseline	24 weeks
Secondary	Change in Endothelin 1 (ET-1)	Difference in ET-1 plasma levels between 24 weeks after baseline and at baseline	24 weeks
Secondary	Change in Growth/differentiation factor 15 (GDF-15)	Difference in GDF-15 plasma levels between 24 weeks after baseline and at baseline	24 weeks
Secondary	Change in ST2	Difference in ST2 plasma levels between 24 weeks after baseline and at baseline	24 weeks
Secondary	Change in Galectin-3	Difference in Galectin-3 plasma levels between 24 weeks after baseline and at baseline	24 weeks
Secondary	Change in carboxyterminal propeptide of type I collagen (PICP)	Difference in PICP plasma levels between 24 weeks after baseline and at baseline	24 weeks
Secondary	Change in Human Pentraxin 3 (PTX3)	Difference in PTX3 plasma levels between 24 weeks after baseline and at baseline	24 weeks
Secondary	Change in high-sensitivity C-reactive protein (hsCRP)	Difference in hsCRP plasma levels between 24 weeks after baseline and at baseline	24 weeks
Secondary	Change in Interleukin-6 (IL-6)	Difference in IL-6 plasma levels between 24 weeks after baseline and at baseline	24 weeks
Secondary	Change of New York Heart Association (NYHA) functional classification	Difference in NYHA class between 24 weeks after baseline and at baseline	24 weeks
Secondary	Change in Minnesota Living With Heart Failure Questionnaire (MLHFQ) score	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).	24 weeks