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

• Sponsor: National Medical Research Center for Cardiology, Ministry of Health of Russian Federation (Other)
• Overall Status: Completed
• CT.gov ID: NCT03753087
• Collaborator: Ministry of Health of the Russian Federation (Other)
• Enrollment: 70
• Location: 1
• Arms: 2
• Actual Duration (Months): 35.8
• Patients Per Site Per Month: 2

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Heart Failure, Diastolic; Diabetes Mellitus, Type 2	Drug: Empagliflozin; Other: Standard care	Phase 4

Study Design

• Study Type: Interventional
• Actual Enrollment: 70 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• 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
• Actual Study Start Date: Jan 16, 2019
• Actual Primary Completion Date: Dec 16, 2021
• Actual Study Completion Date: Jan 10, 2022

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Empagliflozin Patients will receive standard care for Heart Failure and Diabetes Mellitus + Empagliflozin 10mg once daily	Drug: Empagliflozin; 10 mg tablet
Active Comparator: Control Patients will receive standard care for Heart Failure and Diabetes Mellitus with no SGLT-2 inhibitors	Other: Standard care; Standard care with no SGLT-2 inhibitors

Outcome Measures

Primary Outcome Measures

1. 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

1. Change in left ventricular mass index (LVMI) [24 weeks]

   Difference in LVMI assessed by echocardiography between 24 weeks after baseline and at baseline

2. Change in left atrial volume index (LAVI) [24 weeks]

   Difference in LAVI assessed by echocardiography between 24 weeks after baseline and at baseline

3. 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

4. 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

5. 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

6. 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

7. 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

8. Change in Cyclic guanosine monophosphate (cGMP) [24 weeks]

   Difference in cGMP plasma levels between 24 weeks after baseline and at baseline

9. Change in Endothelin 1 (ET-1) [24 weeks]

   Difference in ET-1 plasma levels between 24 weeks after baseline and at baseline

10. Change in Growth/differentiation factor 15 (GDF-15) [24 weeks]

    Difference in GDF-15 plasma levels between 24 weeks after baseline and at baseline

11. Change in ST2 [24 weeks]

    Difference in ST2 plasma levels between 24 weeks after baseline and at baseline

12. Change in Galectin-3 [24 weeks]

    Difference in Galectin-3 plasma levels between 24 weeks after baseline and at baseline

13. Change in carboxyterminal propeptide of type I collagen (PICP) [24 weeks]

    Difference in PICP plasma levels between 24 weeks after baseline and at baseline

14. Change in Human Pentraxin 3 (PTX3) [24 weeks]

    Difference in PTX3 plasma levels between 24 weeks after baseline and at baseline

15. Change in high-sensitivity C-reactive protein (hsCRP) [24 weeks]

    Difference in hsCRP plasma levels between 24 weeks after baseline and at baseline

16. Change in Interleukin-6 (IL-6) [24 weeks]

    Difference in IL-6 plasma levels between 24 weeks after baseline and at baseline

17. Change of New York Heart Association (NYHA) functional classification [24 weeks]

    Difference in NYHA class between 24 weeks after baseline and at baseline

18. 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).

Eligibility Criteria

Criteria

• Ages Eligible for Study: 45 Years to 80 Years
• Sexes Eligible for Study: All
• Accepts 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]

1. 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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	National Medical Research Center for Cardiology	Moscow		Russian Federation	121552

Sponsors and Collaborators

• National Medical Research Center for Cardiology, Ministry of Health of Russian Federation
• Ministry of Health of the Russian Federation

Investigators

• Principal Investigator: Anton Borisov, MD, National Medical Research Center for Cardiology

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Anton Borisov, Principal Investigator, MD, National Medical Research Center for Cardiology, Ministry of Health of Russian Federation
• ClinicalTrials.gov Identifier: NCT03753087
• Other Study ID Numbers: 2018-9-25
• First Posted: Nov 26, 2018
• Last Update Posted: Jan 11, 2022
• Last Verified: Jan 1, 2022

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: No
• Keywords provided by Anton Borisov, Principal Investigator, MD, National Medical Research Center for Cardiology, Ministry of Health of Russian Federation: HF; HFpEF; DM; Empagliflozin; Jardiance
• Additional relevant MeSH terms: Heart Failure; Heart Failure, Diastolic; Diabetes Mellitus; Diabetes Mellitus, Type 2; Empagliflozin

Study Results

No Results Posted as of Jan 11, 2022