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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

Primary Purpose

Heart Failure, Diastolic, Diabetes Mellitus, Type 2

Status
Completed
Phase
Phase 4
Locations
Russian Federation
Study Type
Interventional
Intervention
Empagliflozin
Standard care
Sponsored by
National Medical Research Center for Cardiology, Ministry of Health of Russian Federation
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Heart Failure, Diastolic focused on measuring HF, HFpEF, DM, Empagliflozin, Jardiance

Eligibility Criteria

45 Years - 80 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • National Medical Research Center for Cardiology

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

Empagliflozin

Control

Arm Description

Patients will receive standard care for Heart Failure and Diabetes Mellitus + Empagliflozin 10mg once daily

Patients will receive standard care for Heart Failure and Diabetes Mellitus with no SGLT-2 inhibitors

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

Change in left ventricular mass index (LVMI)
Difference in LVMI assessed by echocardiography between 24 weeks after baseline and at baseline
Change in left atrial volume index (LAVI)
Difference in LAVI assessed by echocardiography between 24 weeks after baseline and at baseline
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
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
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
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
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
Change in Cyclic guanosine monophosphate (cGMP)
Difference in cGMP plasma levels between 24 weeks after baseline and at baseline
Change in Endothelin 1 (ET-1)
Difference in ET-1 plasma levels between 24 weeks after baseline and at baseline
Change in Growth/differentiation factor 15 (GDF-15)
Difference in GDF-15 plasma levels between 24 weeks after baseline and at baseline
Change in ST2
Difference in ST2 plasma levels between 24 weeks after baseline and at baseline
Change in Galectin-3
Difference in Galectin-3 plasma levels between 24 weeks after baseline and at baseline
Change in carboxyterminal propeptide of type I collagen (PICP)
Difference in PICP plasma levels between 24 weeks after baseline and at baseline
Change in Human Pentraxin 3 (PTX3)
Difference in PTX3 plasma levels between 24 weeks after baseline and at baseline
Change in high-sensitivity C-reactive protein (hsCRP)
Difference in hsCRP plasma levels between 24 weeks after baseline and at baseline
Change in Interleukin-6 (IL-6)
Difference in IL-6 plasma levels between 24 weeks after baseline and at baseline
Change of New York Heart Association (NYHA) functional classification
Difference in NYHA class between 24 weeks after baseline and at baseline
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).

Full Information

First Posted
November 21, 2018
Last Updated
January 10, 2022
Sponsor
National Medical Research Center for Cardiology, Ministry of Health of Russian Federation
Collaborators
Ministry of Health of the Russian Federation
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1. Study Identification

Unique Protocol Identification Number
NCT03753087
Brief Title
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

2. Study Status

Record Verification Date
January 2022
Overall Recruitment Status
Completed
Study Start Date
January 16, 2019 (Actual)
Primary Completion Date
December 16, 2021 (Actual)
Study Completion Date
January 10, 2022 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
National Medical Research Center for Cardiology, Ministry of Health of Russian Federation
Collaborators
Ministry of Health of the Russian Federation

4. Oversight

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

5. 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Heart Failure, Diastolic, Diabetes Mellitus, Type 2
Keywords
HF, HFpEF, DM, Empagliflozin, Jardiance

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
70 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Empagliflozin
Arm Type
Experimental
Arm Description
Patients will receive standard care for Heart Failure and Diabetes Mellitus + Empagliflozin 10mg once daily
Arm Title
Control
Arm Type
Active Comparator
Arm Description
Patients will receive standard care for Heart Failure and Diabetes Mellitus with no SGLT-2 inhibitors
Intervention Type
Drug
Intervention Name(s)
Empagliflozin
Intervention Description
10 mg tablet
Intervention Type
Other
Intervention Name(s)
Standard care
Intervention Description
Standard care with no SGLT-2 inhibitors
Primary Outcome Measure Information:
Title
Change in 6-minute walking distance (6MWD)
Description
Difference in distance walked during 6-minute walking test (6MWT) between 24 weeks after baseline and at baseline
Time Frame
24 weeks
Secondary Outcome Measure Information:
Title
Change in left ventricular mass index (LVMI)
Description
Difference in LVMI assessed by echocardiography between 24 weeks after baseline and at baseline
Time Frame
24 weeks
Title
Change in left atrial volume index (LAVI)
Description
Difference in LAVI assessed by echocardiography between 24 weeks after baseline and at baseline
Time Frame
24 weeks
Title
Change in left atrial stiffness
Description
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
Time Frame
24 weeks
Title
Change estimated pulmonary artery systolic pressure (PASP)
Description
Difference in PASP assessed by echocardiography both at rest and during diastolic stress test (DST) between 24 weeks after baseline and at baseline
Time Frame
24 weeks
Title
Change in average e' velocity
Description
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
Time Frame
24 weeks
Title
Change in average E/e' ratio
Description
Difference in average E/e' ratio assessed by echocardiography both at rest and during diastolic stress between 24 weeks after baseline and at baseline
Time Frame
24 weeks
Title
Change in N-terminal pro b-type natriuretic peptide (NT-proBNP)
Description
Difference in NT-proBNP plasma levels between 24 weeks after baseline and at baseline
Time Frame
24 weeks
Title
Change in Cyclic guanosine monophosphate (cGMP)
Description
Difference in cGMP plasma levels between 24 weeks after baseline and at baseline
Time Frame
24 weeks
Title
Change in Endothelin 1 (ET-1)
Description
Difference in ET-1 plasma levels between 24 weeks after baseline and at baseline
Time Frame
24 weeks
Title
Change in Growth/differentiation factor 15 (GDF-15)
Description
Difference in GDF-15 plasma levels between 24 weeks after baseline and at baseline
Time Frame
24 weeks
Title
Change in ST2
Description
Difference in ST2 plasma levels between 24 weeks after baseline and at baseline
Time Frame
24 weeks
Title
Change in Galectin-3
Description
Difference in Galectin-3 plasma levels between 24 weeks after baseline and at baseline
Time Frame
24 weeks
Title
Change in carboxyterminal propeptide of type I collagen (PICP)
Description
Difference in PICP plasma levels between 24 weeks after baseline and at baseline
Time Frame
24 weeks
Title
Change in Human Pentraxin 3 (PTX3)
Description
Difference in PTX3 plasma levels between 24 weeks after baseline and at baseline
Time Frame
24 weeks
Title
Change in high-sensitivity C-reactive protein (hsCRP)
Description
Difference in hsCRP plasma levels between 24 weeks after baseline and at baseline
Time Frame
24 weeks
Title
Change in Interleukin-6 (IL-6)
Description
Difference in IL-6 plasma levels between 24 weeks after baseline and at baseline
Time Frame
24 weeks
Title
Change of New York Heart Association (NYHA) functional classification
Description
Difference in NYHA class between 24 weeks after baseline and at baseline
Time Frame
24 weeks
Title
Change in Minnesota Living With Heart Failure Questionnaire (MLHFQ) score
Description
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).
Time Frame
24 weeks

10. Eligibility

Sex
All
Minimum Age & Unit of Time
45 Years
Maximum Age & Unit of Time
80 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Males and females aged 45 to 80 years at screening Diagnosis of type-2 diabetes mellitus with stable glucose-lowering background therapy for at least 12 weeks HbA1c ≥ 6,5% and ≤ 10% at screening 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] Signed and dated informed consent Exclusion Criteria: Pretreatment with empagliflozin or other SGLT-2 inhibitor within the last 2 months Type-1 diabetes mellitus NYHA classification IV or acute decompensated heart failure at screening Impaired renal function, defined as eGFR <30 ml/min/1.73 m² of body-surface-area (CKD-EPI) Systolic blood pressure > 180 mmHg or < 90 mmHg Permanent atrial flutter or atrial fibrillation Other conditions that may be responsible for impaired diastolic function such as hypertrophic/restrictive cardiomyopathy, constrictive pericarditis and etc. Anemia (Hb < 100 g/l) Myocardial infarction, coronary artery bypass graft surgery within the last 3 months Stroke or TIA within the last 3 months Indications of liver disease Acute genital infection or urinary tract infection Pregnancy Additional exclusion criteria may apply
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Anton Borisov, MD
Organizational Affiliation
National Medical Research Center for Cardiology
Official's Role
Principal Investigator
Facility Information:
Facility Name
National Medical Research Center for Cardiology
City
Moscow
ZIP/Postal Code
121552
Country
Russian Federation

12. IPD Sharing Statement

Learn more about this trial

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

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