Empagliflozin Impact on Hemodynamics in Patients With Heart Failure

Saint Luke's Health System65 enrolled

Overview

The primary purpose of this trial is to evaluate the impact of empagliflozin, as compared with placebo, on hemodynamic parameters (pulmonary artery diastolic pressure) in patients with heart failure (reduced or preserved ejection fraction, ischemic or non-ischemic etiology) who already have a CardioMEMs device (a wireless hemodynamic monitoring system) implanted for non-study related clinical reasons.

A 12-week randomized, double-blind, placebo-controlled trial to explore the effects of once-daily empagliflozin 10 mg on hemodynamic parameters (pulmonary artery pressures) in patients with heart failure (reduced or preserved ejection fraction, ischemic or non-ischemic etiology) who already have a CardioMEMs device implanted for non-study related clinical reasons.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Enrollment

Conditions

Heart Failure

Interventions

Empagliflozin 10 mg TabDRUG

Empagliflozin 10 mg Tab

Placebo Oral TabletDRUG

Empagliflozin matching placebo

Eligibility

Sex: ALLMin age: 19 YearsMax age: 119 Years

Medical Language ↔ Plain English

Inclusion Criteria: 1. Established diagnosis of heart failure (for at least 16 weeks prior to the screening visit) with either preserved (LVEF\>40%) or reduced systolic function (LVEF≤40%), due to either ischemic or non-ischemic etiology, documented by an imaging modality (echocardiography, nuclear imaging, LV angiography, magnetic resonance imaging) within the past 24 months. 2. No major change in diuretic management for 48 hours prior to screening visit or 48 hours prior to randomization visit (major change defined by doubling of diuretic dose or addition of another diuretic medication) 3. New York Heart Association (NYHA) class II, III or IV heart failure symptoms at the screening and randomization visit 4. Presence of previously (≥ 2 weeks prior to screening visit) implanted CardioMEMs pulmonary artery pressure monitor for a clinical indication unrelated to the study. 5. Pulmonary artery diastolic pressure ≥ 12 mmHg at the time of the screening visit (last measurement available prior to the screening visit). 6. Ability to provide informed consent prior to initiating screening visit procedures Exclusion Criteria: 1. Decompensated heart failure (hospitalization for heart failure within the 2 weeks prior to screening) or between screening and randomization 2. History of type 1 diabetes 3. Major change in diuretic management during 48 hours prior to screening visit or 48 hours prior to randomization visit. (major change defined by doubling of diuretic dose or addition of another diuretic medications) 4. Significant variability in baseline pulmonary artery diastolic pressures during screening period. Defined as changes greater than +/- 6 mmHg from average pulmonary artery diastolic pressure during week 1 of the screening phase and average pulmonary artery diastolic pressure during week 2 of the screening phase for those patients with an average baseline pulmonary artery diastolic pressure during week 1 of the screening phase of \<30 mmHg. If the average baseline pulmonary artery diastolic pressure during week 1 of the screening phase is ≥30 mmHg, then ≥20% relative change in average pulmonary diastolic pressure between week 1 and week 2 of the screening phase will be used to define significant variability. 5. Initiation of hydralazine, long-acting nitrates, beta blockers, angiotensin-converting enzyme inhibitors (ACEIs) , angiotensin II receptor blockers (ARBs) or valsartan/sacubitril in the prior 4 weeks prior to screening 6. Estimated glomerular filtration rate (eGFR) \< 30 mL/min/1.73 m2 at the screening visit 7. Admission for an acute coronary syndrome (ST-elevation myocardial infarction, non-ST-elevation myocardial infarction, or unstable angina), percutaneous coronary intervention, or cardiac surgery within 30 days prior to the screening visit. 8. Implantation of cardiac resynchronization therapy (CRT) device within the previous 90 days. 9. Implantation of the CardioMEMs device within the past 2 weeks. 10. Planned cardiovascular revascularization (percutaneous intervention or surgical) or major cardiac surgery (coronary artery bypass grafting, valve replacement, ventricular assist device, cardiac transplantation, or any other surgery requiring thoracotomy), or planned implantation of cardiac resynchronization therapy (CRT) device within the 90 days after the screening visit. 11. Participation in any interventional clinical trial (with an investigational drug or device) that is not an observational registry within the 4 weeks prior to the screening visit. 12. History of hypersensitivity to empagliflozin 13. For women of child-bearing potential: Current or planned pregnancy or currently lactating 14. Life expectancy \<1 year at the screening visit 15. Patients who are volume depleted based upon physical examination at the time of the screening or randomization visit 16. Pulmonary artery diastolic pressure \< 12 mmHg at the time of the screening visit (average of last four measurements available prior to the screening visit). 17. Patients currently being treated with any SGLT-2 inhibitor (dapagliflozin, canagliflozin, empagliflozin) or having received treatment with any SGLT-2 inhibitor within the 8 weeks prior to the screening visit 18. Average supine systolic BP \<90 mmHg at the screening or randomization visit 19. Current documented history of bladder cancer 20. Active Gross Hematuria 21. Heart failure due to restrictive cardiomyopathy, active myocarditis, constrictive pericarditis, severe stenotic valve disease, and hypertrophic obstructive cardiomyopathy (HOCM). 22. History of heart transplant. 23. Patients on heart transplant list as 1a and 1b status

Locations (10)

University of Southern California

Los Angeles, California, United States

First Coast Cardiovascular Institute

Jacksonville, Florida, United States

NorthShore University Health System Research Institute

Evanston, Illinois, United States

Outcomes

Primary Outcomes

Change in Pulmonary Artery Diastolic Pressure From Baseline to End of Treatment Period (Defined as Average of Pulmonary Artery Diastolic Pressure Measurements Between Weeks 8-12) Between Empagliflozin and Placebo

Change in pulmonary artery diastolic pressure from baseline to end of treatment period (defined as average of pulmonary artery diastolic pressure measurements between weeks 8-12) between empagliflozin and placebo

Time frame: Baseline to average between Weeks 8-12

Secondary Outcomes

Change From Baseline in Pulmonary Artery Diastolic Pressure at Each Interim Timepoint (Wks 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11,12) Between Empagliflozin and Placebo.

Change from baseline in pulmonary artery diastolic pressure at each interim timepoint (wks 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11,12) between empagliflozin and placebo.

Time frame: Baseline to Weeks 1-12

Change in Pulmonary Artery Systolic Pressure From Baseline to End of Treatment Period (Week 12) Between Empagliflozin and Placebo.

Change in pulmonary artery systolic pressure from baseline to end of treatment period (week 12) between empagliflozin and placebo.

Time frame: Baseline to Week 12

Change From Baseline in Pulmonary Artery Systolic Pressure at Each Interim Time Point (Wks 1, 2, 3, 4, 5, 6, 7, 8, 9,10,11,12) Between Empagliflozin and Placebo.

Change from baseline in pulmonary artery systolic pressure at each interim time point (wks 1, 2, 3, 4, 5, 6, 7, 8, 9,10,11,12) between empagliflozin and placebo.

Time frame: Baseline to Weeks 1-12

Change in Mean Pulmonary Artery Pressure From Baseline to End of Treatment Period (Week 12) Between Empagliflozin and Placebo.

Change in mean pulmonary artery pressure from baseline to end of treatment period (week 12) between empagliflozin and placebo.

Data from ClinicalTrials.gov

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CentraCare Heart and Vascular Center

Saint Cloud, Minnesota, United States

St. Francis Hospital

Roslyn, New York, United States

Ohio State University

Columbus, Ohio, United States

Sanford Research

Sioux Falls, South Dakota, United States

Austin Heart Clinical Research

Austin, Texas, United States

Baylor College of Medicine

Houston, Texas, United States

Sentara Cardiovascular Research Institute

Norfolk, Virginia, United States

Time frame: Baseline to Week 12

Change From Baseline in Mean Pulmonary Artery Pressure at Each Interim Time Point (Weeks 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 and 12) Between Empagliflozin and Placebo.

Change from baseline in mean pulmonary artery pressure at each interim time point (weeks 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 and 12) between empagliflozin and placebo.

Time frame: Baseline to Weeks 1-12

Change in Heart Failure Related Quality of Life, Using the Kansas City Cardiomyopathy Questionnaire Overall Summary Score (KCCQ-OS) From Baseline to Follow-up (Defines as Average of Measurements at 6 and 12 Weeks) Between Empagliflozin and Placebo.

The Kansas City Cardiomyopathy Questionnaire (KCCQ) is a disease-specific health status instrument composed of 23 items that quantifies the domains of physical limitations, symptoms, self-efficacy, social limitation and quality of life from heart failure. Scores range from 0-100, in which higher scores reflect better health status. For the Kansas City Cardiomyopathy Questionnaire Overall Summary Score KCCQ-OS, a small but clinically meaningful change is considered to be ≥ 5 points.