Empagliflozin Impact on Hemodynamics in Patients With Heart Failure
Condition: Heart Failure
MeSH terms: Heart Failure
Intervention: Empagliflozin 10 mg Tab; Placebo Oral Tablet
Intervention description: Empagliflozin 10 mg Tab; Empagliflozin matching placebo
Intervention MeSH terms: Empagliflozin
Phase: Phase 4
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 65.0
Sex: All
Minimum age: 19 Years
Maximum age: 119 Years
Healthy volunteers: No
Keywords: heart failure; empagliflozin; Sodium-glucose Cotransporter-2 (SGLT2) Inhibitors

Summary:

      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.
    

Eligibility criteria:

        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