Empagliflozin Impact on Hemodynamics in Patients With Heart Failure (EMBRACE-HF)

Saint Luke's Health System

Status and phase: Completed; Phase 4

Conditions: Heart Failure

Treatments: Drug: Empagliflozin 10 mg Tab; Drug: Placebo Oral Tablet

Study type: Interventional

Funder types: Other

Identifiers

NCT03030222

1245.129

Details and patient eligibility

About

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.

Full description

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.

Enrollment: 65 patients

Sex: All

Ages: 19 to 119 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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65 participants in 2 patient groups, including a placebo group

Empagliflozin

Active Comparator group

Description:

Empagliflozin 10 mg tab, once daily, for 12 weeks

Treatment:

Drug: Empagliflozin 10 mg Tab

Placebo

Placebo Comparator group

Description:

Empagliflozin matching placebo oral tablet, once daily for 12 weeks

Treatment:

Drug: Placebo Oral Tablet