Empagliflozin Impact on Hemodynamics in Patients With Heart Failure

NCT ID: NCT03030222

Last Updated: 2021-12-09

Study Results

Results available

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE4

Total Enrollment

65 participants

Study Classification

INTERVENTIONAL

Study Start Date

2017-07-05

Study Completion Date

2020-03-10

Brief Summary

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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.

Detailed Description

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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.

Conditions

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Heart Failure

Keywords

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heart failure empagliflozin Sodium-glucose Cotransporter-2 (SGLT2) Inhibitors

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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Empagliflozin

Empagliflozin 10 mg tab, once daily, for 12 weeks

Group Type ACTIVE_COMPARATOR

Empagliflozin 10 mg Tab

Intervention Type DRUG

Empagliflozin 10 mg Tab

Placebo

Empagliflozin matching placebo oral tablet, once daily for 12 weeks

Group Type PLACEBO_COMPARATOR

Placebo Oral Tablet

Intervention Type DRUG

Empagliflozin matching placebo

Interventions

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Empagliflozin 10 mg Tab

Empagliflozin 10 mg Tab

Intervention Type DRUG

Placebo Oral Tablet

Empagliflozin matching placebo

Intervention Type DRUG

Other Intervention Names

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Jardiance Placebo

Eligibility Criteria

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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
Minimum Eligible Age

19 Years

Maximum Eligible Age

119 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Saint Luke's Health System

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Mikhail Kosiborod, MD

Role: STUDY_CHAIR

Saint Luke's Mid America Heart Institute

Locations

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University of Southern California

Los Angeles, California, United States

Site Status

First Coast Cardiovascular Institute

Jacksonville, Florida, United States

Site Status

NorthShore University Health System Research Institute

Evanston, Illinois, United States

Site Status

CentraCare Heart and Vascular Center

Saint Cloud, Minnesota, United States

Site Status

St. Francis Hospital

Roslyn, New York, United States

Site Status

Ohio State University

Columbus, Ohio, United States

Site Status

Sanford Research

Sioux Falls, South Dakota, United States

Site Status

Austin Heart Clinical Research

Austin, Texas, United States

Site Status

Baylor College of Medicine

Houston, Texas, United States

Site Status

Sentara Cardiovascular Research Institute

Norfolk, Virginia, United States

Site Status

Countries

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United States

References

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Nassif ME, Qintar M, Windsor SL, Jermyn R, Shavelle DM, Tang F, Lamba S, Bhatt K, Brush J, Civitello A, Gordon R, Jonsson O, Lampert B, Pelzel J, Kosiborod MN. Empagliflozin Effects on Pulmonary Artery Pressure in Patients With Heart Failure: Results From the EMBRACE-HF Trial. Circulation. 2021 Apr 27;143(17):1673-1686. doi: 10.1161/CIRCULATIONAHA.120.052503. Epub 2021 Feb 8.

Reference Type RESULT
PMID: 33550815 (View on PubMed)

Nassif ME, Spertus JA, Tang F, Windsor SL, Jones P, Thomas M, Khariton Y, Brush J, Gordon RA, Jermyn R, Jonsson O, Lamba S, Shavelle DM, Kosiborod MN. Association Between Change in Ambulatory Hemodynamic Pressures and Symptoms of Heart Failure. Circ Heart Fail. 2021 Nov;14(11):e008446. doi: 10.1161/CIRCHEARTFAILURE.121.008446. Epub 2021 Oct 26. No abstract available.

Reference Type DERIVED
PMID: 34696602 (View on PubMed)

Nassif ME, Kosiborod M. Effects of sodium glucose cotransporter type 2 inhibitors on heart failure. Diabetes Obes Metab. 2019 Apr;21 Suppl 2:19-23. doi: 10.1111/dom.13678.

Reference Type DERIVED
PMID: 31081589 (View on PubMed)

Provided Documents

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Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Related Links

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Other Identifiers

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1245.129

Identifier Type: -

Identifier Source: org_study_id