Empagliflozin Impact on Hemodynamics in Patients With Heart Failure

NCT03030222 | Completed Phase 4 Results DMC FDA Drug

• 1 other identifier: 1245.129
• Study Type: interventional
• Target: 65
• Locations: 1 country
• Sites: 10

Brief 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.

Conditions

Heart Failure

Keywords

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

Outcome Measures

Primary Outcomes (1)

• 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

  Baseline to average between Weeks 8-12

Secondary Outcomes (15)

• 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.

  Baseline to Weeks 1-12

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

  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.

  Baseline to Weeks 1-12

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

  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.

  Baseline to Weeks 1-12

Study Arms (2)

Empagliflozin

ACTIVE COMPARATOR

Empagliflozin 10 mg tab, once daily, for 12 weeks

Drug: Empagliflozin 10 mg Tab

Placebo

PLACEBO COMPARATOR

Empagliflozin matching placebo oral tablet, once daily for 12 weeks

Drug: Placebo Oral Tablet

Interventions

Empagliflozin 10 mg Tab DRUG

Empagliflozin 10 mg Tab

Also known as: Jardiance

Empagliflozin

Placebo Oral Tablet DRUG

Empagliflozin matching placebo

Also known as: Placebo

Placebo

Eligibility Criteria

• Age: 19 Years - 119 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• 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)
• New York Heart Association (NYHA) class II, III or IV heart failure symptoms at the screening and randomization visit
• Presence of previously (≥ 2 weeks prior to screening visit) implanted CardioMEMs pulmonary artery pressure monitor for a clinical indication unrelated to the study.
• Pulmonary artery diastolic pressure ≥ 12 mmHg at the time of the screening visit (last measurement available prior to the screening visit).
• Ability to provide informed consent prior to initiating screening visit procedures

You may not qualify if:

• Decompensated heart failure (hospitalization for heart failure within the 2 weeks prior to screening) or between screening and randomization
• History of type 1 diabetes
• 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)
• 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.
• 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
• Estimated glomerular filtration rate (eGFR) \< 30 mL/min/1.73 m2 at the screening visit
• 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.
• Implantation of cardiac resynchronization therapy (CRT) device within the previous 90 days.
• Implantation of the CardioMEMs device within the past 2 weeks.
• 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.
• 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.
• History of hypersensitivity to empagliflozin
• For women of child-bearing potential: Current or planned pregnancy or currently lactating
• Life expectancy \<1 year at the screening visit
• Patients who are volume depleted based upon physical examination at the time of the screening or randomization visit

Sponsors & Collaborators

• Saint Luke's Health System: lead

Study Sites (10)

University of Southern California

Los Angeles, California, 90033, United States

Location

First Coast Cardiovascular Institute

Jacksonville, Florida, 32256, United States

Location

NorthShore University Health System Research Institute

Evanston, Illinois, 60201, United States

Location

CentraCare Heart and Vascular Center

Saint Cloud, Minnesota, 56303, United States

Location

St. Francis Hospital

Roslyn, New York, 11576, United States

Location

Ohio State University

Columbus, Ohio, 43210, United States

Location

Sanford Research

Sioux Falls, South Dakota, 57104, United States

Location

Austin Heart Clinical Research

Austin, Texas, 78756, United States

Location

Baylor College of Medicine

Houston, Texas, 77030, United States

Location

Sentara Cardiovascular Research Institute

Norfolk, Virginia, 23507, United States

Location

Related Publications (3)

• 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.

  PMID: 33550815 RESULT

• 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.

  PMID: 34696602 DERIVED

• 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.

  PMID: 31081589 DERIVED

Related Links

• Empagliflozin information

MeSH Terms

Conditions

Heart Failure

Interventions

empagliflozin

Condition Hierarchy (Ancestors)

Heart Diseases; Cardiovascular Diseases

Results Point of Contact

• Title: Study Manager
• Organization: Saint Luke's Hospital of Kansas City

EMBRACE-HF@saint-lukes.org

816-932-9858

Study Officials

• Mikhail Kosiborod, MD

  Saint Luke's Mid America Heart Institute

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 20, 2017
• First Posted: January 24, 2017
• Study Start: July 5, 2017
• Primary Completion: March 10, 2020
• Study Completion: March 10, 2020
• Last Updated: December 9, 2021
• Results First Posted: December 9, 2021

Record last verified: 2021-11

Data Sharing

• IPD Sharing: Will not share

Locations

US (10)