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Empagliflozin in Heart Failure Patients With Reduced Ejection Fraction (Empire HF)

Primary Purpose

Heart Failure With Reduced Ejection Fraction

Status
Completed
Phase
Phase 2
Locations
Denmark
Study Type
Interventional
Intervention
Empagliflozin 10 MG
Placebo
Sponsored by
Morten Schou
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Heart Failure With Reduced Ejection Fraction

Eligibility Criteria

18 Years - 85 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Optimal Heart Failure Therapy in accordance with European and National Guidelines
  • LVEF ≤ 0.40
  • eGFR > 30 ml/min/1.73 m2
  • BMI < 45 kg/m2
  • NYHA class I-III
  • Age > 18 years
  • If T2D - optimal treatment in accordance with European and National Guidelines
  • If T2D - stable doses of antiglycemic treatment for 30 days
  • If T2D - HbA1C 6.5-10%

Exclusion Criteria:

  • CRT-D/-P implanted < 90 days
  • Uncorrected severe valvular disease
  • Non-compliance
  • Use of metalozone
  • NYHA IV
  • Age > 85 years
  • Dementia
  • Admission for HF < 30 days
  • Admission for hypoglycemia < 12 month
  • Known sustained VT
  • Symptomatic hypotension and systolic BP < 95 mmHg
  • Unable to perform an exercise test
  • Immobilization
  • Pregnancy
  • Participation in other medical trials
  • Previous intolerance of Empagliflozin or excipients

Sites / Locations

  • Herlev and Gentofte University Hospital
  • Odense University Hospital

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Placebo Comparator

Arm Label

Empagliflozin 10 mg

Placebo

Arm Description

Outcomes

Primary Outcome Measures

Between-group difference in the change of plasma concentrations of NT-proBNP

Secondary Outcome Measures

Between-group difference in the change in daily activity level measured by patient-worn accelerometers as change in the amount of daily average accelerometer units
Between-group difference in the change in body composition assessed by DXA scan
Between-group difference in the change of estimated extracellular volume assessed by Cr-51 EDTA clearance
Between-group difference in the change of estimated plasma volume assessed by hematocrit and hemoglobin
Between-group difference in the change of glucose metabolism assessed by oral glucose tolerance test
Between-group difference in the change of ketone supply to the heart assessed by blood ketones
Between-group difference in the change of renal function assessed by Cr-51 EDTA clearance
Between-group difference in the change of uric acid
Between-group difference in the change of urine albumin/creatinine ratio
Between-group difference in the change of cardiac biomarkers assessed by plasma concentrations of MR-proADM and hs-cTnI
Between-group difference in the change of cardiac systolic and diastolic function including left ventricular global longitudinal strain and left ventricular ejection fraction assessed by transthoracic echocardiography at rest and during stress
Between-group difference in the change of cardiac hemodynamics during rest and sub-maximal exercise assessed by right heart catheterization including pulmonary capillary wedge pressure to cardiac index ratio
Between-group difference in the change of cardiac hemodynamics during rest and sub-maximal exercise assessed by right heart catheterization including left ventricular contractile reserve
Between-group difference in the change of health-related quality of life assessed by the questionnaire KCCQ
Between-group difference in the change of health-related quality of life assessed by the questionnaire EQ-5D-5L

Full Information

First Posted
June 21, 2017
Last Updated
January 31, 2020
Sponsor
Morten Schou
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1. Study Identification

Unique Protocol Identification Number
NCT03198585
Brief Title
Empagliflozin in Heart Failure Patients With Reduced Ejection Fraction
Acronym
Empire HF
Official Title
Empagliflozin in Heart Failure Patients With Reduced Ejection Fraction: A Randomized Clinical Trial (Empire HF)
Study Type
Interventional

2. Study Status

Record Verification Date
January 2020
Overall Recruitment Status
Completed
Study Start Date
June 29, 2017 (Actual)
Primary Completion Date
December 20, 2019 (Actual)
Study Completion Date
January 17, 2020 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
Morten Schou

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
Yes
Data Monitoring Committee
No

5. Study Description

Brief Summary
To assess the effect of Empagliflozin on cardiac biomarkers, cardiac function at rest and during stress, cardiac hemodynamics, renal function, metabolism, daily activity level and health-related quality of life in stable, symptomatic heart failure patients with reduced left ventricular ejection fraction. The primary hypothesis is that 3 months' treatment with Empagliflozin 10 mg a day will reduce the plasma concentrations of N-terminal pro-brain natriuretic peptide (NT-proBNP).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Heart Failure With Reduced Ejection Fraction

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
190 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Empagliflozin 10 mg
Arm Type
Active Comparator
Arm Title
Placebo
Arm Type
Placebo Comparator
Intervention Type
Drug
Intervention Name(s)
Empagliflozin 10 MG
Intervention Description
Capsule, once a day for 90 days
Intervention Type
Other
Intervention Name(s)
Placebo
Intervention Description
Capsule, once a day for 90 days
Primary Outcome Measure Information:
Title
Between-group difference in the change of plasma concentrations of NT-proBNP
Time Frame
90 days
Secondary Outcome Measure Information:
Title
Between-group difference in the change in daily activity level measured by patient-worn accelerometers as change in the amount of daily average accelerometer units
Time Frame
90 days
Title
Between-group difference in the change in body composition assessed by DXA scan
Time Frame
90 days
Title
Between-group difference in the change of estimated extracellular volume assessed by Cr-51 EDTA clearance
Time Frame
90 days
Title
Between-group difference in the change of estimated plasma volume assessed by hematocrit and hemoglobin
Time Frame
90 days
Title
Between-group difference in the change of glucose metabolism assessed by oral glucose tolerance test
Time Frame
90 days
Title
Between-group difference in the change of ketone supply to the heart assessed by blood ketones
Time Frame
90 days
Title
Between-group difference in the change of renal function assessed by Cr-51 EDTA clearance
Time Frame
90 days
Title
Between-group difference in the change of uric acid
Time Frame
90 days
Title
Between-group difference in the change of urine albumin/creatinine ratio
Time Frame
90 days
Title
Between-group difference in the change of cardiac biomarkers assessed by plasma concentrations of MR-proADM and hs-cTnI
Time Frame
90 days
Title
Between-group difference in the change of cardiac systolic and diastolic function including left ventricular global longitudinal strain and left ventricular ejection fraction assessed by transthoracic echocardiography at rest and during stress
Time Frame
90 days
Title
Between-group difference in the change of cardiac hemodynamics during rest and sub-maximal exercise assessed by right heart catheterization including pulmonary capillary wedge pressure to cardiac index ratio
Time Frame
90 days
Title
Between-group difference in the change of cardiac hemodynamics during rest and sub-maximal exercise assessed by right heart catheterization including left ventricular contractile reserve
Time Frame
90 days
Title
Between-group difference in the change of health-related quality of life assessed by the questionnaire KCCQ
Time Frame
90 days
Title
Between-group difference in the change of health-related quality of life assessed by the questionnaire EQ-5D-5L
Time Frame
90 days

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
85 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Optimal Heart Failure Therapy in accordance with European and National Guidelines LVEF ≤ 0.40 eGFR > 30 ml/min/1.73 m2 BMI < 45 kg/m2 NYHA class I-III Age > 18 years If T2D - optimal treatment in accordance with European and National Guidelines If T2D - stable doses of antiglycemic treatment for 30 days If T2D - HbA1C 6.5-10% Exclusion Criteria: CRT-D/-P implanted < 90 days Uncorrected severe valvular disease Non-compliance Use of metalozone NYHA IV Age > 85 years Dementia Admission for HF < 30 days Admission for hypoglycemia < 12 month Known sustained VT Symptomatic hypotension and systolic BP < 95 mmHg Unable to perform an exercise test Immobilization Pregnancy Participation in other medical trials Previous intolerance of Empagliflozin or excipients
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Morten Schou, MD
Organizational Affiliation
Herlev and Gentofte University Hospital
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Jacob E Moller, MD
Organizational Affiliation
Odense University Hospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
Herlev and Gentofte University Hospital
City
Copenhagen
ZIP/Postal Code
2730
Country
Denmark
Facility Name
Odense University Hospital
City
Odense
ZIP/Postal Code
5000
Country
Denmark

12. IPD Sharing Statement

Plan to Share IPD
No
Citations:
PubMed Identifier
35973031
Citation
Jensen J, Omar M, Kistorp C, Tuxen C, Poulsen MK, Faber J, Kober L, Gustafsson F, Moller JE, Schou M. Effect of Empagliflozin on Multiple Biomarkers in Heart Failure: Insights From the Empire Heart Failure Trial. Circ Heart Fail. 2022 Aug;15(8):e009333. doi: 10.1161/CIRCHEARTFAILURE.121.009333. Epub 2022 Apr 21. No abstract available.
Results Reference
derived
PubMed Identifier
35219331
Citation
Omar M, Jensen J, Kistorp C, Hojlund K, Videbaek L, Tuxen C, Larsen JH, Andersen CF, Gustafsson F, Kober L, Schou M, Moller JE. The effect of empagliflozin on growth differentiation factor 15 in patients with heart failure: a randomized controlled trial (Empire HF Biomarker). Cardiovasc Diabetol. 2022 Feb 27;21(1):34. doi: 10.1186/s12933-022-01463-2.
Results Reference
derived
PubMed Identifier
34743533
Citation
Omar M, Jensen J, Burkhoff D, Frederiksen PH, Kistorp C, Videbaek L, Poulsen MK, Gustafsson F, Kober L, Borlaug BA, Schou M, Moller JE. Effect of Empagliflozin on Blood Volume Redistribution in Patients With Chronic Heart Failure and Reduced Ejection Fraction: An Analysis From the Empire HF Randomized Clinical Trial. Circ Heart Fail. 2022 Mar;15(3):e009156. doi: 10.1161/CIRCHEARTFAILURE.121.009156. Epub 2021 Nov 8.
Results Reference
derived
PubMed Identifier
34509409
Citation
Omar M, Jensen J, Frederiksen PH, Videbaek L, Poulsen MK, Brond JC, Gustafsson F, Borlaug BA, Schou M, Moller JE. Hemodynamic Determinants of Activity Measured by Accelerometer in Patients With Stable Heart Failure. JACC Heart Fail. 2021 Nov;9(11):824-835. doi: 10.1016/j.jchf.2021.05.013. Epub 2021 Sep 8.
Results Reference
derived
PubMed Identifier
34061581
Citation
Jensen J, Omar M, Kistorp C, Tuxen C, Gustafsson I, Kober L, Gustafsson F, Faber J, Forman JL, Moller JE, Schou M. Metabolic Effects of Empagliflozin in Heart Failure: A Randomized, Double-Blind, and Placebo-Controlled Trial (Empire HF Metabolic). Circulation. 2021 Jun;143(22):2208-2210. doi: 10.1161/CIRCULATIONAHA.120.053463. Epub 2021 Jun 1. No abstract available.
Results Reference
derived
PubMed Identifier
33404637
Citation
Omar M, Jensen J, Ali M, Frederiksen PH, Kistorp C, Videbaek L, Poulsen MK, Tuxen CD, Moller S, Gustafsson F, Kober L, Schou M, Moller JE. Associations of Empagliflozin With Left Ventricular Volumes, Mass, and Function in Patients With Heart Failure and Reduced Ejection Fraction: A Substudy of the Empire HF Randomized Clinical Trial. JAMA Cardiol. 2021 Jul 1;6(7):836-840. doi: 10.1001/jamacardio.2020.6827.
Results Reference
derived
PubMed Identifier
33357505
Citation
Jensen J, Omar M, Kistorp C, Tuxen C, Gustafsson I, Kober L, Gustafsson F, Faber J, Malik ME, Fosbol EL, Bruun NE, Forman JL, Jensen LT, Moller JE, Schou M. Effects of empagliflozin on estimated extracellular volume, estimated plasma volume, and measured glomerular filtration rate in patients with heart failure (Empire HF Renal): a prespecified substudy of a double-blind, randomised, placebo-controlled trial. Lancet Diabetes Endocrinol. 2021 Feb;9(2):106-116. doi: 10.1016/S2213-8587(20)30382-X. Epub 2020 Dec 22.
Results Reference
derived
PubMed Identifier
31227014
Citation
Jensen J, Omar M, Kistorp C, Poulsen MK, Tuxen C, Gustafsson I, Kober L, Gustafsson F, Fosbol E, Bruun NE, Videbaek L, Frederiksen PH, Moller JE, Schou M. Empagliflozin in heart failure patients with reduced ejection fraction: a randomized clinical trial (Empire HF). Trials. 2019 Jun 21;20(1):374. doi: 10.1186/s13063-019-3474-5.
Results Reference
derived

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Empagliflozin in Heart Failure Patients With Reduced Ejection Fraction

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