Clinical trial NCT03198585: Empagliflozin in Heart Failure Patients With Reduced Ejection Fraction
Official title: Empagliflozin in Heart Failure Patients With Reduced Ejection Fraction: A Randomized Clinical Trial (Empire HF)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Heart Failure With Reduced Ejection Fraction
Lead sponsor: Herlev and Gentofte Hospital
Sponsor class: OTHER
First posted: 2017-06-26
Enrollment: 190
Sex: ALL
Minimum age (years): 18
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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).


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

Primary outcomes:
measure: Between-group difference in the change of plasma concentrations of NT-proBNP
timeFrame: 90 days
Secondary outcomes:
measure: 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
timeFrame: 90 days
measure: Between-group difference in the change in body composition assessed by DXA scan
timeFrame: 90 days
measure: Between-group difference in the change of estimated extracellular volume assessed by Cr-51 EDTA clearance
timeFrame: 90 days
measure: Between-group difference in the change of estimated plasma volume assessed by hematocrit and hemoglobin
timeFrame: 90 days
measure: Between-group difference in the change of glucose metabolism assessed by oral glucose tolerance test
timeFrame: 90 days
measure: Between-group difference in the change of ketone supply to the heart assessed by blood ketones
timeFrame: 90 days
measure: Between-group difference in the change of renal function assessed by Cr-51 EDTA clearance
timeFrame: 90 days
measure: Between-group difference in the change of uric acid
timeFrame: 90 days
measure: Between-group difference in the change of urine albumin/creatinine ratio
timeFrame: 90 days
measure: Between-group difference in the change of cardiac biomarkers assessed by plasma concentrations of MR-proADM and hs-cTnI
timeFrame: 90 days
measure: 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
timeFrame: 90 days
measure: 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
timeFrame: 90 days
measure: 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
timeFrame: 90 days
measure: Between-group difference in the change of health-related quality of life assessed by the questionnaire KCCQ
timeFrame: 90 days
measure: Between-group difference in the change of health-related quality of life assessed by the questionnaire EQ-5D-5L
timeFrame: 90 days
Other outcomes:
Locations:
city: Copenhagen
country: Denmark
facility: Herlev and Gentofte University Hospital
city: Odense
country: Denmark
facility: Odense University Hospital
Study officials:
affiliation: Herlev and Gentofte University Hospital
name: Morten Schou, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Odense University Hospital
name: Jacob E Moller, MD
role: PRINCIPAL_INVESTIGATOR
References:
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.
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.
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.
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.
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.
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.
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.
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.