The study is a randomized, placebo-controlled, and double-blinded trial in patients with aortic stenosis (AS) undergoing aortic valve replacement (AVR). After AVR, patients will be randomized 1:1 to empagliflozin (SGLT2i) or placebo to investigate whether empagliflozin is superior to placebo in reducing left ventricular mass and improve symptoms to 6 months.
In this randomized, placebo-controlled, and double-blinded trial we investigate whether empagliflozin (SGLT2i) is superior to placebo in reducing left ventricular mass and improve symptoms. All patients with AS who are referred to Rigshospitalet for AVR (both surgical and transcatheter approaches) will be screened for in- and exclusion criteria in the medical record based on the Danish Health Act §46 by the PI, co-PI, or a delegated study nurse. If the patient fulfills the inclusion criteria and none of the exclusions criteria, the patient is invited to participate in the study. Included patients will be randomized 1:1 in blocks of 2, 4, and 6 patients to either Empagliflozin 10 mg daily or placebo. Point of randomization will be in the hospital when the patients has undergone AVR. The total treatment period is 6 months with either 10 mg Empagliflozin or placebo. The trial participants will receive conventional treatment, which will be carried out irrespective of the inclusion in the trial in accordance with national guidelines. Routine clinical check-ups irrespective of the trial setup will be performed at 3 months after discharge, and study-outcomes will be assessed at discharge, 3 months, and 6 months (eg. echocardiography). Blood samples (including N-Terminal-proBNP, renal function and electrolytes, hemoglobin and HbA1c) will be part of such routine visits as well as a standardized symptom-scoring tool (KCCQ and NYHA classification). Compliance will be evaluated at 1-, 3- and 6-months. The assessment for 1-month will be per telephone and the assessment at 3- and 6-months will be at the routine clinical check-ups in the outpatient clinic. The CT scan performed in the planning of the procedure will be used for the baseline assessment (before AVR). An identical exam (CT scan) will be performed at 6 months to assess change in LV mass.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
205
10 mg empagliflozin daily for six months
Placebo capsule once daily for six months
University Hospital of Copenhagen, Rigshospitalet
Copenhagen, Denmark
Change in left ventricular mass indexed to body surface area
Change in left ventricular mass indexed to body surface area (measured by CT) from pre-Aortic Valve Replacement to 6-months post-Aortic Valve Replacement
Time frame: 6 months from discharge post-Aortic Valve Replacement
LVESVi
Left ventricular end-systolic volume indexed to body surface (LVESVi) (measured by CT)
Time frame: 6-months from discharge post-aortic valve replacement
LV GLS (echo)
Left ventricular global longitudinal strain (LV GLS) (measured by echocardiography)
Time frame: 3- and 6-months from discharge
N-terminal pro B-type natriuretic peptide (NT-proBNP) change
NT-proBNP change from baseline to 6 months
Time frame: 3- and 6-months from discharge
Death and readmission for any non-planned cause
A composite outcome of death and readmission for any non-planned cause
Time frame: 6 months from discharge date (after aortic valve replacement)
Death
Death during follow-up, from discharge to 6-months after discharge
Time frame: 6 months from discharge date (after aortic valve replacement)
Readmission for any cause
Readmission for any cause to any hospital after discharge
Time frame: 6 months from discharge date (after aortic valve replacement)
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Admission for heart failure
Admission for heart failure to any hospital
Time frame: 6 months from discharge date (after aortic valve replacement)
Kansas City Cardiomyopathy Questionaire (KCCQ)
Change in symptom score (KCCQ) at 6-months. KCCQ scores are scaled from 0 to 100, where scores represent health status as follows: 0-24: very poor to poor; 25-49: poor to fair; 50-74: fair to good; and 75-100: good to excellent. In this study a change of 5 points is considered a meaningful change.
Time frame: 6 months from discharge date (after aortic valve replacement)
Quality of Life (QoL) - The Minnesota Living with Heart Failure Questionnaire (MLHFQ)
Quality of life assessment at baseline and 6 months after discharge post-AVR using the Minnesota Living with Heart Failure Questionnaire (MLHFQ). MLHFQ consist of 21 questions. The response format ranges from 0 (none or not applicable), to 1 (very little) to 5 (very much). The sum of responses ranges from 0 to 105. The score increases with adverse impact of the disease on the respondent's life.
Time frame: 6 months from discharge date (after aortic valve replacement)
New York Heart Association (NYHA) Functional Classification
Change in symptom score at 6 months (NYHA classification). The NYHA classification places patients in one of four categories based on limitations of physical activity. Class I: No limitation of physical activity; Class II: Slight limitation of physical activity; Class III: Marked limitation of physical activity; Class IV: Symptoms of heart failure at rest.
Time frame: 3- and 6-months from discharge date (after aortic valve replacement)