EMPagliflozin After Aortic Valve Replacement (EMPAVR)

EMPagliflozin After Aortic Valve Replacement - The EMPAVR Study - A Randomized Clinical Trial

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.

Study Overview

• Status: Completed
• Conditions: Aortic Valve Stenosis
• Intervention / Treatment: Drug: Empagliflozin; Drug: Placebo

Detailed Description

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
• Enrollment (Actual): 206
• Phase: Phase 4

Contacts and Locations

Study Locations

• Denmark
  • Copenhagen, Denmark, 2100
    • University Hospital of Copenhagen, Rigshospitalet

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

Severe symptomatic aortic stenosis AND Surgical or transcatheter aortic valve replacement within 14 days

Exclusion Criteria:

• Prior treatment with a SGLT2i
• Left ventricular ejection fraction < 45%
• Estimated Glomerular Filtration Rate (eGFR) < 30 mL/min
• Hypersensitivity to empagliflozin or placebo tablet
• Type I Diabetes
• Patients who do not understand Danish or English
• Women who are pregnant or are nursing or plan to become pregnant during trial

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Empagliflozin; Empagliflozin 1 capsule of 10 mg, once daily for six months.	Drug: Empagliflozin; 10 mg empagliflozin daily for six months; Other Names: Jardiance
Placebo Comparator: Placebo; 1 capsule of placebo, once daily for six months	Drug: Placebo; Placebo capsule once daily for six months

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	6 months from discharge post-Aortic Valve Replacement

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
LVESVi	Left ventricular end-systolic volume indexed to body surface (LVESVi) (measured by CT)	6-months from discharge post-aortic valve replacement
LV GLS (echo)	Left ventricular global longitudinal strain (LV GLS) (measured by echocardiography)	3- and 6-months from discharge
N-terminal pro B-type natriuretic peptide (NT-proBNP) change	NT-proBNP change from baseline to 6 months	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	6 months from discharge date (after aortic valve replacement)
Death	Death during follow-up, from discharge to 6-months after discharge	6 months from discharge date (after aortic valve replacement)
Readmission for any cause	Readmission for any cause to any hospital after discharge	6 months from discharge date (after aortic valve replacement)
Admission for heart failure	Admission for heart failure to any hospital	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.	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.	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.	3- and 6-months from discharge date (after aortic valve replacement)

Collaborators and Investigators

• Sponsor: Rigshospitalet, Denmark
• Investigators: Principal Investigator: Emil L. Fosbøl, MD, PhD, University Hospital of Copenhagen - Rigshospitalet

Publications and helpful links

General Publications

• Sorensen LM, Reinert MS, Raja AA, de Backer O, Bieliauskas G, Schou M, Jensen J, Moller ELR, Linde JJ, Kofoed KF, Kuhl JT, Procida K, Petersen JK, Havers-Borgersen E, Kober L, Fosbol E. Design and rationale of the EMPagliflozin after Aortic Valve Replacement (EMPAVR) study: A randomized clinical trial. Am Heart J. 2026 Mar 27;297:107432. doi: 10.1016/j.ahj.2026.107432. Online ahead of print.

Study record dates

Study Major Dates

• Study Start (Actual): February 14, 2024
• Primary Completion (Actual): May 8, 2026
• Study Completion (Actual): May 18, 2026

Study Registration Dates

• First Submitted: November 23, 2023
• First Submitted That Met QC Criteria: December 6, 2023
• First Posted (Actual): December 15, 2023

Study Record Updates

• Last Update Posted (Actual): May 22, 2026
• Last Update Submitted That Met QC Criteria: May 19, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: Empagliflozin; Aortic Valve Replacement; Aortic Valve Stenosis; SGLT2i; Aortic Valve; Transcatheter Aortic Valve Implantation; Sodium-Glucose Cotransporter-2 inhibitor
• Additional Relevant MeSH Terms: Aortic Valve Disease; Cardiovascular Diseases; Heart Diseases; Heart Valve Diseases; Ventricular Outflow Obstruction; Aortic Valve Stenosis; Sodium-Glucose Transporter 2 Inhibitors; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Hypoglycemic Agents; empagliflozin
• Other Study ID Numbers: 2023-504731-40-01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• 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.: No