MedPath

EMPagliflozin After Aortic Valve Replacement

Phase 4
Recruiting
Conditions
Aortic Valve Stenosis
Interventions
Drug: Placebo
Registration Number
NCT06171802
Lead Sponsor
Rigshospitalet, Denmark
Brief Summary

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.

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.

Recruitment & Eligibility

Status
RECRUITING
Sex
All
Target Recruitment
205
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 & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
PlaceboPlacebo1 capsule of placebo, once daily for six months
EmpagliflozinEmpagliflozinEmpagliflozin 1 capsule of 10 mg, once daily for six months.
Primary Outcome Measures
NameTimeMethod
Change in left ventricular mass indexed to body surface area6 months from discharge post-Aortic Valve Replacement

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

Secondary Outcome Measures
NameTimeMethod
LVESVi6-months from discharge post-aortic valve replacement

Left ventricular end-systolic volume indexed to body surface (LVESVi) (measured by CT)

LV GLS (echo)3- and 6-months from discharge

Left ventricular global longitudinal strain (LV GLS) (measured by echocardiography)

Quality of Life (QoL) - The Minnesota Living with Heart Failure Questionnaire (MLHFQ)6 months from discharge date (after aortic valve replacement)

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.

N-terminal pro B-type natriuretic peptide (NT-proBNP) change3- and 6-months from discharge

NT-proBNP change from baseline to 6 months

Death and readmission for any non-planned cause6 months from discharge date (after aortic valve replacement)

A composite outcome of death and readmission for any non-planned cause

Death6 months from discharge date (after aortic valve replacement)

Death during follow-up, from discharge to 6-months after discharge

Readmission for any cause6 months from discharge date (after aortic valve replacement)

Readmission for any cause to any hospital after discharge

Admission for heart failure6 months from discharge date (after aortic valve replacement)

Admission for heart failure to any hospital

Kansas City Cardiomyopathy Questionaire (KCCQ)6 months from discharge date (after aortic valve replacement)

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.

New York Heart Association (NYHA) Functional Classification3- and 6-months from discharge date (after aortic valve replacement)

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.

Trial Locations

Locations (1)

University Hospital of Copenhagen, Rigshospitalet

🇩🇰

Copenhagen, Denmark

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