ENAVOgliflozin Outcome Trial in Patients With Severe Aortic Stenosis After Transcatheter Aortic Valve Replacement

Exclusion Criteria25

• Acute decompensated Heart Failure (exacerbation of chronic Heart Failure) requiring intravenous diuretics, vasodilators, inotropic agents, or mechanical support, or hemodynamic instability following the transcatheter aortic valve replacement procedure.
• Currently receiving therapy with an SGLT2 inhibitor within 4 weeks prior to randomization; discontinuation of current use of SGLT2 inhibitor for the purposes of study enrolment is not permitted.
• Known allergy, hypersensitivity, or previous intolerance to an SGLT2 inhibitors.
• HF with reduced ejection fraction (LVEF \<40%).
• Type 1 diabetes mellitus or diabetes ketoacidosis.
• Chronic cystitis and/or recurrent urinary tract infection (≥2 times within 1 year).
• Stroke or transient ischemic attack within 12 weeks prior to enrollment.
• Symptomatic persistent hypotension and/or a systolic blood pressure (SBP) \< 95 mm Hg at screening or at randomization.
• SBP ≥180 mmHg irrespective of treatment or SBP ≥160 mmHg with at least ≥3 antihypertensive drugs at screening or randomization.
• Heart failure due to any of the following causes; known infiltrative cardiomyopathy (e.g. amyloid, sarcoid, lymphoma, endomyocardial fibrosis, haemochromatosis, Fabry disease), active myocarditis, constrictive pericarditis, cardiac tamponade, known hypertrophic obstructive cardiomyopathy, arrhythmogenic right ventricular cardiomyopathy/dysplasia (ARVD), or uncorrected primary valvular disease.
• Severe renal insufficiency (eGFR \<30 ml/min/1.73 m2 of body-surface area based on the Modification of Diet in Renal Disease (MDRD) formula) or end-stage renal disease or requiring dialysis at the time of screening.
• Acute or chronic liver disease with severe impairment of liver function (e.g., ascites, esophageal varices, coagulopathy) or serum levels of transminases or alkaline phosphatase more than two times the upper limit of normal at screening.
• Chronic pulmonary disease requiring home oxygen, oral steroid therapy or hospitalization for exacerbation within 12 months, or significant chronic pulmonary disease in the Investigator's opinion, or primary pulmonary arterial hypertension.
• Current or suspicious malignancy or history of malignancy within 5 years
• Uncontrolled anaemia or haemoglobin \<9g/dl
• Uncontrolled hypothyroidism or arrhythmia or tachycardia
• Current ongoing alcoholic or drug addict
• Subjects with non-cardiac co-morbidities with life expectancy less than 12 months
• Planned major high-risk operation after transcatheter aortic valve replacement (TAVR)
• Women of childbearing age who have not reached a consensus on the use of highly effective contraception. Pregnancy or breastfeeding.
• Participation in other clinical trials, However, where at least one or more conditions are satisfied, it could be an exception according to an investigator's discretion;
• Participating in the observational study expected no effect on the safety and/or effectiveness evaluation of this trial.
• Screening failed before any interventional factor is involved.
• Participants who have completed their involvement in clinical trials and have surpassed a 4-week period since their last administration of the investigational drug.
• Participated in academic trials like strategic or medical device comparison studies conducted under standard therapy provided that there is no additional risk or a specific procedure to a subject and no interference between this trial and other studies.