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| Name | Class |
|---|---|
| CardioVascular Research Foundation, Korea | OTHER |
| Daewoong Pharmaceutical Co. LTD. | INDUSTRY |
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The goal of this trial is to to determine whether use of a novel SGLT2 inhibitor, Enavogliflozin 0.3 mg once daily is superior to placebo, when added to standard-of-care, in reducing the composite of major cardiovascular events and Heart Failure events (hospitalization for Heart Failure or urgent Heart Failure visit) among patients who underwent transcatheter aortic valve replacement for severe aortic stenosis and with heart failure with preserved ejection fraction.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Enavogliflozin Group | Experimental | 0.3 mg 1 tablet once daily |
|
| placebo as add-on to standard of care treatment group | Placebo Comparator | Placebo matching enavogliflozin |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Enavogliflozin | Drug | 0.3 mg 1 tablet once daily |
| |
| Measure | Description | Time Frame |
|---|---|---|
| Time from randomization to first occurrence of a composite of major adverse cardiovascular events* or hospitalization for heart failure | Time from randomization to the first occurrence of a composite of major adverse cardiovascular events* or hospitalization for heart failure at 12 months after randomization. *Major adverse cardiovascular events included death from any causes, nonfatal myocardial infarction, or nonfatal stroke. A composite endpoint is an endpoint that is a combination of multiple clinical endpoints. An event is considered to have occurred if any one of several different events is observed. | 12 months |
| Measure | Description | Time Frame |
|---|---|---|
| Event rate of death from any cause | 12 months | |
| Event rate of nonfatal myocardial infarction | 12 months | |
| Event rate of nonfatal stroke |
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Inclusion Criteria:
1. Patients aged ≥19 with symptomatic aortic stenosis who underwent successful transcatheter aortic valve replacement (TAVR)* (either native valve or valve in valve with any approved/marketed device).
* A successful TAVI is defined as device success according to the VARC-2(Valve Academic Research Consortium 2) and VARC-3 criteria:
2. Heart Failure with Mildly Reduced or Preserved Ejection Fraction
Left ventricular ejection fraction (LVEF) ≥40%
structural heart disease_Left ventricular hypertrophy (LVH) or Left atrial enlargement
A. Left ventricular hypertrophy (LVH) with septal thickness or posterior wall thickness ≥ 1.1 cm or
B. Left atrial (LA) enlargement with at least one of the following: LA width (diameter) ≥3.8 cm or LA length ≥ 5.0 cm, or LA area ≥ 20cm2, or LA volume ≥ 55mL or LA volume index ≥ 29mL/m.
NT-proBNP ≥ 300 pg/mL (for patients without ongoing atrial fibrillation) or NT-proBNP must be ≥ 600 pg/mL (for patients with ongoing atrial fibrillation).
3. Patients who voluntarily participated in the written agreement
Exclusion Criteria:
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;
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Jeong-youn Bae, Project manager | Contact | 82230107259 | cvcrc10@amc.seoul.kr |
| Name | Affiliation | Role |
|---|---|---|
| Seung-jung Park, MD | Professor, Cardiology, Asan Medical Center Heart Institute, Valvular Heart Disease Center, Ischemic Heart Disease Center | Study Chair |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Bucheon Sejong Hospital | Recruiting | Bucheon-si | South Korea |
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| Standard-of-Care |
| Drug |
Standard-of-Care medical therapy plus Enavogliflozin matching placebo |
|
|
| 12 months |
| Event rate of hospitalization for heart failure | 12 months |
| Event rate of Composite renal endpoint | Composite renal endpoint, defined as time to first occurrence of (1) chronic dialysis; (2) renal transplantation; (3) sustained reduction of ≥40% in estimated glomerular filtration rate (GFR); or (4) sustained estimated GFR <15 mL/min/1.73 m2 for patients with baseline estimated GFR ≥30 mL/min/1.73 m2. | 12 months |
| Event rate of Rehospitalization for any reason | 12 months |
| Changes in measures of cardiac volume and function assessed by serial echocardiography | left ventricular ejection fraction(LVEF), LV end-diastolic volume index (LVEDVI), LV end-systolic volume index (LVESVI), left atrial volume index (LAVI), and the ratio of early transmitral Doppler velocity/early diastolic annular velocity (E/e') | 12 months |
| Changes in New York Heart Association (NYHA) functional class and the Kansas City Cardiomyopathy Questionnaire (KCCQ) summary score | New York Heart Association (NYHA) Functional Classification on a scale from I to IV, with higher scores indicating severe symptoms and physical limitations associated with heart failure. the Kansas City Cardiomyopathy Questionnaire (KCCQ)on a scale from 0 to 100, with higher scores indicating fewer symptoms and physical limitations associated with heart failure. | 12 months |
| Serial change in NT-proBNP | N-terminal (NT)-pro hormone BNP (NT-proBNP) | 12 months |
| Event rate of the safety events | The safety events are defined as;
| 12 months |
| Gyeongsang National University Changwon Hospital | Recruiting | Changwon | South Korea |
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| Daegu Catholic University Medical Center | Recruiting | Daegu | South Korea |
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| Keimyung University Dongsan Medical Center | Recruiting | Daegu | South Korea |
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| Kyungpook National University Hospital | Recruiting | Daegu | South Korea |
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| Yeungnam University Medical Center | Withdrawn | Daegu | South Korea |
| Chungnam National University Hospital | Recruiting | Daejeon | South Korea |
|
| The Catholic University of Korea, Daejeon ST. Mary's Hospital | Recruiting | Daejeon | South Korea |
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| Gangneung Asan Hospital | Recruiting | Gangneung | South Korea |
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| Chonnam National University Hospital | Recruiting | Gwangju | South Korea |
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| Inje University Ilsan Paik Hospital | Recruiting | Ilsan | South Korea |
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| Gachon University Gil Hospital | Recruiting | Incheon | South Korea |
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| Incheon Sejong Hospital | Recruiting | Incheon | South Korea |
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| Inha University Hospital | Recruiting | Incheon | South Korea |
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| The Catholic University of Korea, Incheon St. Mary's Hospital | Recruiting | Incheon | South Korea |
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| Dong-A Medical Center | Recruiting | Pusan | South Korea |
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| Inje University Pusan Paik Hospital | Recruiting | Pusan | South Korea |
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| Pusan National University Hospital | Recruiting | Pusan | South Korea |
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| Seoul university Bundang hospital | Recruiting | Seongnam-si | South Korea |
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| Asan Medical Center | Recruiting | Seoul | South Korea |
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| Ewha Womans University Mokdong Hospital | Recruiting | Seoul | South Korea |
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| Ewha Womans University Seoul Hospital | Recruiting | Seoul | South Korea |
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| Hanyang University Seoul Hospital | Recruiting | Seoul | South Korea |
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| Konkuk University Medical Center | Recruiting | Seoul | South Korea |
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| Korea University Anam Hospital | Recruiting | Seoul | South Korea |
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| Korea University Guro Hospital | Recruiting | Seoul | South Korea |
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| SNU Boramae Medical Center | Recruiting | Seoul | South Korea |
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| The Catholic Univ. of Korea Eunpyeong St. Mary's hospital | Recruiting | Seoul | South Korea |
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| The Catholic University of Korea, ST. Vincent's Hospital | Withdrawn | Suwon | South Korea |
| Uijeongbu Eulji Medical Center, Eulji University | Withdrawn | Uijeongbu-si | South Korea |
| Ulsan University Hospital | Recruiting | Ulsan | South Korea |
|
| ID | Term |
|---|---|
| D001024 | Aortic Valve Stenosis |
| D006333 | Heart Failure |
| ID | Term |
|---|---|
| D000082862 | Aortic Valve Disease |
| D006349 | Heart Valve Diseases |
| D006331 | Heart Diseases |
| D002318 | Cardiovascular Diseases |
| D014694 | Ventricular Outflow Obstruction |
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| ID | Term |
|---|---|
| C000729921 | Enavogliflozin |
| D059039 | Standard of Care |
| ID | Term |
|---|---|
| D019984 | Quality Indicators, Health Care |
| D011787 | Quality of Health Care |
| D006298 | Health Services Administration |
| D017530 | Health Care Quality, Access, and Evaluation |
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