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

NCT05672836 | Recruiting Phase 4 DMC

• 1 other identifier: AMCCV2023-01
• Study Type: interventional
• Target: 1,040
• Locations: 1 country
• Sites: 31

Brief Summary

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.

Conditions

Aortic Valve Stenosis; Heart Failure

Keywords

Transcatheter Aortic Valve Implantation; heart failure with preserved ejection fraction; Sodium-glucose cotransporter-2 inhibitor; transcatheter aortic valve replacement

Outcome Measures

Primary Outcomes (1)

• 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

Secondary Outcomes (10)

• Event rate of death from any cause

  12 months

• Event rate of nonfatal myocardial infarction

  12 months

• Event rate of nonfatal stroke

  12 months

• Event rate of hospitalization for heart failure

  12 months

• Event rate of Composite renal endpoint

  12 months

Study Arms (2)

Enavogliflozin Group

EXPERIMENTAL

0.3 mg 1 tablet once daily

Drug: Enavogliflozin

placebo as add-on to standard of care treatment group

PLACEBO COMPARATOR

Placebo matching enavogliflozin

Drug: Standard-of-Care

Interventions

Enavogliflozin DRUG

0.3 mg 1 tablet once daily

Enavogliflozin Group

Standard-of-Care DRUG

Standard-of-Care medical therapy plus Enavogliflozin matching placebo

Also known as: Standard-of-Care medical therapy

placebo as add-on to standard of care treatment group

Eligibility Criteria

• Age: 19 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• \. 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:
• correct positioning of a single prosthetic heart valve into the proper anatomical location AND
• intended performance of the prosthetic heart valve (mean aortic valve gradient \<20 mmHg, peak velocity \<3 m/s, no moderate or severe prosthetic valve regurgitation) AND
• absence of periprocedural complications (any type of stroke, life-threatening bleeding, acute coronary artery obstruction requiring intervention, major vascular complication requiring intervention, unresolved acute valve thrombosis, or any requirement of a repeat procedure).
• \. 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).
• \. Patients who voluntarily participated in the written agreement

You may not qualify if:

• 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

Sponsors & Collaborators

• Duk-Woo Park, MD: lead
• CardioVascular Research Foundation, Korea: collaborator
• Daewoong Pharmaceutical Co. LTD.: collaborator

Study Sites (31)

Bucheon Sejong Hospital

Bucheon-si, South Korea

RECRUITING

Gyeongsang National University Changwon Hospital

Changwon, South Korea

RECRUITING

Daegu Catholic University Medical Center

Daegu, South Korea

RECRUITING

Keimyung University Dongsan Medical Center

Daegu, South Korea

RECRUITING

Kyungpook National University Hospital

Daegu, South Korea

RECRUITING

Yeungnam University Medical Center

Daegu, South Korea

NOT YET RECRUITING

Chungnam National University Hospital

Daejeon, South Korea

RECRUITING

The Catholic University of Korea, Daejeon ST. Mary's Hospital

Daejeon, South Korea

RECRUITING

Gangneung Asan Hospital

Gangneung, South Korea

RECRUITING

Chonnam National University Hospital

Gwangju, South Korea

RECRUITING

Inje University Ilsan Paik Hospital

Ilsan, South Korea

RECRUITING

Gachon University Gil Hospital

Incheon, South Korea

RECRUITING

Incheon Sejong Hospital

Incheon, South Korea

RECRUITING

Inha University Hospital

Incheon, South Korea

RECRUITING

The Catholic University of Korea, Incheon St. Mary's Hospital

Incheon, South Korea

RECRUITING

Dong-A Medical Center

Pusan, South Korea

RECRUITING

Inje University Pusan Paik Hospital

Pusan, South Korea

RECRUITING

Pusan National University Hospital

Pusan, South Korea

RECRUITING

Seoul university Bundang hospital

Seongnam-si, South Korea

NOT YET RECRUITING

Asan Medical Center

Seoul, South Korea

RECRUITING

Ewha Womans University Mokdong Hospital

Seoul, South Korea

RECRUITING

Ewha Womans University Seoul Hospital

Seoul, South Korea

RECRUITING

Hanyang University Seoul Hospital

Seoul, South Korea

RECRUITING

Konkuk University Medical Center

Seoul, South Korea

RECRUITING

Korea University Anam Hospital

Seoul, South Korea

RECRUITING

Korea University Guro Hospital

Seoul, South Korea

RECRUITING

SNU Boramae Medical Center

Seoul, South Korea

RECRUITING

The Catholic Univ. of Korea Eunpyeong St. Mary's hospital

Seoul, South Korea

RECRUITING

The Catholic University of Korea, ST. Vincent's Hospital

Suwon, South Korea

RECRUITING

Uijeongbu Eulji Medical Center, Eulji University

Uijeongbu-si, South Korea

NOT YET RECRUITING

Ulsan University Hospital

Ulsan, South Korea

RECRUITING

MeSH Terms

Conditions

Aortic Valve Stenosis; Heart Failure

Interventions

Enavogliflozin; Standard of Care

Condition Hierarchy (Ancestors)

Aortic Valve Disease; Heart Valve Diseases; Heart Diseases; Cardiovascular Diseases; Ventricular Outflow Obstruction

Intervention Hierarchy (Ancestors)

Quality Indicators, Health Care; Quality of Health Care; Health Services Administration; Health Care Quality, Access, and Evaluation

Study Officials

• Seung-jung Park, MD

  Professor, Cardiology, Asan Medical Center Heart Institute, Valvular Heart Disease Center, Ischemic Heart Disease Center

  STUDY CHAIR

Central Study Contacts

Jeong-youn Bae, Project manager

CONTACT

82230107259; cvcrc10@amc.seoul.kr

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor, Cardiology, Asan Medical Center Heart Institute, Valvular Heart Disease Center, Ischemic Heart Disease Center

Study Record Dates

• First Submitted: January 1, 2023
• First Posted: January 5, 2023
• Study Start: December 18, 2024
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): April 1, 2027
• Last Updated: December 15, 2025

Record last verified: 2025-12

Locations

KR (31)