Tricuspid RegurgitationPhase 3EVENTNCT06027307
Enavogliflozin Outcome Trial in Functional Tricuspid Regurgitation
A Phase 3 study testing Enavogliflozin in people with Tricuspid Regurgitation and Heart Failure With Preserved Ejection Fraction, run by Asan Medical Center at 5 sites in South Korea.
Trial summary
The Enavogliflozin Outcome Trial in Functional Tricuspid Regurgitation (EVENT) was designed to examine the hypothesis that, compared with placebo, therapy with the SGLT2 inhibitor enavogliflozin would improve clinical and echocardiographic outcomes in heart failure (HF) patients with functional tricuspid regurgitation… Read more about this study
- Who is it for?
- Ages 20 to 80 years
- Conditions the study is for
- Tricuspid Regurgitation, Heart Failure With Preserved Ejection Fraction
- What is being tested?
- Enavogliflozin
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 541 participants
- Where
- 5 sitesSouth Korea
- Study dates
- 25 Oct 2023to Aug 2027
- Phase
- Phase 3
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 20 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients must agree to the study protocol and provide written informed consent
- Outpatients male or female between the age of 20 and 80
- Non-diabetic or type2 DM patients with HbA1c 6.5-10.5%
- HF with dyspnea of NYHA functional class II or III
- Presence of moderate or severe functional TR and preserved LVEF on echocardiography
- TR whose vena contracta ≥ 0.3cm, effective regurgitant orifice area ≥ 0.20 cm2, or jet area > 10cm2
- LVEF ≥ 50%
- NT-proBNP >125 pg/mL or BNP ≥35 pg/mL
Who cannot join
- History of hypersensitivity or allergy to the study drugs, drugs of similar chemical classes, as well as known or suspected contraindications to the study drug
- Current use or prior use of a SGLT-2 inhibitor or combined SGLT-1 and 2 inhibitor
- Any evidence of structural tricuspid valve disease
- Any significant left-sided valve disease
- Left ventricular ejection fraction <50%
- Marked bradycardia or 2nd or 3rd degree AV block
Show all 22Show fewer
- Intracardiac devices (CRT, ICD, Pacemaker)
- Hypertrophic or restrictive cardiomyopathy
- Severe pulmonary hypertension: TR Vmax > 3.5m/s at screening
- Medical history of hospitalization within 4 weeks
- Current acute decompensated heart failure or dyspnea of NYHA functional class IV
- Symptomatic hypotension and/or a SBP < 90 mmHg at screening
- Uncontrolled hypertension (SBP≥180mmHg or DBP≥110mmHg)
- Estimated GFR < 30 mL/min/1.73m2
- History of ketoacidosis
- Evidence of hepatic disease as determined by any one of the following: AST or ALT values exceeding 2 x upper limit of normal (ULN) at screening visit (Visit 0), history of hepatic encephalopathy, history of esophageal varices, or history of portocaval shunt.
- Acute coronary syndrome, stroke, major CV surgery, PCI within 3 months
- Plan for cardiac surgery, PCI or ablation of atrial flutter of fibrillation
- History of severe pulmonary disease
- Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, unless they are using a barrier method plus a hormonal method
- Pregnant or nursing (lactating) women
- Any clinically significant abnormality identified at the screening visit, physical examination, laboratory tests, or electrocardiogram which, in the judgment of the investigator, would preclude safe completion of the study
Trial locations and contacts
5 sites in 1 country.
5 sites in 1 country
South Korea5 sites
Inha University Hospital
Incheon
Asan Medical Center
Seoul
Samsung Medical Center
Seoul
Seoul National University Hospital
Seoul
Yonsei University Medical Center
Seoul
About this study
Official title: Multicenter, Randomized, Double-blind, Placebo-controlled Study to Assess the Effects of Enavogliflozin on Outcomes in Patients With Functional Tricuspid Regurgitation and Heart Failure With Preserved Left Ventricular Ejection Fraction
The Enavogliflozin Outcome Trial in Functional Tricuspid Regurgitation (EVENT) was designed to examine the hypothesis that, compared with placebo, therapy with the SGLT2 inhibitor enavogliflozin would improve clinical and echocardiographic outcomes in heart failure (HF) patients with functional tricuspid regurgitation (TR) and preserved left ventricular ejection fraction (LVEF).
The primary objective of the EVENT study is to test the hypothesis that, compared with placebo, therapy with enavogliflozin for 18 months would improve a composite of cardiovascular events or worsening of TR on follow-up echocardiography in HF patients with functional TR and preserved LVEF. The secondary objective is to examine whether enavogliflozin is effective in reduction of renal events and tricuspid regurgitation, and to evaluate whether beneficial effects of enavogliflozin on primary outcomes are associated with reduction of all-cause mortality.
Read the detailed description
Functional tricuspid regurgitation (TR) develops due to functional and structural alterations related to heart failure (HF), mitral valve disease and atrial fibrillation. An increase in cardiac filling pressure due to left ventricular (LV) systolic or diastolic dysfunction leads to left atrial, right atrial (RA) and right ventricular (RV) remodeling, which causes tricuspid annular dilatation and TR. The development of significant functional TR causes RV dysfunction and further dilation of RV, which deteriorates TR. Functional TR may occur with HF with preserved or reduced ejection fraction (EF), and the prevalence of moderate-to-severe functional TR is around 19% in patients with HF. Regardless of LVEF or pulmonary artery pressure, presence of moderate or severe functional TR is associated with more symptoms, reduced cardiac output, and worse renal function. A vicious cycle of significant TR, RV volume overload, adverse remodeling of RA, RV, and tricuspid annulus, and consequent aggravation of TR is suggested as a pathophysiologic mechanism of the poor clinical outcomes of patients with TR, and the presence of moderate or severe functional TR is a strong independent determinant of mortality in patients with HF. Because functional TR has a strong prognostic impact and plays an important pathophysiologic role in patients with HF, functional TR is suggested as a therapeutic target in HF. However, there have been no proven medical therapies for TR and only loop diuretics are cautiously recommended for relief of congestive symptoms in patients with severe TR and signs of RV failure. In patients with functional TR associated with systolic dysfunction, medical therapy for HF with a reduced EF may diminish functional TR by improving LV systolic function. Otherwise, the morbidity and mortality of patients with functional TR remain high and a novel therapeutic agent is needed to improve clinical outcomes of HF patients with functional TR and a preserved LV ejection fraction.
Sodium-glucose co-transporter 2 (SGLT2) inhibitors induce urinary excretion of glucose and sodium by blocking the SGLT2 transporter in the proximal tubule (8). SGLT2 inhibitor-induced natriuresis lower cardiac preload and reduce pulmonary congestion and systemic edema. SGLT2 inhibitors also restore tubuloglomerular feedback and lower the intraglomerular pressure by vasoconstriction of the afferent arterioles and consequently reduce hyperfiltration-related renal damage. The beneficial effects of SGLT2 inhibitors on the heart and kidneys may halt the vicious cardiorenal cycle in patients with functional TR (9), which results in deterioration of renal function, hospitalization for heart failure, and cardiovascular mortality.
Accordingly, the Enavogliflozin Outcome Trial in Functional Tricuspid Regurgitation (EVENT) will test the hypothesis that, compared with placebo, therapy with the SGLT2 inhibitor enavogliflozin for 18 months would improve clinical and echocardiographic outcomes in HF patients with functional TR and preserved LVEF.
- Being tested
- Enavogliflozin, Placebo
- Medical subject headings
- Tricuspid Valve Insufficiency
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
EnavogliflozinDrug
Also called Envlo (brand name)
All study patients will receive enavogliflozin in addition to their prior medications. They will receive optimal medical treatment for their underlying disease such as hypertension, diabetes, arrhythmia and/or coronary artery disease.
PlaceboDrug
All study patients will receive placebo in addition to their prior medications. They will receive optimal medical treatment for their underlying disease such as hypertension, diabetes, arrhythmia and/or coronary artery disease.
| Study group | Role | What they receive |
|---|---|---|
| Enavogliflozin | Experimental | Enavogliflozin 0.3 mg qd for 18 months Receives: Drug: Enavogliflozin |
| Placebo | Placebo comparator | Placebo qd for 18 months Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Cardiovascular event
A composite of cardiovascular death, hospitalization for HF, or worsening of tricuspid regurgitation that occurs during follow-up
Measured: 18 months
Secondary outcomes (5)
All-cause death
All-cause death occurring during follow-up
Measured: 18 months
Cardiovascular clinical event
A cardiovascular composite (cardiovascular mortality or hospitalization for HF) occurring during follow-up
Measured: 18 months
Renal event
A renal composite (doubling of serum creatinine, decrease in the eGFR of 30% or more, renal replacement therapy, or renal death) occurring during follow-up
Measured: 18 months
Change of TR
Change of TR on echocardiography from baseline to 18 months follow-up
Measured: 18 months
Change of RV strain
Change of RV strain on echocardiography from baseline to 18 months follow-up
Measured: 18 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Sep 2023
- Study start25 Oct 2023
- Primary completionJun 2027 (estimated)
- Study completionAug 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Tricuspid RegurgitationStudies of the same condition, open and under way.
- More trials run by Asan Medical CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 541 participants (actual)
Sponsor and investigators
- Lead sponsor
- Asan Medical Center
- Sponsor type
- University, hospital or other
- Collaborators
- Daewoong Pharmaceutical Co. LTD.
- Responsible party
- Principal investigator, Duk-Hyun Kang, Asan Medical Center
- Investigators
- DUK HYUN KANG, MD, Principal investigator, Asan Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06027307
- Sponsor's protocol ID
- 2023-0070
- Acronym
- EVENT
- Status last verified
- Dec 2025
- First submitted
- 31 Aug 2023
- Last updated
- 29 Dec 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 29 Dec 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Multicenter, Randomized, Double-blind, Placebo-controlled Study to Assess the Effects of Enavogliflozin on Outcomes in Patients With Functional Tricuspid Regurgitation and Heart Failure With Preserved Left Ventricular Ejection Fraction
- ClinicalTrials.gov ID
- NCT06027307
- Acronym / sponsor ID
- EVENT / 2023-0070
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 541 participants (actual)
- Lead sponsor
- Asan Medical CenterUniversity, hospital or other
- Collaborators
- Daewoong Pharmaceutical Co. LTD.
- Study start
- 25 Oct 2023 (actual)
- Primary completion
- Jun 2027 (estimated)
- Study completion
- Aug 2027 (estimated)
- First posted
- 7 Sep 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The Enavogliflozin Outcome Trial in Functional Tricuspid Regurgitation (EVENT) was designed to examine the hypothesis that, compared with placebo, therapy with the SGLT2 inhibitor enavogliflozin would improve clinical and echocardiographic outcomes in heart failure (HF) patients with functional tricuspid regurgitation (TR) and preserved left ventricular ejection fraction (LVEF).
The primary objective of the EVENT study is to test the hypothesis that, compared with placebo, therapy with enavogliflozin for 18 months would improve a composite of cardiovascular events or worsening of TR on follow-up echocardiography in HF patients with functional TR and preserved LVEF. The secondary objective is to examine whether enavogliflozin is effective in reduction of renal events and tricuspid regurgitation, and to evaluate whether beneficial effects of enavogliflozin on primary outcomes are associated with reduction of all-cause mortality.
Detailed description
Functional tricuspid regurgitation (TR) develops due to functional and structural alterations related to heart failure (HF), mitral valve disease and atrial fibrillation. An increase in cardiac filling pressure due to left ventricular (LV) systolic or diastolic dysfunction leads to left atrial, right atrial (RA) and right ventricular (RV) remodeling, which causes tricuspid annular dilatation and TR. The development of significant functional TR causes RV dysfunction and further dilation of RV, which deteriorates TR. Functional TR may occur with HF with preserved or reduced ejection fraction (EF), and the prevalence of moderate-to-severe functional TR is around 19% in patients with HF. Regardless of LVEF or pulmonary artery pressure, presence of moderate or severe functional TR is associated with more symptoms, reduced cardiac output, and worse renal function. A vicious cycle of significant TR, RV volume overload, adverse remodeling of RA, RV, and tricuspid annulus, and consequent aggravation of TR is suggested as a pathophysiologic mechanism of the poor clinical outcomes of patients with TR, and the presence of moderate or severe functional TR is a strong independent determinant of mortality in patients with HF. Because functional TR has a strong prognostic impact and plays an important pathophysiologic role in patients with HF, functional TR is suggested as a therapeutic target in HF. However, there have been no proven medical therapies for TR and only loop diuretics are cautiously recommended for relief of congestive symptoms in patients with severe TR and signs of RV failure. In patients with functional TR associated with systolic dysfunction, medical therapy for HF with a reduced EF may diminish functional TR by improving LV systolic function. Otherwise, the morbidity and mortality of patients with functional TR remain high and a novel therapeutic agent is needed to improve clinical outcomes of HF patients with functional TR and a preserved LV ejection fraction.
Sodium-glucose co-transporter 2 (SGLT2) inhibitors induce urinary excretion of glucose and sodium by blocking the SGLT2 transporter in the proximal tubule (8). SGLT2 inhibitor-induced natriuresis lower cardiac preload and reduce pulmonary congestion and systemic edema. SGLT2 inhibitors also restore tubuloglomerular feedback and lower the intraglomerular pressure by vasoconstriction of the afferent arterioles and consequently reduce hyperfiltration-related renal damage. The beneficial effects of SGLT2 inhibitors on the heart and kidneys may halt the vicious cardiorenal cycle in patients with functional TR (9), which results in deterioration of renal function, hospitalization for heart failure, and cardiovascular mortality.
Accordingly, the Enavogliflozin Outcome Trial in Functional Tricuspid Regurgitation (EVENT) will test the hypothesis that, compared with placebo, therapy with the SGLT2 inhibitor enavogliflozin for 18 months would improve clinical and echocardiographic outcomes in HF patients with functional TR and preserved LVEF.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Enavogliflozin | Experimental | Drug: EnavogliflozinEnavogliflozin 0.3 mg qd for 18 months |
| Placebo | Placebo comparator | Drug: PlaceboPlacebo qd for 18 months |
Who may qualify
- Ages
- 20 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- Patients must agree to the study protocol and provide written informed consent
- Outpatients male or female between the age of 20 and 80
- Non-diabetic or type2 DM patients with HbA1c 6.5-10.5%
- HF with dyspnea of NYHA functional class II or III
- Presence of moderate or severe functional TR and preserved LVEF on echocardiography
Key exclusion criteria (22 listed)
- History of hypersensitivity or allergy to the study drugs, drugs of similar chemical classes, as well as known or suspected contraindications to the study drug
- Current use or prior use of a SGLT-2 inhibitor or combined SGLT-1 and 2 inhibitor
- Any evidence of structural tricuspid valve disease
- Any significant left-sided valve disease
- Left ventricular ejection fraction <50%
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| EnavogliflozinAlso: Envlo (brand name)All study patients will receive enavogliflozin in addition to their prior medications. They will receive optimal medical treatment for their underlying disease such as hypertension, diabetes, arrhythmia and/or coronary artery disease. | Drug | Enavogliflozin |
| PlaceboAll study patients will receive placebo in addition to their prior medications. They will receive optimal medical treatment for their underlying disease such as hypertension, diabetes, arrhythmia and/or coronary artery disease. | Drug | Placebo |
Primary outcome
Cardiovascular event
Time frame: 18 months
A composite of cardiovascular death, hospitalization for HF, or worsening of tricuspid regurgitation that occurs during follow-up
5 secondary outcomes
All-cause death
Time frame: 18 months
Cardiovascular clinical event
Time frame: 18 months
Renal event
Time frame: 18 months
Change of TR
Time frame: 18 months
Change of RV strain
Time frame: 18 months
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Dec 2025.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
DUK HYUN KANG, MD principal investigator
Asan Medical Center
5 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Enavogliflozin in people with Tricuspid Regurgitation and Heart Failure With Preserved Ejection Fraction, run by Asan Medical Center at 5 sites in South Korea.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 22 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 29 Dec 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 5 sites in South Korea. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Cardiovascular event (time frame: 18 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 29 Dec 2025.