Enavogliflozin Outcome Trial in Functional Tricuspid Regurgitation

NCT06027307 | Active Not Recruiting Phase 3 DMC

• 1 other identifier: 2023-0070
• Study Type: interventional
• Target: 541
• Locations: 1 country
• Sites: 5

Brief 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 (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.

Conditions

Heart Failure With Preserved Ejection Fraction; Tricuspid Regurgitation

Outcome Measures

Primary Outcomes (1)

• Cardiovascular event

  A composite of cardiovascular death, hospitalization for HF, or worsening of tricuspid regurgitation that occurs during follow-up

  18 months

Secondary Outcomes (5)

• All-cause death

  18 months

• Cardiovascular clinical event

  18 months

• Renal event

  18 months

• Change of TR

  18 months

• Change of RV strain

  18 months

Study Arms (2)

Enavogliflozin

EXPERIMENTAL

Enavogliflozin 0.3 mg qd for 18 months

Drug: Enavogliflozin

Placebo

PLACEBO COMPARATOR

Placebo qd for 18 months

Drug: Placebo

Interventions

Enavogliflozin DRUG

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.

Also known as: Envlo (brand name)

Enavogliflozin

Placebo DRUG

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.

Placebo

Eligibility Criteria

• Age: 20 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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
• 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

Sponsors & Collaborators

• Asan Medical Center: lead
• Daewoong Pharmaceutical Co. LTD.: collaborator

Study Sites (5)

Inha University Hospital

Incheon, South Korea

Location

Asan Medical Center

Seoul, South Korea

Location

Samsung Medical Center

Seoul, South Korea

Location

Seoul National University Hospital

Seoul, South Korea

Location

Yonsei University Medical Center

Seoul, South Korea

Location

MeSH Terms

Conditions

Tricuspid Valve Insufficiency

Interventions

Enavogliflozin

Condition Hierarchy (Ancestors)

Heart Valve Diseases; Heart Diseases; Cardiovascular Diseases

Study Officials

• DUK HYUN KANG, MD

  Asan Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: August 31, 2023
• First Posted: September 7, 2023
• Study Start: October 25, 2023
• Primary Completion (Estimated): June 1, 2027
• Study Completion (Estimated): August 1, 2027
• Last Updated: December 29, 2025

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will not share

Locations

KR (5)