Enavogliflozin Outcome Trial in Functional Tricuspid Regurgitation

• Status: Recruiting
• Trial end date: 2027-10-01
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 3
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Asan Medical Center
• Collaborator: Daewoong Pharmaceutical Co. LTD.

Criteria

Inclusion Criteria:

• 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

Exclusion Criteria:

• 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

• 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