Pharmacological Reduction of Right Ventricular Enlargement

• Status: Recruiting
• Trial end date: 2023-05-01
• Target enrollment: 0
• Participant gender: All

Summary

Functional tricuspid regurgitation (TR) has been regarded as a secondary phenomenon of heart failure (HF), mitral valve (MV) disease or atrial fibrillation. Regardless of left ventricular (LV) function or pulmonary artery pressure, presence of moderate or greater functional TR is associated with poor prognosis. When a patient develops functional TR, it causes RV dilation and tricuspid annular enlargement, which also lead to deterioration of TR. A vicious cycle of significant TR, RV volume overload, tricuspid annular dilation and consequent aggravation of TR is accepted as a main determinant of the poor clinical outcome of patients with TR. Therefore, therapies that induce reverse remodeling of the RV and consequently reduce TR, may improve clinical outcomes. However, there have been no proven medical therapies for TR. The investigators hypothesize that carvedilol or empagliflozin is effective on improving RV remodeling in patients with functional severe TR and try to examine this hypothesis in a multicenter, 2x2 factorial, and randomized comparison study using cardiac MRI.

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

Details

• Lead Sponsor: Asan Medical Center
• Collaborator: Chong Kun Dang Pharmaceutical Company
• Treatments: Carvedilol; Empagliflozin

Criteria

Inclusion Criteria:

• Patients must agree to the study protocol and provide written informed consent

• Outpatients ≥ 20 years of age, male or female

• Patients with severe functional tricuspid regurgitation

• TR whose vena contracta ≥0.7cm or central jet area > 10 square cm and which lasted > 6 months under medical treatment

• LV ejection fraction ≥ 40%

• Dyspnea of NYHA functional class II or III

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

• Significant left-sided valve disease

• Left ventricular ejection fraction <40%

• Marked bradycardia (<50 beats/min) or 2nd or 3rd degree AVB, sinus node dysfunction

• Severe pulmonary hypertension: TR Vmax >4m/s at screening (including Cor pulmonale)

• Medical history of hospitalization within 6 weeks

• Current acute decompensated heart failure or dyspnea of NYHA functional class IV

• Symptomatic hypotension and/or a SBP < 90 mmHg at screening Estimated GFR < 30 mL/min/1.73 square m

• History of ketoacidosis, Type 1 diabetes

• 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, severe peripheral artery disease or major CV surgery or PCI within 3 months

• History of severe pulmonary disease (asthma, COPD with bronchial hypersensitivity)

• Secondary hypertension such as pheochromocyotoma

• Acute pulmonary thromboembolism

• Variant angina, vocal cord edema, severe allergic rhinitis

• 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

• Contraindication for MRI

• Presence of pacemaker or ICD, implanted metallic objects, claustrophobia

• Severe beat-to-beat variation

• Galactose intolerance, Lapp lactose deficiency, glucose-galactose malabsorption

• 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