Validation of ERTugliflozin for Inhibiting Cardiac Fibrosis Using Cardiac MRI and Laboratory Parameters in Korean Heart Failure Patients With Nonischemic Cardiomyopathy(VERTICAL)

• Status: Not yet recruiting
• Trial end date: 2022-12-01
• Target enrollment: 0
• Participant gender: All

Summary

Based on recent studies demonstrating SGLT2 inhibitors' favorable effects on cardiovascular outcomes especially for heart failure, the investigators hypothesize that sodium-glucose co-transporter-2 (SGLT2) inhibitor, ertugliflozin, is effective on reducing cardiac fibrosis in patients with nonischemic cardiomyopathy so the investigators try to examine this hypothesis in a single-center, double-blind, randomized controlled study using cardiac magnetic resonance (CMR).

This study is a prospective, single-center, randomized, double-blind, two arm parallel group, placebo-controlled clinical trial involving patients with nonischemic cardiomyopathy. Patients meeting inclusion criteria without any exclusion criteria will be randomized 1:1 to ertugliflozin or placebo therapy, and cardiovascular functional assessment and clinical event follow-up will be undertaken.

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

Details

• Lead Sponsor: Yonsei University
• Treatments: Carvedilol; Ertugliflozin

Criteria

Inclusion Criteria:

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

• Outpatients ≥ 19 years, <75 years of age, male or female

• Non-diabetic or type 2 DM patients with HbA1c 7.0-10.5%

• Patients with nonischemic cardiomyopathy (LVEF ≤40%)

• Exclusion of ischemic origin cardiomyopathy using coronary angiography or CT angiography or SPECT scan (e.g. significant stenosis of proximal LAD or left main & myocardial infarction)

• Dyspnea of NYHA functional class II or III

• NT-proBNP ≥ 400 pg/ml (≥ 900 pg/ml if atrial fibrillation or atrial flutter)

• Titration of HF medications should be completed and patients must take a stable, optimized dose of a β-blocker and an ACE inhibitor (or ARB or ARNI if indicated) for at least 4 weeks prior to study entry

Exclusion Criteria:

• History of hypersensitivity or allergy to the study drug, drugs of similar chemical classes, or SGLT-2 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

• Known history of angioedema

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

• Medical history of hospitalization within 6 weeks

• Acute coronary syndrome, stroke, major CV surgery, PCI within 3 months

• Substantial myocardial ischemia requiring coronary revascularization therapy or a plan of coronary revascularization within 6 months

• A plan of heart transplantation or implantation of cardiac resynchronization therapy

• Symptomatic hypotension and/or a SBP < 95 mmHg at screening

• Estimated GFR < 30 mL/min/1.73m2

• History of ketoacidosis

• Symptomatic peripheral artery disease and history of lower limb amputation

• Evidence of hepatic disease as determined by any one of the following: AST or ALT values exceeding 3 x upper limit of normal (ULN) at screening visit (Visit 0), history of hepatic encephalopathy, history of esophageal varices, or history of portacaval shunt.

• History of severe pulmonary disease

• Significant mitral & aortic valve disease (e.g. moderate to severe, severe degree)

• 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