Heart Failure With Nonischemic Cardiomyopathy Clinical Trial
Official title:
Validation of ERTugliflozin for Inhibiting Cardiac Fibrosis Using Cardiac MRI and Laboratory Parameters in Korean Heart Failure Patients With Nonischemic Cardiomyopathy(VERTICAL)
| Verified date | August 2020 |
| Source | Yonsei University |
| Contact | Seok-Min Kang |
| Phone | 82-2-2228-8450 |
| smkang[@]yuhs.ac | |
| Is FDA regulated | No |
| Health authority | |
| Study type | Interventional |
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.
| Status | Not yet recruiting |
| Enrollment | 52 |
| Est. completion date | December 2022 |
| Est. primary completion date | December 2021 |
| Accepts healthy volunteers | No |
| Gender | All |
| Age group | 19 Years to 74 Years |
| Eligibility |
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 ß-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 |
| Country | Name | City | State |
|---|---|---|---|
| Korea, Republic of | Severance Hospiatal | Seoul |
| Lead Sponsor | Collaborator |
|---|---|
| Yonsei University |
Korea, Republic of,
| Type | Measure | Description | Time frame | Safety issue |
|---|---|---|---|---|
| Primary | The ECV value change in CMR after Drug (Ertugliflozin or Placebo) administration | The ECV value change in MRI from baseline to End of trial (48 weeks) | Baseline | |
| Primary | The ECV value change in CMR after Drug (Ertugliflozin or Placebo) administration | The ECV value change in MRI from baseline to End of trial (48 weeks) | 48 Weeks after drug administration | |
| Secondary | CMR parameters : ECV (%) | CMR parameters : the changes of myocardial fibrosis markers (ECV, Native T1), ventricular muscle mass marker (left & right ventricular (LV & RV) mass index), ventricular functional markers (LV & RV ejection fraction, cine-base cardiac strain), and ventricular remodeling markers (LV & RV end-systolic volume, LV & RV end-diastolic volume). These parameters represent myocardial fibrotic change, ventricular remodelling, systolic function. | baseline | |
| Secondary | CMR parameters : ECV (%) | CMR parameters : the changes of myocardial fibrosis markers (ECV, Native T1), ventricular muscle mass marker (left & right ventricular (LV & RV) mass index), ventricular functional markers (LV & RV ejection fraction, cine-base cardiac strain), and ventricular remodeling markers (LV & RV end-systolic volume, LV & RV end-diastolic volume). These parameters represent myocardial fibrotic change, ventricular remodelling, systolic function. | 12 weeks after drug administration | |
| Secondary | CMR parameters : ECV (%) | CMR parameters : the changes of myocardial fibrosis markers (ECV, Native T1), ventricular muscle mass marker (left & right ventricular (LV & RV) mass index), ventricular functional markers (LV & RV ejection fraction, cine-base cardiac strain), and ventricular remodeling markers (LV & RV end-systolic volume, LV & RV end-diastolic volume). These parameters represent myocardial fibrotic change, ventricular remodelling, systolic function. | 48 weeks after drug administration | |
| Secondary | CMR parameters : Native T1 (ms) | CMR parameters : the changes of myocardial fibrosis markers (ECV, Native T1), ventricular muscle mass marker (left & right ventricular (LV & RV) mass index), ventricular functional markers (LV & RV ejection fraction, cine-base cardiac strain), and ventricular remodeling markers (LV & RV end-systolic volume, LV & RV end-diastolic volume). These parameters represent myocardial fibrotic change, ventricular remodelling, systolic function. | baseline | |
| Secondary | CMR parameters : Native T1 (ms) | CMR parameters : the changes of myocardial fibrosis markers (ECV, Native T1), ventricular muscle mass marker (left & right ventricular (LV & RV) mass index), ventricular functional markers (LV & RV ejection fraction, cine-base cardiac strain), and ventricular remodeling markers (LV & RV end-systolic volume, LV & RV end-diastolic volume). These parameters represent myocardial fibrotic change, ventricular remodelling, systolic function. | 12 weeks after drug administration | |
| Secondary | CMR parameters : Native T1 (ms) | CMR parameters : the changes of myocardial fibrosis markers (ECV, Native T1), ventricular muscle mass marker (left & right ventricular (LV & RV) mass index), ventricular functional markers (LV & RV ejection fraction, cine-base cardiac strain), and ventricular remodeling markers (LV & RV end-systolic volume, LV & RV end-diastolic volume). These parameters represent myocardial fibrotic change, ventricular remodelling, systolic function. | 48 weeks after drug administration | |
| Secondary | CMR parameters : left & right ventricular (LV & RV) mass index (g/m2) | CMR parameters : the changes of myocardial fibrosis markers (ECV, Native T1), ventricular muscle mass marker (left & right ventricular (LV & RV) mass index), ventricular functional markers (LV & RV ejection fraction, cine-base cardiac strain), and ventricular remodeling markers (LV & RV end-systolic volume, LV & RV end-diastolic volume). These parameters represent myocardial fibrotic change, ventricular remodelling, systolic function. | Baseline | |
| Secondary | CMR parameters : left & right ventricular (LV & RV) mass index (g/m2) | CMR parameters : the changes of myocardial fibrosis markers (ECV, Native T1), ventricular muscle mass marker (left & right ventricular (LV & RV) mass index), ventricular functional markers (LV & RV ejection fraction, cine-base cardiac strain), and ventricular remodeling markers (LV & RV end-systolic volume, LV & RV end-diastolic volume). These parameters represent myocardial fibrotic change, ventricular remodelling, systolic function. | 12 weeks after drug administration | |
| Secondary | CMR parameters : left & right ventricular (LV & RV) mass index (g/m2) | CMR parameters : the changes of myocardial fibrosis markers (ECV, Native T1), ventricular muscle mass marker (left & right ventricular (LV & RV) mass index), ventricular functional markers (LV & RV ejection fraction, cine-base cardiac strain), and ventricular remodeling markers (LV & RV end-systolic volume, LV & RV end-diastolic volume). These parameters represent myocardial fibrotic change, ventricular remodelling, systolic function. | 48 weeks after drug administration | |
| Secondary | CMR parameters : LV & RV ejection fraction (%) | CMR parameters : the changes of myocardial fibrosis markers (ECV, Native T1), ventricular muscle mass marker (left & right ventricular (LV & RV) mass index), ventricular functional markers (LV & RV ejection fraction, cine-base cardiac strain), and ventricular remodeling markers (LV & RV end-systolic volume, LV & RV end-diastolic volume). These parameters represent myocardial fibrotic change, ventricular remodelling, systolic function. | Baseline | |
| Secondary | CMR parameters : LV & RV ejection fraction (%) | CMR parameters : the changes of myocardial fibrosis markers (ECV, Native T1), ventricular muscle mass marker (left & right ventricular (LV & RV) mass index), ventricular functional markers (LV & RV ejection fraction, cine-base cardiac strain), and ventricular remodeling markers (LV & RV end-systolic volume, LV & RV end-diastolic volume). These parameters represent myocardial fibrotic change, ventricular remodelling, systolic function. | 12 weeks after drug administration | |
| Secondary | CMR parameters : LV & RV ejection fraction (%) | CMR parameters : the changes of myocardial fibrosis markers (ECV, Native T1), ventricular muscle mass marker (left & right ventricular (LV & RV) mass index), ventricular functional markers (LV & RV ejection fraction, cine-base cardiac strain), and ventricular remodeling markers (LV & RV end-systolic volume, LV & RV end-diastolic volume). These parameters represent myocardial fibrotic change, ventricular remodelling, systolic function. | 48 weeks after drug administration | |
| Secondary | CMR parameters : LV & RV end-systolic volume, LV & RV end-diastolic volume (ml) | CMR parameters : the changes of myocardial fibrosis markers (ECV, Native T1), ventricular muscle mass marker (left & right ventricular (LV & RV) mass index), ventricular functional markers (LV & RV ejection fraction, cine-base cardiac strain), and ventricular remodeling markers (LV & RV end-systolic volume, LV & RV end-diastolic volume). These parameters represent myocardial fibrotic change, ventricular remodelling, systolic function. | Baseline | |
| Secondary | CMR parameters : LV & RV end-systolic volume, LV & RV end-diastolic volume (ml) | CMR parameters : the changes of myocardial fibrosis markers (ECV, Native T1), ventricular muscle mass marker (left & right ventricular (LV & RV) mass index), ventricular functional markers (LV & RV ejection fraction, cine-base cardiac strain), and ventricular remodeling markers (LV & RV end-systolic volume, LV & RV end-diastolic volume). These parameters represent myocardial fibrotic change, ventricular remodelling, systolic function. | 12 weeks after drug administration | |
| Secondary | CMR parameters : LV & RV end-systolic volume, LV & RV end-diastolic volume (ml) | CMR parameters : the changes of myocardial fibrosis markers (ECV, Native T1), ventricular muscle mass marker (left & right ventricular (LV & RV) mass index), ventricular functional markers (LV & RV ejection fraction, cine-base cardiac strain), and ventricular remodeling markers (LV & RV end-systolic volume, LV & RV end-diastolic volume). These parameters represent myocardial fibrotic change, ventricular remodelling, systolic function. | 48 weeks after drug administration | |
| Secondary | CMR parameters : cine-base cardiac strain (%) | CMR parameters : the changes of myocardial fibrosis markers (ECV, Native T1), ventricular muscle mass marker (left & right ventricular (LV & RV) mass index), ventricular functional markers (LV & RV ejection fraction, cine-base cardiac strain), and ventricular remodeling markers (LV & RV end-systolic volume, LV & RV end-diastolic volume). These parameters represent myocardial fibrotic change, ventricular remodelling, systolic function. | Baseline | |
| Secondary | CMR parameters : cine-base cardiac strain (%) | CMR parameters : the changes of myocardial fibrosis markers (ECV, Native T1), ventricular muscle mass marker (left & right ventricular (LV & RV) mass index), ventricular functional markers (LV & RV ejection fraction, cine-base cardiac strain), and ventricular remodeling markers (LV & RV end-systolic volume, LV & RV end-diastolic volume). These parameters represent myocardial fibrotic change, ventricular remodelling, systolic function. | 12 weeks after drug administration | |
| Secondary | CMR parameters : cine-base cardiac strain (%) | CMR parameters : the changes of myocardial fibrosis markers (ECV, Native T1), ventricular muscle mass marker (left & right ventricular (LV & RV) mass index), ventricular functional markers (LV & RV ejection fraction, cine-base cardiac strain), and ventricular remodeling markers (LV & RV end-systolic volume, LV & RV end-diastolic volume). These parameters represent myocardial fibrotic change, ventricular remodelling, systolic function. | 48 weeks after drug administration | |
| Secondary | Biomarkers : NT-proBNP, hsTn, soluble ST2, galectin-3, IGFBP7 | The change in degree of NT-proBNP, hsTn, soluble ST2, galectin-3, IGFBP7 after drug administration. | baseline | |
| Secondary | Biomarkers : NT-proBNP, hsTn, soluble ST2, galectin-3, IGFBP7 | The change in degree of NT-proBNP, hsTn, soluble ST2, galectin-3, IGFBP7 after drug administration. | 12 weeks after drug administration | |
| Secondary | Biomarkers : NT-proBNP, hsTn, soluble ST2, galectin-3, IGFBP7 | The change in degree of NT-proBNP, hsTn, soluble ST2, galectin-3, IGFBP7 after drug administration. | 24 weeks after drug administration | |
| Secondary | Biomarkers : NT-proBNP, hsTn, soluble ST2, galectin-3, IGFBP7 | The change in degree of NT-proBNP, hsTn, soluble ST2, galectin-3, IGFBP7 after drug administration. | 48 weeks after drug administration |