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

August 5, 2020 updated by: Yonsei University

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.

Study Overview

Detailed Description

Subjects : Patients with non-ischemic cardiomyopathy who need medical treatment Procedures : This is a prospective, randomized trial to compare cardiopulmonary motor tests, cardiac MRI including myocardial fibrosis parameters (ECV, etc.), and incidence of various heart failure-related cardiovascular events during the follow-up period between patients with ertugliflozin drug therapy and placebo drug. Patients meeting inclusion criteria without any exclusion criteria will be randomized 1:1 to ertugliflozin (5mg) or placebo therapy. Randomization will be stratified according to presence of diabetes mellitus, and the upper limit of randomized non-DM patients will be set as 36 patients (70%). The estimated enrollment period is 18 months (n=52) and all patients will be followed for 12 months after randomization. Random assignment is performed at random assignment visit (V1) through eCASE web system and following study procedures will be conducted according to the randomization. CMR, Cardiopulmonary exercise test, serum biomarkers, and clinical endpoints will be measured at 3,6,12 months.

Study Type

Interventional

Enrollment (Anticipated)

52

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

  • Name: Seok-Min Kang
  • Phone Number: 82-2-2228-8450
  • Email: smkang@yuhs.ac

Study Locations

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

19 years to 74 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Placebo Comparator: placebo
Placebo
Placebo group
Experimental: Ertugliflozin
Ertugliflozin 5mg
Fixed dose Ertugliflozin (5mg)

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
The ECV value change in CMR after Drug (Ertugliflozin or Placebo) administration
Time Frame: Baseline
The ECV value change in MRI from baseline to End of trial (48 weeks)
Baseline
The ECV value change in CMR after Drug (Ertugliflozin or Placebo) administration
Time Frame: 48 Weeks after drug administration
The ECV value change in MRI from baseline to End of trial (48 weeks)
48 Weeks after drug administration

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
CMR parameters : ECV (%)
Time Frame: baseline
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
CMR parameters : ECV (%)
Time Frame: 12 weeks after drug administration
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
CMR parameters : ECV (%)
Time Frame: 48 weeks after drug administration
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
CMR parameters : Native T1 (ms)
Time Frame: baseline
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
CMR parameters : Native T1 (ms)
Time Frame: 12 weeks after drug administration
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
CMR parameters : Native T1 (ms)
Time Frame: 48 weeks after drug administration
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
CMR parameters : left & right ventricular (LV & RV) mass index (g/m2)
Time Frame: Baseline
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
CMR parameters : left & right ventricular (LV & RV) mass index (g/m2)
Time Frame: 12 weeks after drug administration
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
CMR parameters : left & right ventricular (LV & RV) mass index (g/m2)
Time Frame: 48 weeks after drug administration
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
CMR parameters : LV & RV ejection fraction (%)
Time Frame: Baseline
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
CMR parameters : LV & RV ejection fraction (%)
Time Frame: 12 weeks after drug administration
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
CMR parameters : LV & RV ejection fraction (%)
Time Frame: 48 weeks after drug administration
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
CMR parameters : LV & RV end-systolic volume, LV & RV end-diastolic volume (ml)
Time Frame: Baseline
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
CMR parameters : LV & RV end-systolic volume, LV & RV end-diastolic volume (ml)
Time Frame: 12 weeks after drug administration
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
CMR parameters : LV & RV end-systolic volume, LV & RV end-diastolic volume (ml)
Time Frame: 48 weeks after drug administration
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
CMR parameters : cine-base cardiac strain (%)
Time Frame: Baseline
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
CMR parameters : cine-base cardiac strain (%)
Time Frame: 12 weeks after drug administration
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
CMR parameters : cine-base cardiac strain (%)
Time Frame: 48 weeks after drug administration
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
Biomarkers : NT-proBNP, hsTn, soluble ST2, galectin-3, IGFBP7
Time Frame: baseline
The change in degree of NT-proBNP, hsTn, soluble ST2, galectin-3, IGFBP7 after drug administration.
baseline
Biomarkers : NT-proBNP, hsTn, soluble ST2, galectin-3, IGFBP7
Time Frame: 12 weeks after drug administration
The change in degree of NT-proBNP, hsTn, soluble ST2, galectin-3, IGFBP7 after drug administration.
12 weeks after drug administration
Biomarkers : NT-proBNP, hsTn, soluble ST2, galectin-3, IGFBP7
Time Frame: 24 weeks after drug administration
The change in degree of NT-proBNP, hsTn, soluble ST2, galectin-3, IGFBP7 after drug administration.
24 weeks after drug administration
Biomarkers : NT-proBNP, hsTn, soluble ST2, galectin-3, IGFBP7
Time Frame: 48 weeks after drug administration
The change in degree of NT-proBNP, hsTn, soluble ST2, galectin-3, IGFBP7 after drug administration.
48 weeks after drug administration

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Anticipated)

August 1, 2020

Primary Completion (Anticipated)

December 1, 2021

Study Completion (Anticipated)

December 1, 2022

Study Registration Dates

First Submitted

July 20, 2020

First Submitted That Met QC Criteria

July 24, 2020

First Posted (Actual)

July 29, 2020

Study Record Updates

Last Update Posted (Actual)

August 7, 2020

Last Update Submitted That Met QC Criteria

August 5, 2020

Last Verified

August 1, 2020

More Information

Terms related to this study

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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