The Efficacy of Enavogliflozin in Heart Failure With Preserved Ejection Fraction (ENRICH-PEF)

April 5, 2024 updated by: Jeong Hoon Yang, Samsung Medical Center

The Efficacy of Enavogliflozin on Exercise Performance and Diastolic Function in Heart Failure With Preserved Ejection Fraction: A Randomized Controlled Trial

The aim of prospective, open label, single center, randomized controlled trial is to investigate the efficacy of enavogliflozin on exercise performance, diastolic dysfunction, and quality of life in patients with heart failure with preserved ejection fraction (HFpEF).

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Not yet recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

HFpEF is a clinically heterogenous syndrome and has unique characteristics that differ from the other entities of heart failure. Cardiovascular and non-cardiovascular comorbidities are known to contribute to the pathogenesis of HFpEF, and consequently, the importance of HFpEF is increasingly emphasized as the population ages. In fact, HFpEF occurs in approximately 5% of the general population aged over 60 years and account for half of hospitalization for heart failure. Notwithstanding, no medication has been found to be effective for HFpEF. Only recently, Sodium glucose cotransporter 2 (SGLT2) inhibitors was proven effective in patients with HFpEF in two landmark trials, EMPEROR-Preserved and DELIVER trials. In both trials, SGLT2 inhibitor was consistently associated with reduced risk of composite outcome of cardiovascular death and hospitalization for heart failure. In this regard, 2023 focused update of the 2021 European Society of Cardiology (ESC) guidelines for heart failure recommends SGLT2 inhibitor as class 1A recommendation in patients with HFpEF.

Despite the solid evidence about the clinical benefit of SGLT2 inhibitor in patients with HFpEF, little is known about the mechanisms responsible for the beneficial cardiac effects of SGLT2 inhibitor. Patients with HFpEF are known to have impaired exercise and functional capacity, which lead to declined quality of life and debilitating symptoms. Along with unclear mechanisms responsible for the beneficial cardiac effect of SGLT2 inhibitor, the impacts of SGLT2 inhibitor on exercise and functional capacity in patients with HFpEF have also not been clearly evaluated. Therefore, this trial aim to evaluate the impact of SGLT2 inhibitor on exercise performance, diastolic function, and quality of life in patients with HFpEF using newly developed SGLT2 inhibitor, Enavogliflozin.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Estimated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
154

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 4

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

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.
  • Name: Jeong Hoon Yang, MD, PhD
  • Phone Number: 82-2-3410-6475
  • Email: jhysmc@gmail.com

Study Contact Backup

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

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

1. Inclusion Criteria:

1) Age ≥19 2) New York Heart Association (NYHA) II-III dyspnea 3) Diagnosis of HFpEF (Exams conducted within 6 months from screening) [must satisfy all (1), (2), and (3)]

  1. Left ventricular ejection fraction (LVEF) ≥50%
  2. NT-proBNP ≥220 pg/mL or BNP ≥80 pg/mL, if in sinus rhythm NT-proBNP ≥660 pg/mL or BNP ≥240 pg/mL, if in atrial fibrillation

  3. Satisfying either noninvasive or invasive criteria I. Noninvasive: Echocardiography with at least one of the following criteria

    • LAVI ≥34 ml/m2
    • Lateral E/e' ≥9
    • LVMI ≥115 g/m2 if male or ≥95 g/m2 if female

    • LV wall thickness ≥12mm II. Invasive: LVEDP ≥16mmHg or pulmonary capillary wedge pressure(PCWP) ≥15mmHg 4) Stable/chronic ambulatory patients without hospitalization within the last 30 days due to heart failure decompensation episode 5) Patients taking heart failure medication without change for at least 3 weeks before screening

      2. Exclusion Criteria:

      1. Unwillingness or inability to comply with the procedures described in this protocol
      2. The ability to walk is, in the investigator's opinion, clearly limited by joint disease or other locomotor problems or lung diseases rather than by cardiorespiratory fitness
      3. NYHA IV dyspnea
      4. Type 1 diabetes mellitus
      5. Estimated glomerular filtration rate (eGFR) <60 ml/min/1.73m2 (Chronic Kidney Disease Epidemiology Collaboration [CKD-EPI] formula)
      6. Anemia (Hb <7g/dL)
      7. Severe hepatic impairment (Child-Pugh class C)
      8. Acute myocardial infarction or unstable angina within 30 days before inclusion or planned coronary revascularization at the time of inclusion
      9. Significant left-sided valvular heart disease (moderate to severe stenosis and severe regurgitation)
      10. Heart failure due to any of the following: infiltrative cardiomyopathy (amyloidosis, sarcoidosis), active myocarditis, constrictive pericarditis, hypertrophic cardiomyopathy
      11. Symptomatic hypotension (systolic blood pressure <90mmHg)
      12. Severe chronic obstructive pulmonary disease (postbronchodilator forced expiratory volume in 1 second (FEV1)/forced vital capacity(FVC) <70% and FEV1 <50%)
      13. Treated with sodium-glucose cotransporter-2 inhibitors (SGLT2i) within 30 days before inclusion
      14. History of diabetic ketoacidosis while in treatment with SGLT2i
      15. Recurrent genitourinary tract infections
      16. History of Hypersensitivity reaction to SGLT2i
      17. Non-cardiac co-morbid conditions are present with life expectancy <2 year or that may result in protocol non-compliance (per site investigator's medical judgment)
      18. Female patients who are currently or planning to become pregnant
      19. Female patients who are lactating
      20. Patients participating in other clinical trials

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: Single

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: SGLT2 inhibitor group
SGLT2 inhibitor group will receive Enavogliflozin (0.3mg oral tablet once daily).
Drug: SGLT2 inhibitor
Enavogliflozin (0.3mg oral tablet once daily) will be administrated.
Other Names:
  • SGLT2 inhibitor: Enavogliflozin (Brand names: Envlo tab)
No Intervention: Control group
Control group will not receive any SGLT2 inhibitors during the study period.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Change in peak oxygen consumption (VO2)
Time Frame: Week 24
Change in peak oxygen consumption (VO2) from baseline to week 24
Week 24

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Change in minute ventilation to carbon dioxide output ratio (VE/VCO2 slope)
Time Frame: Week 24
Change in minute ventilation to carbon dioxide output ratio (VE/VCO2 slope) from baseline to week 24
Week 24
Change in LV wall thickness before and after maximal exercise
Time Frame: Week 24
Change in LV wall thickness before and after maximal exercise from baseline to week 24
Week 24
Change in LV global longitudinal strain before and after maximal exercise
Time Frame: Week 24
Change in LV global longitudinal strain before and after maximal exercise from baseline to week 24
Week 24
Change in LA strain before and after maximal exercise
Time Frame: Week 24
Change in LA strain before and after maximal exercise from baseline to week 24
Week 24
Change in chronotropic response reserve assessed by change in heart rate from rest to peak exercise
Time Frame: Week 24
Change in chronotropic response reserve assessed by change in heart rate from rest to peak exercise from baseline to week 24
Week 24
Change in serum iron
Time Frame: Week 24
Change in serum iron from baseline to week 24
Week 24
Change in ferritin
Time Frame: Week 24
Change in ferritin from baseline to week 24
Week 24
Change in total iron binding capacity
Time Frame: Week 24
Change in total iron binding capacity from baseline to week 24
Week 24
Change in hemoglobin
Time Frame: Week 24
Change in hemoglobin from baseline to week 24
Week 24
All-cause death
Time Frame: Week 24
All-cause death
Week 24
Hospitalization for heart failure
Time Frame: Week 24

Hospitalization for heart failure should include all of the following criteria:

  1. Hospitalization with primary diagnosis of heart failure
  2. Duration of hospitalization of at least 12 hours
  3. New or worsening symptoms of heart failure
  4. Objective evidence of new or worsening heart failure on physical examination or laboratory findings
  5. Initiation or intensification of heart failure treatment.
Week 24
Change in Left atrial volume index (LAVI) before and after maximal exercise
Time Frame: Week 24
Change in LAVI before and after maximal exercise from baseline to week 24
Week 24
Change in Lateral Early diastolic transmitral filling velocity over early diastolic relaxation velocity at mitral annulus (E/e') before and after maximal exercise
Time Frame: Week 24
Change in Lateral E/e' before and after maximal exercise from baseline to week 24
Week 24
Change in Left ventricular mass index (LVMI) before and after maximal exercise
Time Frame: Week 24
Change in LVMI before and after maximal exercise from baseline to week 24
Week 24
Change in right ventricular (RV) free wall strain before and after maximal exercise
Time Frame: Week 24
Change in RV free wall strain before and after maximal exercise from baseline to week 24
Week 24
Change in health-related quality of life assessed by the Kansas City Cardiomyopathy Questionnaire Clinical Summary Score (KCCQ-CS)
Time Frame: Week 24

Change in health-related quality of life assessed by the Kansas City Cardiomyopathy Questionnaire Clinical Summary Score (KCCQ-CS) from baseline to week 24

Score ranges from 0 to 100 and higher value represents better quality of life.
Week 24
Change in N-Terminal pro-B-type Natriuretic Peptide (NT-proBNP) level
Time Frame: Week 24
Change in NT-proBNP level from baseline to week 24
Week 24

Collaborators and Investigators

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

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Samsung Medical Center

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Jeong Hoon Yang, MD, PhD, Samsung Medical Center

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 (Estimated)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
May 1, 2024

Primary Completion (Estimated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
December 31, 2025

Study Completion (Estimated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
June 30, 2026

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
April 1, 2024

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
April 1, 2024

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
April 5, 2024

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
April 8, 2024

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
April 5, 2024

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
April 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • SMC2024-01-089-003

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

After publication of first manuscript and trial results, de-identified data will be shared upon reasonable request and with permission from the principal investigator.

IPD Sharing Time Frame

After publication of first manuscript and trial results, de-identified data will be shared upon reasonable request and with permission from the principal investigator.

IPD Sharing Access Criteria

After publication of first manuscript and trial results, de-identified data will be shared upon reasonable request and with permission from the principal investigator.

IPD Sharing Supporting Information Type

  • STUDY_PROTOCOL
  • SAP
  • CSR

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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