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The Effects and Mechanism of SGLT2 Inhibitors in Stage B of Heart Failure With Hypertension

Primary Purpose

Heart Failure, Hypertension, Left Ventricle Remodeling

Status
Not yet recruiting
Phase
Phase 4
Locations
Study Type
Interventional
Intervention
Empagliflozin 10 MG
Placebo
Sponsored by
China National Center for Cardiovascular Diseases
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Heart Failure

Eligibility Criteria

40 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria: • Meeting all the following criteria: Aged 40 and above. Hypertensive patients currently taking at least one antihypertensive medication as recommended by guidelines, and blood pressure is within the target range (<140/90 mmHg). B-type natriuretic peptide (BNP) levels between 35-280 pg/mL or N- terminal pro-B-type natriuretic peptide (NT-pro BNP) levels between 125-1000 pg/mL in the past 6 months. Left atrial volume index measured by echocardiography exceeding 34 mL/m² in the past 6 months. Signing an informed consent form. Exclusion Criteria: • Exclusion criteria include any of the following conditions: History of diabetes. History of heart failure. History of coronary artery disease. Left ventricular systolic dysfunction, defined as LVEF < 50%. Systolic blood pressure < 100 mmHg. Persistent atrial fibrillation. Severe valvular heart disease. Severe obstructive disease of the left ventricular outflow tract, including aortic valve stenosis. Genitourinary tract infection. Chronic kidney disease or estimated Glomerular Filtration Rate (eGFR) < 45 ml/min/1.73m². Alanine aminotransferase or aspartate aminotransferase levels > 3 times the upper limit of normal. Contraindications to taking SGLT2 inhibitors. Currently taking SGLT2 inhibitors, SGLT-1/2 inhibitors, or other antihyperglycemic medications (including metformin, glucagon-like peptide-1 receptor agonists, etc.). Pregnancy or planning pregnant, or currently breastfeeding. Malignant tumors or other severe illnesses with a life expectancy of less than 3 years. History of alcohol abuse or substance abuse within the past year. Mental disorders or communication barriers, cognitive impairments, or other severe illnesses that may affect participation in the study. Participation in or currently participating in other clinical trials within the last 3 months. Known poor compliance with study follow-up or study drug. Any condition or contraindication that makes a person intolerant to magnetic resonance imaging (MRI) or contraindicates MRI examination, such as the presence of implanted intracranial aneurysm clips, cardiac pacemakers or defibrillators, insulin pumps, etc.

Sites / Locations

    Arms of the Study

    Arm 1

    Arm 2

    Arm Type

    Experimental

    Placebo Comparator

    Arm Label

    Empagliflozin

    Placebo

    Arm Description

    Outcomes

    Primary Outcome Measures

    Change of left atrial volume index
    The change of left atrial volume index after 6 months treatment

    Secondary Outcome Measures

    Change of cardiac structure and functional
    Left ventricular functional parameters, such as Left Ventricular Ejection Fraction (%), and the ratio of early diastolic mitral valve flow velocity to mitral annular motion velocity (E/e' ratio in cm/s), were assessed. Global Longitudinal Strain (%) was calculated as (length of the myocardium at end-systole - length of the myocardium at end-diastole) / length of the myocardium at end-diastole) × 100. Left ventricular structural parameters, including Left Ventricular Mass (g) and Body Surface Area (m²), were combined to calculate the Left Ventricular Mass Index in g/m². Left atrial functional parameters, including Left Atrial Ejection Fraction (%), Left Atrial Volume (mL), and Body Surface Area (m²), were assessed using transthoracic echocardiography. The Left Atrial Volume Index was reported in mL/m².
    Biomarkers
    Biomarker concentrations were measured as follows: NT-pro BNP in picograms per milliliter (pg/mL). Cardiac Troponin I in nanograms per milliliter (ng/mL). Cardiac Fibrosis Biomarkers, including Matrix Metalloproteinases (MMP-2, MMP-3, MMP-4) in picograms per milliliter (pg/mL) and soluble ST2 protein (sST-2) in nanograms per milliliter (ng/mL). Inflammation Biomarkers, including High-sensitivity C-reactive protein (hs-CRP) in milligrams per liter (mg/L) and Interleukin-6 (IL-6), Interleukin-1β (IL-1β), and Galectin-3 (Gal-3) in picograms per milliliter (pg/mL).
    Vascular Compliance
    24-hour ambulatory blood pressure monitoring.
    Estimated Glomerular Filtration Rate (eGFR)
    Change of eGFR

    Full Information

    First Posted
    September 14, 2023
    Last Updated
    September 20, 2023
    Sponsor
    China National Center for Cardiovascular Diseases
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    1. Study Identification

    Unique Protocol Identification Number
    NCT06055452
    Brief Title
    The Effects and Mechanism of SGLT2 Inhibitors in Stage B of Heart Failure With Hypertension
    Official Title
    The Effects and Mechanism of SGLT2 Inhibitors in Stage B of Heart Failure With Hypertension
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    September 2023
    Overall Recruitment Status
    Not yet recruiting
    Study Start Date
    November 1, 2023 (Anticipated)
    Primary Completion Date
    October 31, 2024 (Anticipated)
    Study Completion Date
    December 31, 2024 (Anticipated)

    3. Sponsor/Collaborators

    Responsible Party, by Official Title
    Sponsor
    Name of the Sponsor
    China National Center for Cardiovascular Diseases

    4. Oversight

    Studies a U.S. FDA-regulated Drug Product
    No
    Studies a U.S. FDA-regulated Device Product
    No

    5. Study Description

    Brief Summary
    This study is a multicenter randomized controlled trial designed to recruit individuals in the pre-heart failure stage who have hypertension without concurrent diabetes. Participants will be randomly allocated in a 1:1 ratio into the empagliflozin group (10 mg daily) or the placebo group, and they will undergo a follow-up period of 6 months. The primary endpoint for evaluation will be the left atrial volume index. The secondary endpoints will encompass cardiac structure and function parameters, as well as biomarkers obtained from blood samples. These biomarkers will include indicators of fibrosis, inflammation, cardiac function, and routine blood parameters. The overarching goal of the research is to comprehensively assess the impact of empagliflozin on the cardiac structure and function of pre-heart failure patients with hypertension while delving deeply into the mechanisms through which it exerts its effects.
    Detailed Description
    As a critical risk factor for heart failure, hypertension can induce left ventricular hypertrophy, decrease cardiac function, and ultimately lead to the development of heart failure. Sodium-glucose cotransporter 2 (SGLT2) inhibitors have been confirmed to reduce cardiovascular events and the risk of heart failure hospitalization in patients with diabetes and heart failure. They also exhibit beneficial effects, such as improving left ventricular structure, inhibiting myocardial fibrosis, anti-inflammatory properties, and promoting microcirculation improvement. However, whether SGLT2 inhibitors could provide myocardial protection in non-diabetic patients who have not yet developed heart failure remains uncertain. This study is a multicenter randomized controlled trial aiming to recruit pre-heart failure patients with hypertension without diabetes. These patients will be randomly allocated in a 1:1 ratio into the empagliflozin group (10 mg daily) or the placebo group, followed by a 6-month follow-up period. The study aims to investigate whether empagliflozin, under the precondition of well-controlled hypertension, could improve the cardiac structure and function of pre-heart failure patients, and explore the associated mechanisms based on the changes in biomarkers. The primary endpoint assessment will focus on the left atrial volume index, while the secondary endpoints will include parameters related to cardiac structure and function, as well as biomarkers detected from blood samples. These biomarkers encompass fibrosis indicators, inflammation markers, cardiac function indicators, and routine blood parameters. The objective of this study is to comprehensively evaluate the impact of empagliflozin on the cardiac structure and function of pre-heart failure patients with hypertension and delve into the underlying mechanisms of its function.

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    Heart Failure, Hypertension, Left Ventricle Remodeling, Left Atrial Dilatation

    7. Study Design

    Primary Purpose
    Treatment
    Study Phase
    Phase 4
    Interventional Study Model
    Parallel Assignment
    Masking
    ParticipantCare ProviderInvestigatorOutcomes Assessor
    Allocation
    Randomized
    Enrollment
    120 (Anticipated)

    8. Arms, Groups, and Interventions

    Arm Title
    Empagliflozin
    Arm Type
    Experimental
    Arm Title
    Placebo
    Arm Type
    Placebo Comparator
    Intervention Type
    Drug
    Intervention Name(s)
    Empagliflozin 10 MG
    Intervention Description
    Each participant in the empagliflozin treatment group takes a daily dose of 10mg.
    Intervention Type
    Drug
    Intervention Name(s)
    Placebo
    Intervention Description
    Each participant in the placebo group takes a daily dose of placebo 10mg.
    Primary Outcome Measure Information:
    Title
    Change of left atrial volume index
    Description
    The change of left atrial volume index after 6 months treatment
    Time Frame
    6 months
    Secondary Outcome Measure Information:
    Title
    Change of cardiac structure and functional
    Description
    Left ventricular functional parameters, such as Left Ventricular Ejection Fraction (%), and the ratio of early diastolic mitral valve flow velocity to mitral annular motion velocity (E/e' ratio in cm/s), were assessed. Global Longitudinal Strain (%) was calculated as (length of the myocardium at end-systole - length of the myocardium at end-diastole) / length of the myocardium at end-diastole) × 100. Left ventricular structural parameters, including Left Ventricular Mass (g) and Body Surface Area (m²), were combined to calculate the Left Ventricular Mass Index in g/m². Left atrial functional parameters, including Left Atrial Ejection Fraction (%), Left Atrial Volume (mL), and Body Surface Area (m²), were assessed using transthoracic echocardiography. The Left Atrial Volume Index was reported in mL/m².
    Time Frame
    6 months
    Title
    Biomarkers
    Description
    Biomarker concentrations were measured as follows: NT-pro BNP in picograms per milliliter (pg/mL). Cardiac Troponin I in nanograms per milliliter (ng/mL). Cardiac Fibrosis Biomarkers, including Matrix Metalloproteinases (MMP-2, MMP-3, MMP-4) in picograms per milliliter (pg/mL) and soluble ST2 protein (sST-2) in nanograms per milliliter (ng/mL). Inflammation Biomarkers, including High-sensitivity C-reactive protein (hs-CRP) in milligrams per liter (mg/L) and Interleukin-6 (IL-6), Interleukin-1β (IL-1β), and Galectin-3 (Gal-3) in picograms per milliliter (pg/mL).
    Time Frame
    6 months
    Title
    Vascular Compliance
    Description
    24-hour ambulatory blood pressure monitoring.
    Time Frame
    6 months
    Title
    Estimated Glomerular Filtration Rate (eGFR)
    Description
    Change of eGFR
    Time Frame
    6 months

    10. Eligibility

    Sex
    All
    Minimum Age & Unit of Time
    40 Years
    Accepts Healthy Volunteers
    No
    Eligibility Criteria
    Inclusion Criteria: • Meeting all the following criteria: Aged 40 and above. Hypertensive patients currently taking at least one antihypertensive medication as recommended by guidelines, and blood pressure is within the target range (<140/90 mmHg). B-type natriuretic peptide (BNP) levels between 35-280 pg/mL or N- terminal pro-B-type natriuretic peptide (NT-pro BNP) levels between 125-1000 pg/mL in the past 6 months. Left atrial volume index measured by echocardiography exceeding 34 mL/m² in the past 6 months. Signing an informed consent form. Exclusion Criteria: • Exclusion criteria include any of the following conditions: History of diabetes. History of heart failure. History of coronary artery disease. Left ventricular systolic dysfunction, defined as LVEF < 50%. Systolic blood pressure < 100 mmHg. Persistent atrial fibrillation. Severe valvular heart disease. Severe obstructive disease of the left ventricular outflow tract, including aortic valve stenosis. Genitourinary tract infection. Chronic kidney disease or estimated Glomerular Filtration Rate (eGFR) < 45 ml/min/1.73m². Alanine aminotransferase or aspartate aminotransferase levels > 3 times the upper limit of normal. Contraindications to taking SGLT2 inhibitors. Currently taking SGLT2 inhibitors, SGLT-1/2 inhibitors, or other antihyperglycemic medications (including metformin, glucagon-like peptide-1 receptor agonists, etc.). Pregnancy or planning pregnant, or currently breastfeeding. Malignant tumors or other severe illnesses with a life expectancy of less than 3 years. History of alcohol abuse or substance abuse within the past year. Mental disorders or communication barriers, cognitive impairments, or other severe illnesses that may affect participation in the study. Participation in or currently participating in other clinical trials within the last 3 months. Known poor compliance with study follow-up or study drug. Any condition or contraindication that makes a person intolerant to magnetic resonance imaging (MRI) or contraindicates MRI examination, such as the presence of implanted intracranial aneurysm clips, cardiac pacemakers or defibrillators, insulin pumps, etc.
    Central Contact Person:
    First Name & Middle Initial & Last Name or Official Title & Degree
    Xin Zheng, MD,PhD
    Phone
    +86 13681077247
    Email
    zhengxin@fuwai.com

    12. IPD Sharing Statement

    Plan to Share IPD
    No

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    The Effects and Mechanism of SGLT2 Inhibitors in Stage B of Heart Failure With Hypertension

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