Impact on Atrial Remodeling of Dapaglifozin in Patients With Heart Failure . (MODA)

July 11, 2023 updated by: Fundacion para la Formacion e Investigacion Sanitarias de la Region de Murcia

Dapagliflozin reduces the risk of de novo heart failure (HF) in diabetics and, recently, it has shown to improve the prognosis of patients with HF and reduced left ventricular ejection fraction (HFrEF), by preventing HF decompensations and cardiovascular death. The benefit showed by dapagliflozin in HFrEF was irrespective of diabetes status and glycemic control, which raises the question of which mechanisms are underlying apart from SGLT2 inhibition. In addition, the impact of dapagliflozin on cardiac remodeling parameters, as assessed by echocardiography and biomarkers, is not well established. In particular, left atrial (LA) remodeling represents a relevant prognostic marker, which has received a greater attention in the last years in the context of new imaging tools.

The purpose of this study is to assess the effect of dapagliflozin therapy over a period of 6 months in LA remodeling parameters, including geometry and function, as well as complementary biomarkers in patients with chronic HF regardless left ventricular ejection fraction (LVEF). This protocol will allow for evaluation of improved understanding of the interplay between dapagliflozin and LA function , biomarkers, remodeling and outcomes, and will carefully assess such relationships within important cohorts of subjects, such as those with reduced and preserved LVEF.

This protocol will also generate a biorepository of well-handled and carefully considered biomarkers, which will allow a better understanding of dapagliflozin mechanism of action.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

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

The reduction of death and HF related events observed with dapagliflozin make necessary to clarify the mechanisms underlying these clinical benefits. Currently, dapagliflozin is indicated in patients with diabetes irrespective of the presence of HF. The initiation in patients with HF represents an opportunity to elucidate the effect of dapagliflozin on cardiac remodeling in this population. Therefore, we propose a study that aims to assess the effects of dapagliflozin in echocardiographic parameters of cardiac remodeling, with special interest in LA geometry and function, as well as in biomarkers reflecting expanded pathophysiological pathways. LA volume has shown to identify the progression of HF irrespective of LVEF and, therefore, it represents a meaningful measure of the cardiac impact of dapagliflozin in the entire spectrum of chronic HF.

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 (Actual)

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.
162

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 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

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: Domingo A Pascual figal, MD
  • Phone Number: 968381027
  • Email: dpascual@um.es

Study Locations

  • Spain
      • Murcia, Spain, 30003
        • Hospital Clinico Universitario Virgen de la Arrixaca

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

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Age > 18 years

    • Prior diagnosis of HF, with at least one hospitalization for HF at any time.
  • NYHA class I-IV.
  • LVEF available (echocardiogram or cardiac MRI) within the last 12 months prior to enrolment.
  • Treatment according with contemporary guidelines recommendations and with stable doses of oral loop diuretics for at least 4 weeks
  • NT-proBNP >600 pg/ml at screening (≥400 pg/ml if hospitalized for HF within the previous 12 months; ≥900 pg/ml If concomitant AF at
  • Screening irrespective of time to last HF hospitalization).

Exclusion Criteria:

  • Dapagliflozin or other SGLT2i at any time in prior 6 months.
  • Type 1 diabetes mellitus (T1D)
  • Estimated glomerular filtration rate < 30 ml/min/1.73 m2 as measured by the simplified Modification of Diet in Renal Disease (MDRD) formula at screening.
  • Symptomatic hypotension or systolic blood pressure (SBP) <95 mmHg on 2 consecutive measurements at screening.
  • Uncontrolled hypertension, defined as SBP >160 mmHg.
  • Current acute decompensated HF or hospitalization due to decompensated HF within 4 weeks prior to enrolment
  • The use of outpatient or inpatient i.v. diuretic therapy within 4 weeks prior to baseline.
  • Subjects who are currently receiving or have received inotropic agents within 12 weeks prior to baseline.
  • Myocardial infarction, unstable angina, stroke or transient ischemic attack within 12 weeks prior to enrolment
  • Coronary revascularization (percutaneous coronary intervention or coronary artery bypass grafting or valvular repair/replacement within 12 weeks prior to enrolment or planned to undergo any of these operations after inclusion
  • Implantation of a cardiac resynchronization therapy (CRT) within 12 weeks prior to enrolment or intent to implant a CRT device
  • Previous cardiac transplantation or implantation of a ventricular assistance device (VAD) or similar device, or implantation expected after inclusion
  • HF due to restrictive cardiomyopathy, active myocarditis, constrictive pericarditis, hypertrophic (obstructive) cardiomyopathy or uncorrected primary valvular disease
  • Symptomatic bradycardia or second or third degree heart block without a pacemaker
  • History of allergic reactions or intolerance to dapagliflozin, or other iSGLT2, or any other compound
  • History of malignancy of any organ system (other than localized basal cell carcinoma of the skin), treated or untreated, within one year.
  • Hepatic impairment aspartate transaminase [AST] or alanine transaminase [ALT] >3x the upper limit of normal [ULN]; or total bilirubin >2x ULN at time of screening)
  • Women of child-bearing potential (ie, those who are not chemically or surgically sterilised or who are not post-menopausal) who are not willing to use a medically accepted method of contraception that is considered reliable in the judgment of the investigator or women who have a positive pregnancy test at enrollment or randomization or women who are breast-feeding
  • Participation in another clinical trial during the last month prior to enrolment
  • Inability of the patient, in the opinion of the investigator, to understand and/or comply with study medications, procedures and/or follow-up or any conditions that, in the opinion of the investigator, may render the patient unable to complete the study
  • Any concomitant disease limiting life expectancy in the following year (other than heart failure)
  • No possibility to give informed consent.

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: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

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: Dapagliflozin
The baseline procedures will be performed on the same day of screening or within the next five working days. All the baseline procedures will be performed on the same day. The baseline procedures include biobank, clinical assessment and echocardiogram, on the same day. In the following 24 hours, the patient will initiate Dapagliflozin at the recommended dose of 10 mg daily during 6 months. Temporary discontinuation may be considered at investigator criteria as in cases of symptomatic hypotension or acute declines in renal function and after discarding other potential causes.
Drug: Dapagliflozin
All eligible subjects will receive Dapagliflozin 10 mg each day. The study treatment will be provided for the duration of the trial from baseline (Day 1) through last visit (Day 180).

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
Time Frame
Change in LAVI from baseline to 6 months.
Time Frame: Up to 6 months
Up to 6 months

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
Time Frame
Change in LAVI-min (minimal left atrial volume index)
Time Frame: Up to 6 months
Up to 6 months
Change in LAEF (left atrial ejection)
Time Frame: Up to 6 months
Up to 6 months
Change in LAFI (left atrial functional index)
Time Frame: Up to 6 months
Up to 6 months
Change in LA reservoir, conduit and pump volumes, emptying fractions and strain rates
Time Frame: Up to 6 months
Up to 6 months
Change in Left ventricular end-systolic volume index (LVESVi)
Time Frame: Up to 6 months
Up to 6 months
Change in left ventricular mass index (LVMI) Change in ventricular end-diastolic volume index (LVEDVi)
Time Frame: Up to 6 months
Up to 6 months
Change in global longitudinal strain (GLS)
Time Frame: Up to 6 months
Up to 6 months
Change in tricuspid annular plane systolic
Time Frame: Up to 6 months
Up to 6 months

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.
Fundacion para la Formacion e Investigacion Sanitarias de la Region de Murcia

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
Spanish Society of Cardiology

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: Domingo Pascual Figal, Hospital Clinico Universitario Virgen de la Arrixaca

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 (Actual)

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.
February 8, 2021

Primary Completion (Actual)

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.
March 26, 2023

Study Completion (Actual)

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.
March 26, 2023

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).
January 11, 2021

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.
January 11, 2021

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.
January 13, 2021

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.
July 12, 2023

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.
July 11, 2023

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.
February 1, 2023

More Information

Terms related to this study

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.
  • ESR-20-20594 - MODA study

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.

Clinical Trials on Heart Failure

Clinical Trials on Dapagliflozin

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

Cookie Settings

We use cookies to ensure that we give you the best experience on our website. For more details carefully read our Privacy and Cookies Policy. ...>>>You can change your preferences or withdraw your consent at any time by deleting the cookies from your website or computer as described in the policy. Please accept it and choose your preferences by ticking the corresponding boxes in the "Manage Settings" section below. Please carefully read our Terms of Service before you proceed with using any part of this website.
«Manage Settings