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

NCT04707352 | Completed Phase 3

• 1 other identifier: ESR-20-20594 - MODA study
• Study Type: interventional
• Target: 162
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Heart Failure

Outcome Measures

Primary Outcomes (1)

• Change in LAVI from baseline to 6 months.

  Up to 6 months

Secondary Outcomes (8)

• Change in LAVI-min (minimal left atrial volume index)

  Up to 6 months

• Change in LAEF (left atrial ejection)

  Up to 6 months

• Change in LAFI (left atrial functional index)

  Up to 6 months

• Change in LA reservoir, conduit and pump volumes, emptying fractions and strain rates

  Up to 6 months

• Change in Left ventricular end-systolic volume index (LVESVi)

  Up to 6 months

Study Arms (1)

Dapagliflozin

EXPERIMENTAL

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

Interventions

Dapagliflozin DRUG

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).

Dapagliflozin

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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).

You may not qualify if:

• 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
• Implantation of a cardiac resynchronization therapy (CRT) within 12 weeks prior to enrolment or intent to implant a CRT device
• 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)

Sponsors & Collaborators

• Fundacion para la Formacion e Investigacion Sanitarias de la Region de Murcia: lead
• Spanish Society of Cardiology: collaborator

Study Sites (1)

Hospital Clinico Universitario Virgen de la Arrixaca

Murcia, 30003, Spain

Location

Related Publications (1)

• Pascual-Figal DA, Zamorano JL, Domingo M, Morillas H, Nunez J, Cobo Marcos M, Riquelme-Perez A, Teis A, Santas E, Caro-Martinez C, Pinilla JM, Rodriguez-Palomares JF, Dobarro D, Restrepo-Cordoba MA, Gonzalez-Juanatey JR, Bayes Genis A; DAPA-MODA Study Investigators. Impact of dapagliflozin on cardiac remodelling in patients with chronic heart failure: The DAPA-MODA study. Eur J Heart Fail. 2023 Aug;25(8):1352-1360. doi: 10.1002/ejhf.2884. Epub 2023 Jun 7.

  PMID: 37211950 DERIVED

MeSH Terms

Conditions

Heart Failure

Interventions

dapagliflozin

Condition Hierarchy (Ancestors)

Heart Diseases; Cardiovascular Diseases

Study Officials

• Domingo Pascual Figal

  Hospital Universitario Virgen de la Arrixaca

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Interventional, open-label and single-arm

Study Record Dates

• First Submitted: January 11, 2021
• First Posted: January 13, 2021
• Study Start: February 8, 2021
• Primary Completion: March 26, 2023
• Study Completion: March 26, 2023
• Last Updated: July 12, 2023

Record last verified: 2023-02

Locations

ES (1)