Cardiometabolic Effects of Dapagliflozin in Heart Failure With Reduced or Mildly Reduced Ejection Fraction

NCT05420285 | Unknown Phase 2

• 2 other identifiers: APHP2101662021-000481-14
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

Brief Summary

Gliflozins have demonstrated a beneficial effect in terms of incident heart failure and related events in patients with or without diabetes. The clinical trial ICARD is an exploratory study that aims to evaluate the cardiometabolic mechanistic effects on the myocardium of dapagliflozin in heart failure with reduced ejection fraction. Deep phenotyping of cardiac and vascular function will be performed using MRI. Myocardial tissue characterization will be based on MRI and FDG-PET for glucose metabolism assessment. Liver steatosis and fibrosis will simultaneously be assessed.

Conditions

Heart Failure; Reduced Ejection Fraction

Keywords

heart failure; HFrEF; myocardial function; fibrosis; metabolism

Outcome Measures

Primary Outcomes (1)

• To evaluate changes in left ventricular (LV) extracellular mass index (ECMi) measured by MRI, induced by once-daily dapagliflozin 10mg during 6 months in patients with heart failure and reduced ejection fraction

  MRI measurement of changes in left ventricular extracellular mass index (ECMI) after a 6-month once-daily dapagliflozin 10 mg regimen

  6 months

Secondary Outcomes (29)

• To evaluate myocardial morphology

  6 months

• To evaluate myocardial morphology

  6 months

• Left ventricular ejection fraction as a biomarker of myocardial function

  6 months

• Right ventricular ejection fraction as a biomarker of myocardial function

  6 months

• Left atrial ejection fraction as a biomarker of myocardial function

  6 months

Study Arms (1)

Dapagliflozin

EXPERIMENTAL

Dapagliflozin is taken orally, once daily at the dosage of 10 mg during 6 months.

Drug: Dapagliflozin

Interventions

Dapagliflozin DRUG

Dapagliflozin (Forxiga) is a very potent selective and reversible inhibitor of SGLT2.

Also known as: Forxiga

Dapagliflozin

Eligibility Criteria

• Age: 18 Years - 100 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥ 18 years
• NYHA functional class II-IV.
• Previous hospitalization for heart failure anytime or NT-proBNP \>125 pg/ml in the previous 12 months
• Left ventricular ejection fraction ≤ 50% measured at least 1 time in transthoracic echocardiography in the last 12 months
• Treated by optimal medical therapy (ACE-I or angiotensin receptor blocker or sacubitril-valsartan, and betablockers, and mineralocorticoid receptor antagonist and furosemide) unless such use was contraindicated or previously associated with side-effects leading to drug discontinuation. No change in drugs dosages in the last month.
• Able to give written informed consent
• If female of childbearing potential, have a negative serum pregnancy test
• Use of a validated method of birth control until the end of the study (men and women)
• Affiliation to a social security regime

You may not qualify if:

• Hypersensitivity to dapagliflozin or to any of the excipients
• Current treatment with gliflozine
• Cardiac rhythm disorder including atrial fibrillation \> 100 bpm
• Significant valvular heart disease including mitral or aortic regurgitation \> II/IV
• Hospitalisation for heart failure or unplanned visit for worsening heart failure in the last month
• Recent (last 3 months) or planned coronary revascularization
• Acute coronary syndrome, stroke, or transient ischemic attack in the last 3 months
• Body mass-index \> 40 kg/m2
• Uncontrolled type 2 diabetes (Hb1AC \> 9%) or type 1 diabetes
• Genetic diabetes (Maturity Onset Diabetes of the Young, MODY)
• Current treatment for cancer, cardiotoxic cancer treatment in the last year
• Treatment with systemic steroids at time of informed consent or change in dosage of thyroid hormones in the last 6 weeks
• Active infectious diseases
• Hypovolemia or dehydration, severe hypokalaemia, or severe hyponatremia
• Contraindication to MRI or to contrast agents used

Sponsors & Collaborators

• Assistance Publique - Hôpitaux de Paris: lead

Study Sites (1)

Pitié-Salpêtrière Hospital

Paris, 75013, France

RECRUITING

MeSH Terms

Conditions

Heart Failure; Fibrosis

Interventions

dapagliflozin

Condition Hierarchy (Ancestors)

Heart Diseases; Cardiovascular Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Alban REDHEUIL, MD PhD

  Assistance Publique - Hôpitaux de Paris

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Alban REDHEUIL, MD PhD

CONTACT

+33(0)1.42.16.55.45; alban.redheuil@aphp.fr

Fabrizio ANDREELLI, MD PhD

CONTACT

33(0)1.42.17.80.59; fabrizio.andreelli@aphp.fr

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 12, 2022
• First Posted: June 15, 2022
• Study Start: June 26, 2022
• Primary Completion: September 1, 2023
• Study Completion: May 1, 2024
• Last Updated: December 9, 2022

Record last verified: 2022-02

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: Beginning 3 months and ending 3 years following article publication. Requests out of these time frame can also be submitted to the sponsor
• Access Criteria: Researchers who provide a methodologically sound proposal

Locations

FR (1)