Cardiometabolic Effects of Dapagliflozin in Heart Failure With Reduced Ejection Fraction

• Status: Not yet recruiting
• Trial end date: 2024-05-01
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Assistance Publique - Hôpitaux de Paris
• Treatments: Dapagliflozin

Criteria

Inclusion Criteria:

• Age ≥ 18 years

• NYHA functional class II-III.

• NT-proBNP > 600 pg/ml (> 400 pg/ml if hospitalized for heart failure in the previous 12 months)

• Left ventricular ejection fraction ≤ 40% measured in transthoracic echocardiography in the 6 last 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.

• Estimated glomerular filtration rate (eGFR) ≥ 30 ml per minute per 1.73 m2 of body-surface area (according to the Modification of Diet in Renal Disease criteria).

• 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

Exclusion Criteria:

• Hypersensitivity to dapagliflozin or to any of the excipients

• Current treatment with gliflozine

• Cardiac rhythm disorder including atrial fibrillation > 60 bpm

• Significant valvular heart disease > II/IV

• Hospitalisation for heart failure or unplanned visit for worsening heart failure in the last 3 months

• Recent (last 6 months) or planned coronary revascularization

• Cardiac resynchronization in the last 6 months

• Acute coronary syndrome, stroke, or transient ischemic attack in the last 2 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)

• Medical history of cancer (other than basal cell carcinoma) and/or treatment for cancer in the last 5 years

• 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

• Left ventricular ejection fraction ≥ 55% measured in the routine transthoracic echocardiography

• Patient on AME (state medical aid)

• Pregnant or breast-feeding female

• Current participation in another interventional study or being in the exclusion period at the end of a previous study

• Patient protected by law (guardianship, tutelage measure, deprived of liberty)