Acute Reno-Cardiac Action of Dapagliflozin In Advanced Heart Failure Patients on Heart Transplant Waiting List (ARCADIA-HF)

Central Hospital, Nancy, France

Status: Enrolling

Conditions: Heart Failure

Treatments: Other: Biological sample for the measurement of suPAR levels.

Study type: Interventional

Funder types: Other

Identifiers

NCT06868797

2023PI024

2024-A02450-47 (Other Identifier)

Details and patient eligibility

About

Heart failure affects 1 to 2% of the adult population in developed countries, representing about 55 million people worldwide.

Advanced heart failure is a condition where the heart can no longer provide sufficient cardiac output or equilibrate pressures within its chambers, leading to symptoms such as shortness of breath, fatigue, and water and salt retention.

Heart failure affects the kidneys by reducing blood flow directed to them, sometimes leading to kidney congestion. In the long term, this can degrade kidney function. Common medications used to treat heart failure, such as diuretics, can sometimes worsen kidney failure. This link between the heart and the kidneys is known as cardio-renal syndrome and requires careful management of both organs to prevent mutual degradation.

Dapagliflozin is an SGLT2 inhibitor medication used to treat type 2 diabetes, heart failure, and certain kidney diseases. It helps reduce blood sugar, improve heart and kidney function, while promoting the elimination of excess salt and water.

However, there are limited data regarding the progression of cardio-renal interactions in patients with advanced heart failure. Yet, advanced heart failure is often associated with kidney dysfunction.

The protein called suPAR is found in the blood of patients developing kidney disease and/or during the onset of acute kidney injury. This protein will allow to characterize a population of patients with advanced heart failure receiving optimized medical treatment, including dapagliflozin.

The main objective of this research is to assess, based on the suPAR protein level in the blood, the progression of cardio-renal damage between inclusion and 6 months in patients with advanced heart failure who are listed for a heart transplant and treated with a therapy including dapagliflozin.

The study plans 5 visits over 12 months. The research will take place in the cardiology department of several French hospitals.

Enrollment: 103 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

1. Age ≥ 18 years and ≤ 85 years
2. NYHA class ≥3
3. LVEF ≤ 35%
4. On GDMT (including dapagliflozin) based on current heart failure practice guidelines at maximal tolerated dose
5. On waiting list (or on the registration pathway) for heart transplantation after multidisciplinary Heart Team decision, with anticipated access to heart transplant ≥ 6 months or in a pre-transplant pathway.
6. Person affiliated to a social security scheme or beneficiary of such a scheme.
7. A person who has received full information about the organization of the clinical research and has signed an informed consent form.

Exclusion criteria

1. Priority patient on waiting list for heart transplantation.
2. Etiology of heart failure due to or associated with uncorrected thyroid disease, obstructive cardiomyopathy, pericardial disease, amyloidosis or restrictive cardiomyopathy.
3. Inotrope dependent, existence of ongoing mechanical circulatory support
4. Current acute decompensated HF or hospitalization due to decompensated HF <30 days prior to the enrolment.
5. History of any organ transplant or prior implantation of a ventricular assistance device (VAD) or similar device, or implantation expected after inclusion.
6. Any recent interventional procedure likely to improve symptoms and heart failure status (coronary revascularization, percutaneous mitral valve intervention, cardiac resynchronization therapy) < 60 days.
7. Glomerular filtration rate <25 ml/min/1.73 m2, according to CKD-EPI formula
8. Unstable or rapidly progressing renal disease (autosomal dominant or autosomal recessive polycystic kidney disease, lupus nephritis or ANCA-associated vasculitis).
9. Type 1 diabetes mellitus.
10. Participation in another clinical interventional trial.
11. Any condition other than heart failure that could limit survival to less than 12 months.
12. Pregnant women or breastfeeding mothers
13. vulnerable persons (guardianship, curatorship, safeguard of justice)

Trial design

Primary purpose: Other

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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103 participants in 1 patient group

Patients followed for end-stage heart failure

Other group

Description:

Patients followed for end-stage heart failure and waiting for heart transplantation. This cohort will focus on cardio-renal assessment of advanced HF patients treated with optimal pharmacologic therapy including dapagliflozin. The biological material and clinical data collected will allow us to better understand the advanced HF and to generate new research hypotheses.

Treatment:

Other: Biological sample for the measurement of suPAR levels.