Clinical trial NCT06868797: Acute Reno-Cardiac Action of Dapagliflozin In Advanced Heart Failure Patients on Heart Transplant Waiting List
Official title: Acute Reno-Cardiac Action of Dapagliflozin In Advanced Heart Failure Patients on Heart Transplant Waiting List
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: NA
Conditions: Heart Failure
Lead sponsor: Central Hospital, Nancy, France
Sponsor class: OTHER
First posted: 2025-03-11
Enrollment: 103
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: Prospective cohort study
Primary purpose: OTHER

Brief summary: 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.


Eligibility criteria: 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)

Primary outcomes:
measure: the change in soluble urokinase-type plasminogen activator receptor (suPAR) levels (ng/ml)
timeFrame: baseline and 6 months of follow-up.
Secondary outcomes:
measure: VO2 max
timeFrame: baseline and 6 months of follow-up.
measure: Delta GFR estimated by CKD-EPI formula (ml/min/1.73m²)
timeFrame: baseline and 6 months of follow-up.
measure: Rate of composite outcome (hospitalization for acute heart failure or all cause death).
timeFrame: baseline and 6 months of follow-up.
measure: Quality of life assessed by Kansas City Cardiomyopathy Questionnaire (KCCQ)
timeFrame: baseline and 12 months.
measure: Global Leadership Initiative on Malnutrition criteria (GLIM Criteria)
timeFrame: baseline and 6 months
measure: Daily food and nutrient intake
timeFrame: baseline or the month following baseline
measure: cardiovascular death
timeFrame: 12 months
measure: unplanned hospitalization for Heart failure
timeFrame: 12 months
measure: worsening of Heart failure
timeFrame: 12 months
measure: cardiac transplantation
timeFrame: 12 months
measure: ECMO
timeFrame: 12 months
measure: Left Ventricular Assist Device
timeFrame: 12 months
measure: Delisting from national waiting list
timeFrame: 12 months
measure: renal death
timeFrame: 12 months
measure: chronic dialysis
timeFrame: 12 months
measure: renal transplantation
timeFrame: 12 months
measure: End stage renal disease
timeFrame: 12 months
measure: worsening cardio-renal syndrome
timeFrame: 12 months
measure: GFR estimated by CKD-EPI formula (serum creatinine cystatin or both)
timeFrame: baseline and 6 months
measure: GFR estimated by MDRD formula
timeFrame: baseline and 6 months
measure: iohexol clearance
timeFrame: baseline and 6 months
measure: inuline clearance
timeFrame: baseline and 6 months
measure: EDTA chrome51
timeFrame: baseline and 6 months
measure: Iothalamate clearance
timeFrame: baseline and 6 months
measure: PLAUR gene expression
timeFrame: baseline and 6 months
Other outcomes:
Locations:
city: Bron
country: France
facility: Hospice Civil de Lyon - Hôpital Louis PRADEL
city: La tronche
country: France
facility: CHU Grenoble
city: Montpellier
country: France
facility: CHU Montpellier
city: Nantes
country: France
facility: Chu Nantes
city: Paris
country: France
facility: Aphp Hegp
city: Pessac
country: France
facility: CHU Bordeaux
city: Rennes
country: France
facility: CHU Rennes
city: Rouen
country: France
facility: Chu Rouen
city: Strasbourg
country: France
facility: CHU Strasbourg
city: Toulouse
country: France
facility: CHU de Toulouse
city: Vandoeuvre lès Nancy
country: France
facility: Chru Nancy
Study officials:
affiliation: CHRU de NANCY
name: Nicolas GIRERD, MD-PhD
role: STUDY_CHAIR
References: