Acute Reno-Cardiac Action of Dapagliflozin in Advanced Heart Failure Patients on Heart Transplant Waiting List

Not Applicable

Not yet recruiting

• Conditions: Heart Failure

• Registration Number: NCT06868797
• Lead Sponsor: Central Hospital, Nancy, France

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.

Detailed Description

Not available

Study Timeline

• Status Verified: 2025-02
• Study First Submitted: 2025-02-17
• Study First Submitted QC: 2025-03-04
• Last Update Submitted: 2025-03-04
• Study First Posted: 2025-03-11
• Last Update Posted: 2025-03-11
• Study Start: 2025-03-15
• Primary Completion: 2026-09-15
• Study Completion: 2027-03-15

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 103

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)

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Primary Outcome Measures

Name	Time	Method
the change in soluble urokinase-type plasminogen activator receptor (suPAR) levels (ng/ml)	baseline and 6 months of follow-up.	the change in soluble urokinase-type plasminogen activator receptor (suPAR) levels (ng/ml) between the baseline and 6 months of follow-up.

Secondary Outcome Measures

Name	Time	Method
VO2 max	baseline and 6 months of follow-up.	Functional status at baseline and 6 months assessed by VO2 max assessment
Delta GFR estimated by CKD-EPI formula (ml/min/1.73m²)	baseline and 6 months of follow-up.	The following parameters are collected at baseline to identify predictive factors associated with secondary endpoint. These parameters should not be considered as endpoints themselves: * Hemodynamic Parameters: cardiac output (L/min), pulmonary capillary wedge pressure (mmHg), pulmonary artery systolic and mean pressure (mmHg), right atrial pressure (mmHg).; * Echocardiographic Parameters: LVEF (%), mitral regurgitation grade (0-4), left atrial volume (mL /m2).; * Biological Parameters: Nt-proBNP (ng/L), Creatinine (µmol/L), GFR evaluate by Iohexol clearance (ml/min) or other method (ml/min) (inuline, EDTA chrome51 (51Cr EDTA), Iothalamate clearance),plasma volume calculated from haemoglobin (g/L) and haematocrit,(%) bilirubin (µmol/L), AST (UI/L), ALT (UI/L), kalemia (mmol/L), cystatin C (mg/L), sST2 (ng/mL), gremlins 1(pg/mL), FGF 23 (C terminal and intact) (pg/mL).; * Congestion Markers: Clinical, biological, echocardiographic, and hemodynamic markers.
Rate of composite outcome (hospitalization for acute heart failure or all cause death).	baseline and 6 months of follow-up.	The following parameters are collected at baseline to identify predictive factors associated with secondary endpoint. These parameters should not be considered as endpoints themselves: * Hemodynamic Parameters: cardiac output (L/min), pulmonary capillary wedge pressure (mmHg), pulmonary artery systolic and mean pressure (mmHg), right atrial pressure (mmHg).; * Echocardiographic Parameters: LVEF (%), mitral regurgitation grade (0-4), left atrial volume (mL /m2).; * Biological Parameters: Nt-proBNP (ng/L), Creatinine (µmol/L), GFR evaluate by Iohexol clearance (ml/min) or other method (ml/min) (inuline, EDTA chrome51 (51Cr EDTA), Iothalamate clearance),plasma volume calculated from haemoglobin (g/L) and haematocrit,(%) bilirubin (µmol/L), AST (UI/L), ALT (UI/L), kalemia (mmol/L), cystatin C (mg/L), sST2 (ng/mL), gremlins 1(pg/mL), FGF 23 (C terminal and intact) (pg/mL).; * Congestion Markers: Clinical, biological, echocardiographic, and hemodynamic markers.
Quality of life assessed by Kansas City Cardiomyopathy Questionnaire (KCCQ)	baseline and 12 months.	Kansas City Cardiomyopathy Questionnaire (KCCQ) is a 23-item, self-administered instrument that quantifies physical function, symptoms (frequency, severity and recent change), social function, self-efficacy and knowledge, and quality of life. The KCCQ total symptom score incorporates the symptom domains into a single score. Scores are transformed to a range of 0-100, in which higher scores reflect better health status.
GFR estimated by MDRD formula	baseline and 6 months	To assess the degree of agreement between the different methods of estimating GFR.
Global Leadership Initiative on Malnutrition criteria (GLIM Criteria)	baseline and 6 months	To assess changes in nutritional status according to Global Leadership Initiative on Malnutrition criteria status between Baseline and 6 months. Categories : no malnutrition, moderate malnutrition, or severe malnutrition
cardiovascular death	12 months	To assess incidence of cardiac and renal adverse events.
Left Ventricular Assist Device	12 months	To assess incidence of cardiac and renal adverse events
Delisting from national waiting list	12 months	to assess incidence of cardiac and renal adverse events
renal transplantation	12 months	To assess incidence of cardiac and renal adverse events.
End stage renal disease	12 months	To assess incidence of cardiac and renal adverse events. Chronic dialysis, renal transplantation or sustained eGFR \<15 mL/min/1.73m²
Daily food and nutrient intake	baseline or the month following baseline	The food frequency questionnaire evaluate the frequency of consumption and portion size for 170 foods, we then calculate the daily food intake (in g/day). Nutritrional values are determined by converting food intake into nutrient intake using a french food composition table. Each item can have a minimum intake of 0, with quantities varying based on the specific food and individual consumption.
cardiac transplantation	12 months	To assess incidence of cardiac and renal adverse events
unplanned hospitalization for Heart failure	12 months	To assess incidence of cardiac and renal adverse events. The definition for unplanned heart failure hospitalization requires: 1) a hospital stay for worsening heart failure for \>24 h; and 2) administration of intravenous or mechanical heart failure therapies, especially loop diuretics 3) heart failure symptoms/signs.
worsening of Heart failure	12 months	To assess incidence of cardiac and renal adverse events. The definition for worsening of heart failure requires an administration of loop diuretics intravenous (ambulatory or home-care) due to a worsening of heart failure symptoms/signs.
chronic dialysis	12 months	To assess incidence of cardiac and renal adverse events.
ECMO	12 months	To assess incidence of cardiac and renal adverse events
renal death	12 months	To assess incidence of cardiac and renal adverse events.
iohexol clearance	baseline and 6 months	to assess the degree of agreement between the different methods of estimating GFR
inuline clearance	baseline and 6 months	To assess the degree of agreement between the different methods of estimating GFR
Iothalamate clearance	baseline and 6 months	To assess the degree of agreement between the different methods of estimating GFR
worsening cardio-renal syndrome	12 months	To assess incidence of cardiac and renal adverse events. Worsening cardio-renal syndrome was defined according to the Kidney Disease Improving Global Outcomes (KIDGO) criteria as a ≥ 26.5 µmol/L (0.3mg/dL) increase in serum creatinine or 1.5-1.9 times baseline increase in serum creatinine or a urine output \<0.5 ml/kg/h for 6-12 hours.
GFR estimated by CKD-EPI formula (serum creatinine cystatin or both)	baseline and 6 months	To assess the degree of agreement between the different methods of estimating GFR.
PLAUR gene expression	baseline and 6 months	To assess the change in gene expression (including PLAUR gene) using the RNA collected at baseline and at 6 months.
EDTA chrome51	baseline and 6 months	To assess the degree of agreement between the different methods of estimating GFR

Trial Locations

Locations (11)

Chru Nancy; 🇫🇷 Vandoeuvre lès Nancy, France

Hospice Civil de Lyon - Hôpital Louis PRADEL; 🇫🇷 Bron, France

CHU Grenoble; 🇫🇷 La tronche, France

CHU Montpellier; 🇫🇷 Montpellier, France

Chu Nantes; 🇫🇷 Nantes, France

Aphp Hegp; 🇫🇷 Paris, France

CHU Bordeaux; 🇫🇷 Pessac, France

CHU Rennes; 🇫🇷 Rennes, France

Chu Rouen; 🇫🇷 Rouen, France

CHU Strasbourg; 🇫🇷 Strasbourg, France

CHU de Toulouse; 🇫🇷 Toulouse, France