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

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.

Study Overview

• Status: Recruiting
• Conditions: Heart Failure
• Intervention / Treatment: Other: Biological sample for the measurement of suPAR levels.

• Study Type: Interventional
• Enrollment (Estimated): 103
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Guillaume BAUDRY, MD; Phone Number: +33 (0) 383157322; Email: g.baudry@chru-nancy.fr

Study Locations

• France
  • Bron, France, 69500
    • Not yet recruiting
    • Hospice Civil de Lyon - Hôpital Louis PRADEL
    • Contact: Nathan MEWTON, MD-PhD; Phone Number: +33 (0)4 72 11 80 88; Email: nathan.mewton@chu-lyon.fr
    • Principal Investigator: Nathan MEWTON, MD-PhD
  • La Tronche, France, 38700
    • Not yet recruiting
    • CHU Grenoble
    • Contact: Aude BOIGNARD, MD; Phone Number: +33(0) 476 76 75 75; Email: ABoignard@chu-grenoble.fr
    • Principal Investigator: Aude Boignard, MD
  • Montpellier, France, 34295
    • Not yet recruiting
    • CHU Montpellier
    • Contact: Valentin DUPASQUIER, MD-PhD; Phone Number: +33(0)4 67 33 67 33; Email: valentin.dupasquier@chu-montpellier.fr
    • Principal Investigator: VALENTIN DUPASQUIER, MD-PhD
  • Nantes, France, 44093
    • Not yet recruiting
    • CHU Nantes
    • Contact: Sabine PATTIER, MD-PhD; Phone Number: +33 (0)2 40 08 33 33; Email: sabine.pattier@chu-nantes.fr
    • Principal Investigator: Sabine PATTIER, MD-PhD
  • Paris, France, 75015
    • Not yet recruiting
    • Aphp Hegp
    • Contact: Anne Céline MARTIN, MD-PhD; Phone Number: +33(0)1 56 09 20 00; Email: anne-celine.martin@aphp.fr
    • Principal Investigator: Anne Céline MARTIN, MD-PhD
  • Pessac, France, 33600
    • Not yet recruiting
    • CHU Bordeaux
    • Contact: Maxime FAURE, MD-PhD; Phone Number: +33(0)5 56 79 56 79; Email: maxime.faure@chu-bordeaux.fr
    • Principal Investigator: Maxime FAURE, MD-PhD
  • Rennes, France, 35033
    • Not yet recruiting
    • Chu Rennes
    • Contact: Céline CHABANNES, MD-PhD; Phone Number: +33(0)2 99 28 43 21; Email: Celine.CHABANNE@chu-rennes.fr
    • Principal Investigator: Céline CHABANNES, MD-PhD
  • Rouen, France, 76031
    • Not yet recruiting
    • CHU Rouen
    • Contact: Charles FAUVEL, MD-PhD; Phone Number: +33(0)2 32 88 89 90; Email: Charles.Fauvel@chu-rouen.fr
    • Principal Investigator: Charles FAUVEL, MD-PhD
  • Strasbourg, France, 67091
    • Not yet recruiting
    • CHU Strasbourg
    • Contact: Jean Jacques VON HUNOLSTEIN, MD-PhD; Phone Number: +33(0)3 88 11 67 68; Email: Jean-Jacques.VONHUNOLSTEIN@chru-strasbourg.fr
    • Principal Investigator: Jean Jacques VON HUNOLSTEIN, MD-PhD
  • Toulouse, France, 31059
    • Not yet recruiting
    • CHU de Toulouse
    • Contact: Romain ITIER, MD-PhD; Phone Number: +33(0)5 61 77 22 33; Email: itier.r@chu-toulouse.fr
    • Principal Investigator: Romain ITIER, MD-PhD
  • Vandœuvre-lès-Nancy, France, 54500
    • Recruiting
    • Chru Nancy
    • Contact: Guillaume BAUDRY, MD; Phone Number: +33(0)383157322; Email: g.baudry@chru-nancy.fr
    • Principal Investigator: Guillaume BAUDRY, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Other: Patients followed for end-stage heart failure; 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.

Other: Biological sample for the measurement of suPAR levels.; Biological sample for the measurement of plasminogen activator receptor (suPAR) level at baseline and at 6 months follow up to assess the evolution of cardio-renal interaction in HF patients listed for heart transplant treated by GDMT including dapagliflozin.

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
VO2 max	Functional status at baseline and 6 months assessed by VO2 max assessment	baseline and 6 months of follow-up.
Delta GFR estimated by CKD-EPI formula (ml/min/1.73m²)	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.	baseline and 6 months of follow-up.
Quality of life assessed by Kansas City Cardiomyopathy Questionnaire (KCCQ)	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.	baseline and 12 months.
Global Leadership Initiative on Malnutrition criteria (GLIM Criteria)	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	baseline and 6 months
Daily food and nutrient intake	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.	baseline or the month following baseline
cardiovascular death	To assess incidence of cardiac and renal adverse events.	12 months
unplanned hospitalization for Heart failure	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.	12 months
worsening of Heart failure	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.	12 months
cardiac transplantation	To assess incidence of cardiac and renal adverse events	12 months
ECMO	To assess incidence of cardiac and renal adverse events	12 months
Left Ventricular Assist Device	To assess incidence of cardiac and renal adverse events	12 months
Delisting from national waiting list	to assess incidence of cardiac and renal adverse events	12 months
renal death	To assess incidence of cardiac and renal adverse events.	12 months
chronic dialysis	To assess incidence of cardiac and renal adverse events.	12 months
renal transplantation	To assess incidence of cardiac and renal adverse events.	12 months
End stage renal disease	To assess incidence of cardiac and renal adverse events. Chronic dialysis, renal transplantation or sustained eGFR <15 mL/min/1.73m²	12 months
worsening cardio-renal syndrome	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.	12 months
GFR estimated by CKD-EPI formula (serum creatinine cystatin or both)	To assess the degree of agreement between the different methods of estimating GFR.	baseline and 6 months
GFR estimated by MDRD formula	To assess the degree of agreement between the different methods of estimating GFR.	baseline and 6 months
iohexol clearance	to assess the degree of agreement between the different methods of estimating GFR	baseline and 6 months
inuline clearance	To assess the degree of agreement between the different methods of estimating GFR	baseline and 6 months
EDTA chrome51	To assess the degree of agreement between the different methods of estimating GFR	baseline and 6 months
Iothalamate clearance	To assess the degree of agreement between the different methods of estimating GFR	baseline and 6 months
PLAUR gene expression	To assess the change in gene expression (including PLAUR gene) using the RNA collected at baseline and at 6 months.	baseline and 6 months
Rate of composite outcome (hospitalization for acute heart failure or all cause death).	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.	6 months of follow-up.
urinary creatinine (renal functional assessment (BFR))	To assess the degree of agreement between the different methods of estimating GFR.	baseline and 6 months

Collaborators and Investigators

• Sponsor: Central Hospital, Nancy, France
• Investigators: Study Chair: Nicolas GIRERD, MD-PhD, CHRU de NANCY

Study record dates

Study Major Dates

• Study Start (Actual): August 29, 2025
• Primary Completion (Estimated): February 28, 2027
• Study Completion (Estimated): September 12, 2027

Study Registration Dates

• First Submitted: February 17, 2025
• First Submitted That Met QC Criteria: March 4, 2025
• First Posted (Actual): March 11, 2025

Study Record Updates

• Last Update Posted (Estimated): September 11, 2025
• Last Update Submitted That Met QC Criteria: September 5, 2025
• Last Verified: September 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Heart Diseases; Heart Failure
• Other Study ID Numbers: 2023PI024; 2024-A02450-47 (Other Identifier: ID-RCB)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No