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

Overview

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.

Interventions

• 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.

Primary outcome measures

• the change in soluble urokinase-type plasminogen activator receptor (suPAR) levels (ng/ml) [Time frame: baseline and 6 months of follow-up.]

Secondary outcome measures (12)

• VO2 max [Time frame: baseline and 6 months of follow-up.]
• Delta GFR estimated by CKD-EPI formula (ml/min/1.73m²) [Time frame: baseline and 6 months of follow-up.]
• Rate of composite outcome (hospitalization for acute heart failure or all cause death). [Time frame: 6 months of follow-up.]
• Quality of life assessed by Kansas City Cardiomyopathy Questionnaire (KCCQ) [Time frame: baseline and 12 months.]
• Global Leadership Initiative on Malnutrition criteria (GLIM Criteria) [Time frame: baseline and 6 months]
• Daily food and nutrient intake [Time frame: baseline or the month following baseline]
• cardiovascular death [Time frame: 12 months]
• unplanned hospitalization for Heart failure [Time frame: 12 months]
• worsening of Heart failure [Time frame: 12 months]
• cardiac transplantation [Time frame: 12 months]
• ECMO [Time frame: 12 months]
• Left Ventricular Assist Device [Time frame: 12 months]

Eligibility criteria

Inclusion criteria

• Age ≥ 18 years and ≤ 85 years
• NYHA class ≥3
• LVEF ≤ 35%
• On GDMT (including dapagliflozin) based on current heart failure practice guidelines at maximal tolerated dose
• 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.
• Person affiliated to a social security scheme or beneficiary of such a scheme.
• A person who has received full information about the organization of the clinical research and has signed an informed consent form.

Exclusion criteria

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

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Other

Study locations

France · 11 centers

• Hospice Civil de Lyon - Hôpital Louis PRADEL — Bron
• CHU Grenoble — La Tronche
• CHU Montpellier — Montpellier
• Chu Nantes — Nantes
• Aphp Hegp — Paris
• CHU Bordeaux — Pessac
• CHU Rennes — Rennes
• Chu Rouen — Rouen
• … and 3 more centers

Identifiers

NCT: NCT06868797 · 2023PI024 · 2024-A02450-47

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗