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

NCT ID: NCT04782245

Last Updated: 2023-08-07

Basic Information

• Recruitment Status: WITHDRAWN
• Clinical Phase: PHASE2
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-09-30
• Study Completion Date: 2024-04-30

Brief Summary

In the DAPA-HF trial, the use of dapagliflozin, an inhibitor of sodium-glucose cotransporter 2 (SGLT2), reduced significantly the risk of worsening heart failure or death from cardiovascular causes compared to placebo among patients with heart failure (HF) and a reduced ejection fraction. This new drug offers a very potent and interesting therapeutic pathway since it reduces clinical congestion, it preserves glomerular renal function, does not appear to cause symptomatic clinical hypotension and improves symptoms and quality of life compared to placebo.

Advanced heart failure patients with reduced ejection fraction represent a small and severe subgroup of heart failure of patients with frequent worsening heart failure events and high rates of death. The effect of dapagliflozin in this subgroup of patients was not assessed in the DAPA-HF study. The therapeutic profile of SGLT2 inhibitors appears to be of high interest, since this group of patients has a poor tolerance to usual heart failure drugs, frequent worsening renal function and congestive symptoms persistence with poor quality of life scores.

Soluble urokinase-type plasminogen activator receptor (suPAR) is a signaling glycoprotein considered to be involved in the pathogenesis of kidney disease. It is associated with the risk of acute kidney injury in different clinical and experimental situation. It is also a new validated biomarker predictive of adverse clinical outcome in heart failure patients. This biomarker allows a better risk stratification in heart failure patients after adjustment for Nt-proBNP.

As a useful biomarker implicated in both heart failure and acute kidney injury, suPAR seems to be an interesting biomarker to assess cardio-renal benefits of dapagliflozin.

The aim of this study is to investigate if a treatment by dapagliflozin reduces significantly suPAR compared to placebo in a population of advanced heart failure patients, candidates to heart transplantation. The effect of dapagliflozin compared to placebo will also be assessed on other secondary heart failure outcomes in this patient population.

Conditions

End-stage Heart Failure

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

Treatment group Daplagliflozin

Group Type: EXPERIMENTAL

Dapagliflozin 10mg

Intervention Type: DRUG

The intervention group will receive, during 6 months, dapagliflozin per oral route at a dose of 10 mg once daily in addition to the optimal medical management based on current heart failure practice guidelines.

Control group

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Patients randomized in the control group will receive during 6 months, placebo once daily per oral route, in addition to the optimal medical management based on current heart failure practice guidelines.

Interventions

Dapagliflozin 10mg

The intervention group will receive, during 6 months, dapagliflozin per oral route at a dose of 10 mg once daily in addition to the optimal medical management based on current heart failure practice guidelines.

Intervention Type: DRUG

Placebo

Patients randomized in the control group will receive during 6 months, placebo once daily per oral route, in addition to the optimal medical management based on current heart failure practice guidelines.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

1. Patient has signed informed consent form

2. Age ≥ 18 years

3. NYHA class ≥3

4. LVEF ≤ 35%

5. On optimal medical management (OMM) based on current heart failure practice guidelines at maximal tolerated dose for at least 30 days

6. On waiting list for heart transplantation after multidisciplinary Heart Team decision, with anticipated access to heart transplant ≥ 6 months

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 randomization

6. Presence of an active, uncontrolled infection

7. Any recent interventional procedure likely to improve symptoms and heart failure status (coronary revascularization, percutaneous mitral valve intervention, cardiac resynchronization therapy) < 60 days

8. Glomerular filtration rate < 30 ml/min/1.73 m2, according to CKD-EPI formula

9. Unstable or rapidly progressing renal disease

10. Patients with severe hepatic impairment (Child-Pugh class C)

11. Chronic treatment with dapagliflozin or other SGLT2 inhibitors

12. Patient with known history of severe drug intolerance to dapagliflozin or any excipients of the dapagliflozin (galactose, lactase)

13. Type 1 diabetes mellitus

14. Any surgical or medical condition which might significantly alter the absorption, distribution, metabolism, or extraction of study drug at investigators' discretion

15. Participation in another clinical interventional trial

16. Any condition other than heart failure that could limit survival to less than 24 months

17. Positive pregnancy test if of childbearing potential or refusal to use adequate contraception or women breast-feeding

18. Patients with any legal protection measure

19. Patients without any health coverage

20. Psychiatric disease/disorder, irreversible cognitive dysfunction or psychological issues that are likely to impair compliance

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Hospices Civils de Lyon

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Guillaume BAUDRY, Dr

Role: PRINCIPAL_INVESTIGATOR

Hospices Civils de Lyon

Locations

Hôpital Pneumologique et Cardiovasculaire Louis Pradel

Bron, , France

Countries

France

Other Identifiers

2020-005713-40

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

69HCL20_1135

Identifier Type: -

Identifier Source: org_study_id