- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT04782245
Acute Reno-Cardiac Action of Dapagliflozin In Advanced Heart Failure Patients on Heart Transplant Waiting List (ARCADIA-HF)
Acute Reno-Cardiac Action of Dapagliflozin In Advanced Heart Failure Patients on Heart Transplant Waiting List: a Multicenter, Double-blind, Randomized Clinical Trial.
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.
Study Overview
Status
Conditions
Intervention / Treatment
Study Type
Phase
- Phase 2
Contacts and Locations
Study Locations
-
-
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Bron, France, 69677
- Hôpital Pneumologique et Cardiovasculaire Louis Pradel
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Description
Inclusion Criteria:
- Patient has signed informed consent form
- Age ≥ 18 years
- NYHA class ≥3
- LVEF ≤ 35%
- On optimal medical management (OMM) based on current heart failure practice guidelines at maximal tolerated dose for at least 30 days
- On waiting list for heart transplantation after multidisciplinary Heart Team decision, with anticipated access to heart transplant ≥ 6 months
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 randomization
- Presence of an active, uncontrolled infection
- 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 < 30 ml/min/1.73 m2, according to CKD-EPI formula
- Unstable or rapidly progressing renal disease
- Patients with severe hepatic impairment (Child-Pugh class C)
- Chronic treatment with dapagliflozin or other SGLT2 inhibitors
- Patient with known history of severe drug intolerance to dapagliflozin or any excipients of the dapagliflozin (galactose, lactase)
- Type 1 diabetes mellitus
- Any surgical or medical condition which might significantly alter the absorption, distribution, metabolism, or extraction of study drug at investigators' discretion
- Participation in another clinical interventional trial
- Any condition other than heart failure that could limit survival to less than 24 months
- Positive pregnancy test if of childbearing potential or refusal to use adequate contraception or women breast-feeding
- Patients with any legal protection measure
- Patients without any health coverage
- Psychiatric disease/disorder, irreversible cognitive dysfunction or psychological issues that are likely to impair compliance
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Triple
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Placebo Comparator: Control group
|
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.
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Experimental: Treatment group Daplagliflozin
|
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.
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
Levels of suPAR (ng/ml)
Time Frame: 6 months
|
6 months
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
VO2 max assessment
Time Frame: 6 months
|
VO2 max assessment to evaluate the functional status
|
6 months
|
cardiac output assessed by right heart catheterization
Time Frame: 6 months
|
The impact of dapagliflozin on hemodynamic parameters between baseline and 6 months assessed by right heart catheterization hemodynamic parameters
|
6 months
|
pulmonary capillary wedge pressure assessed by right heart catheterization
Time Frame: 6 months
|
The impact of dapagliflozin on hemodynamic parameters between baseline and 6 months assessed by right heart catheterization hemodynamic parameters
|
6 months
|
pulmonary artery systolic and mean pressure assessed by right heart catheterization
Time Frame: 6 months
|
The impact of dapagliflozin on hemodynamic parameters between baseline and 6 months assessed by right heart catheterization hemodynamic parameters
|
6 months
|
mean pressure assessed by right heart catheterization
Time Frame: 6 months
|
The impact of dapagliflozin on hemodynamic parameters between baseline and 6 months assessed by right heart catheterization hemodynamic parameters
|
6 months
|
right atrial pressure assessed by right heart catheterization
Time Frame: 6 months
|
The impact of dapagliflozin on hemodynamic parameters between baseline and 6 months assessed by right heart catheterization hemodynamic parameters
|
6 months
|
Left Ventricular Ejection Function assessed by echocardiography
Time Frame: 6 months
|
The impact of dapagliflozin on echocardiographic parameters between baseline and 6 months
|
6 months
|
Left ventricular end-diastolic diameter assessed by echocardiography
Time Frame: 6 months
|
The impact of dapagliflozin on echocardiographic parameters between baseline and 6 months
|
6 months
|
Left ventricular end systolic volume assessed by echocardiography
Time Frame: 6 months
|
The impact of dapagliflozin on echocardiographic parameters between baseline and 6 months
|
6 months
|
mitral regurgitation grade assessed by echocardiography
Time Frame: 6 months
|
The impact of dapagliflozin on echocardiographic parameters between baseline and 6 months
|
6 months
|
left atrial volume assessed by echocardiography
Time Frame: 6 months
|
The impact of dapagliflozin on echocardiographic parameters between baseline and 6 months
|
6 months
|
Nt-proBNP level
Time Frame: 6 months
|
6 months
|
|
Creatinine level
Time Frame: 6 months
|
6 months
|
|
Quality of life assessed by Kansas City Cardiomyopathy Questionnaire (KCCQ)
Time Frame: 6 months
|
6 months
|
Collaborators and Investigators
Sponsor
Investigators
- Principal Investigator: Guillaume BAUDRY, Dr, Hospices Civils de Lyon
Study record dates
Study Major Dates
Study Start (Estimated)
Primary Completion (Estimated)
Study Completion (Estimated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- 69HCL20_1135
- 2020-005713-40 (EudraCT Number)
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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