Acute Reno-Cardiac Action of Dapagliflozin In Advanced Heart Failure Patients on Heart Transplant Waiting List (ARCADIA-HF)
Primary Purpose
End-stage Heart Failure
Status
Withdrawn
Phase
Phase 2
Locations
France
Study Type
Interventional
Intervention
Dapagliflozin 10mg
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for End-stage Heart Failure focused on measuring End-stage heart failure,, Cardio-renal syndrome, Dapagliflozin
Eligibility Criteria
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
Sites / Locations
- Hôpital Pneumologique et Cardiovasculaire Louis Pradel
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
Treatment group Daplagliflozin
Control group
Arm Description
Outcomes
Primary Outcome Measures
Levels of suPAR (ng/ml)
Secondary Outcome Measures
VO2 max assessment
VO2 max assessment to evaluate the functional status
cardiac output assessed by right heart catheterization
The impact of dapagliflozin on hemodynamic parameters between baseline and 6 months assessed by right heart catheterization hemodynamic parameters
pulmonary capillary wedge pressure assessed by right heart catheterization
The impact of dapagliflozin on hemodynamic parameters between baseline and 6 months assessed by right heart catheterization hemodynamic parameters
pulmonary artery systolic and mean pressure assessed by right heart catheterization
The impact of dapagliflozin on hemodynamic parameters between baseline and 6 months assessed by right heart catheterization hemodynamic parameters
mean pressure assessed by right heart catheterization
The impact of dapagliflozin on hemodynamic parameters between baseline and 6 months assessed by right heart catheterization hemodynamic parameters
right atrial pressure assessed by right heart catheterization
The impact of dapagliflozin on hemodynamic parameters between baseline and 6 months assessed by right heart catheterization hemodynamic parameters
Left Ventricular Ejection Function assessed by echocardiography
The impact of dapagliflozin on echocardiographic parameters between baseline and 6 months
Left ventricular end-diastolic diameter assessed by echocardiography
The impact of dapagliflozin on echocardiographic parameters between baseline and 6 months
Left ventricular end systolic volume assessed by echocardiography
The impact of dapagliflozin on echocardiographic parameters between baseline and 6 months
mitral regurgitation grade assessed by echocardiography
The impact of dapagliflozin on echocardiographic parameters between baseline and 6 months
left atrial volume assessed by echocardiography
The impact of dapagliflozin on echocardiographic parameters between baseline and 6 months
Nt-proBNP level
Creatinine level
Quality of life assessed by Kansas City Cardiomyopathy Questionnaire (KCCQ)
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT04782245
Brief Title
Acute Reno-Cardiac Action of Dapagliflozin In Advanced Heart Failure Patients on Heart Transplant Waiting List
Acronym
ARCADIA-HF
Official Title
Acute Reno-Cardiac Action of Dapagliflozin In Advanced Heart Failure Patients on Heart Transplant Waiting List: a Multicenter, Double-blind, Randomized Clinical Trial.
Study Type
Interventional
2. Study Status
Record Verification Date
August 2023
Overall Recruitment Status
Withdrawn
Why Stopped
New recommandations
Study Start Date
September 2022 (Anticipated)
Primary Completion Date
April 2024 (Anticipated)
Study Completion Date
April 2024 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Hospices Civils de Lyon
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
End-stage Heart Failure
Keywords
End-stage heart failure,, Cardio-renal syndrome, Dapagliflozin
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
0 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Treatment group Daplagliflozin
Arm Type
Experimental
Arm Title
Control group
Arm Type
Placebo Comparator
Intervention Type
Drug
Intervention Name(s)
Dapagliflozin 10mg
Intervention Description
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
Intervention Name(s)
Placebo
Intervention Description
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.
Primary Outcome Measure Information:
Title
Levels of suPAR (ng/ml)
Time Frame
6 months
Secondary Outcome Measure Information:
Title
VO2 max assessment
Description
VO2 max assessment to evaluate the functional status
Time Frame
6 months
Title
cardiac output assessed by right heart catheterization
Description
The impact of dapagliflozin on hemodynamic parameters between baseline and 6 months assessed by right heart catheterization hemodynamic parameters
Time Frame
6 months
Title
pulmonary capillary wedge pressure assessed by right heart catheterization
Description
The impact of dapagliflozin on hemodynamic parameters between baseline and 6 months assessed by right heart catheterization hemodynamic parameters
Time Frame
6 months
Title
pulmonary artery systolic and mean pressure assessed by right heart catheterization
Description
The impact of dapagliflozin on hemodynamic parameters between baseline and 6 months assessed by right heart catheterization hemodynamic parameters
Time Frame
6 months
Title
mean pressure assessed by right heart catheterization
Description
The impact of dapagliflozin on hemodynamic parameters between baseline and 6 months assessed by right heart catheterization hemodynamic parameters
Time Frame
6 months
Title
right atrial pressure assessed by right heart catheterization
Description
The impact of dapagliflozin on hemodynamic parameters between baseline and 6 months assessed by right heart catheterization hemodynamic parameters
Time Frame
6 months
Title
Left Ventricular Ejection Function assessed by echocardiography
Description
The impact of dapagliflozin on echocardiographic parameters between baseline and 6 months
Time Frame
6 months
Title
Left ventricular end-diastolic diameter assessed by echocardiography
Description
The impact of dapagliflozin on echocardiographic parameters between baseline and 6 months
Time Frame
6 months
Title
Left ventricular end systolic volume assessed by echocardiography
Description
The impact of dapagliflozin on echocardiographic parameters between baseline and 6 months
Time Frame
6 months
Title
mitral regurgitation grade assessed by echocardiography
Description
The impact of dapagliflozin on echocardiographic parameters between baseline and 6 months
Time Frame
6 months
Title
left atrial volume assessed by echocardiography
Description
The impact of dapagliflozin on echocardiographic parameters between baseline and 6 months
Time Frame
6 months
Title
Nt-proBNP level
Time Frame
6 months
Title
Creatinine level
Time Frame
6 months
Title
Quality of life assessed by Kansas City Cardiomyopathy Questionnaire (KCCQ)
Time Frame
6 months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Guillaume BAUDRY, Dr
Organizational Affiliation
Hospices Civils de Lyon
Official's Role
Principal Investigator
Facility Information:
Facility Name
Hôpital Pneumologique et Cardiovasculaire Louis Pradel
City
Bron
ZIP/Postal Code
69677
Country
France
12. IPD Sharing Statement
Plan to Share IPD
Undecided
Learn more about this trial
Acute Reno-Cardiac Action of Dapagliflozin In Advanced Heart Failure Patients on Heart Transplant Waiting List
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